Comprehensive analysis of lncRNA-mRNA co-expression patterns identifies immune-associated lncRNA biomarkers in ovarian cancer malignant progression.
Ovarian cancer (OV) is the most common and lethal gynecological tumor with a poor prognosis for women; however, the regulatory roles of the long non-coding RNAs (lncRNAs) in ovarian malignant progression are insufficiently understood. Here, we investigated the expression patterns of lncRNAs and mRNAs in the high-throughput molecular profiles of 399 OV patients and constructed a functional lncRNA-mRNA co-expression network across OV malignant progression. We found that two protective lncRNAs, RP11-284N8.3.1 and AC104699.1.1, were not only differentially expressed throughout the progression of malignant OV but were also independently predictive of the survival of patients with different OV stages. A functional analysis of the two lncRNAs predicted their roles in immune system activation and other anti-tumor processes in the OV microenvironment. Integrating these two lncRNAs into an OV risk model was able to significantly stratify patients into different risk groups. Overall, our analysis effectively provides insights into the lncRNA association with malignant OV progression. The two-lncRNA signature is a candidate biomarker for the prognosis of patients with OV and may enable a more accurate prediction of survival.


Fermentative production of the unnatural amino acid L-2-aminobutyric acid based on metabolic engineering.
L-2-aminobutyric acid (L-ABA) is an unnatural amino acid that is a key intermediate for the synthesis of several important pharmaceuticals. To make the biosynthesis of L-ABA environmental friendly and more suitable for the industrial-scale production. We expand the nature metabolic network of Escherichia coli using metabolic engineering approach for the production of L-ABA. In this study, Escherichia coli THR strain with a modified pathway for threonine-hyperproduction was engineered via deletion of the rhtA gene from the chromosome. To redirect carbon flux from 2-ketobutyrate (2-KB) to L-ABA, the ilvIH gene was deleted to block the L-isoleucine pathway. Furthermore, the ilvA gene from Escherichia coli W3110 and the leuDH gene from Thermoactinomyces intermedius were amplified and co-overexpressed. The promoter was altered to regulate the expression strength of ilvA* and leuDH. The final engineered strain E. coli THR ΔrhtAΔilvIH/Gap-ilvA*-Pbs-leuDH was able to produce 9.33 g/L of L-ABA with a yield of 0.19 g/L/h by fed-batch fermentation in a 5 L bioreactor. This novel metabolically tailored strain offers a promising approach to fulfill industrial requirements for production of L-ABA.


Periodontal inflammation recruits distant metastatic breast cancer cells by increasing myeloid-derived suppressor cells.
Periodontal diseases can lead to chronic inflammation affecting the integrity of the tooth supporting tissues. Recently, a striking association has been made between periodontal diseases and primary cancers in the absence of a mechanistic understanding. Here we address the effect of periodontal inflammation (PI) on tumor progression, metastasis, and possible underlining mechanisms. We show that an experimental model of PI in mice can promote lymph node (LN) micrometastasis, as well as head and neck metastasis of 4T1 breast cancer cells, both in early and late stages of cancer progression. The cervical LNs had a greater tumor burden and infiltration of MDSC and M2 macrophages compared with LNs at other sites. Pyroptosis and the resultant IL-1β production were detected in patients with PI, mirrored in mouse models. Anakinra, IL-1 receptor antagonist, limited metastasis, and MDSC recruitment at early stages of tumor progression, but failed to reverse established metastatic tumors. PI and the resulting production of IL-1β was found to promote CCL5, CXCL12, CCL2, and CXCL5 expression. These chemokines recruit MDSC and macrophages, finally enabling the generation of a premetastatic niche in the inflammatory site. These findings support the idea that periodontal inflammation promotes metastasis of breast cancer by recruiting MDSC in part by pyroptosis-induced IL-1β generation and downstream CCL2, CCL5, and CXCL5 signaling in the early steps of metastasis. These studies define the role for IL-1β in the metastatic progression of breast cancer and highlight the need to control PI, a pervasive inflammatory condition in older patients.


Intra-arterial injection of Diclofenac by informal health practitioner: A rare complication of a common drug.
Intra-arterial injections (IA) though rare, cause acute limb ischaemia with often catastrophic outcomes. Symptoms could progress rapidly and early identification and intervention could help in preventing the limb gangrene. The work has been reported in line with the SCARE 2020 criteria:Agha RA, Franchi T, Sohrabi C, Mathew G, for the SCARE Group. The SCARE 2020 Guideline: Updating Consensus Surgical CAse REport (SCARE) Guidelines, International Journal of Surgery 2020; 84:226-230. Operative procedure was performed by consultant of general surgery. 38-year-old male presented to surgery casualty with history of sudden onset of pain and paraesthesia in the left forearm and palm followed by progressive weakness and discolouration, 15 hours following injection of Diclofenac in the mid cubital region. On examination, limb temperature was lower, finger movements were minimal. However, distal pulses were palpable, and duplex ultrasound showed normal triphasic flow. In view of the equivocal clinico-radiological findings, the patient underwent CT-Angiography of upper limb, which showed non-opacification of radial and ulnar arteries. Fasciotomy of forearm, brachial artery exploration and removal of embolus was attempted in a doubtful viable left upper limb. No thrombus was noted. Subsequently, he was managed conservatively, and cervical sympathectomy was done. As there was progressive deterioration in the viability of the limb, the patient underwent an above elbow amputation. Intra-arterial injections can lead to limb threatening gangrene, the course of which can be rapid A multidisciplinary team approach was necessary to arrive at a diagnosis and provide optimum care.


Molecular epidemiologic investigation of Polish avian Pasteurella multocida strains isolated from fowl cholera outbreaks showing restricted geographical and host-specific distribution.
Molecular epidemiologic analyses of the 42 clinical isolates of Pasteurella multocida from various avian hosts (geese, ducks, turkeys, and laying hens) in Poland from 2001 to 2011, including a single reference strain, were performed by enterobacterial repetitive intergenic consensus (ERIC)-PCR, single primer PCR, and repetitive extragenic palindromic (REP)-PCR. Forty-two isolates were identified as P. multocida (serotype A). The majority of P. multocida strains were obtained from waterfowl clustered within one genotype, and they were not consistent with the genotypes obtained from the turkey strains. Pasteurella multocida showed genetic homogeneity between the host species, especially when isolated on the same farm. Some of the clones also were characteristic to the particular farm. The strains obtained in different regions represent distinct molecular patterns. The present findings demonstrate that some clones of P. multocida are restricted in geographical and host distribution. In addition, this study suggests that ERIC-PCR, single primer PCR, and REP-PCR are suitable techniques for studying the host adaptation of P. multocida and the epidemiology of fowl cholera.


Genetic polymorphism of fatty acid binding protein-2 in hyperlipidemic Asian Indians in North India.
Fatty acid binding protein-2 (FABP-2) is involved in the metabolism of lipids in the intestine. FABP-2 Ala54Thr polymorphism involves a transition of G to A at codon 54 of FABP-2, resulting in an amino acid substitution Ala54 to Thr54 and is associated with elevated fasting triglycerides in some hyperlipidemic populations. In current genome builds and gene databases the variant of the Ala54Thr FABP-2 (rs 1 799 883) is annotated as c.163A>G (p. Thr55Ala). The status of this polymorphism in hyperlipidemic Asian Indians from North India has not been investigated. This study was aimed to evaluate the distribution of the polymorphic variants of the Ala54Thr FABP-2 and their association with lipids in hyperlipidemic subjects. Ala54Thr FABP-2 polymorphism in both hyperlipidemic (n = 210) and normolipidemic (n = 342) subjects was assessed by PCR-RFLP. Ala54Thr genotypes and alleles distribution did not differ between the hyperlipidemic and normolipidemic groups. The heterozygous genotype FABP-2 Ala/Thr was significantly associated with higher levels of triglycerides and very low-density lipoproteins as compared to the homozygous variant (Thr/Thr) genotype and the wild type homozygous (Ala/Ala) genotype. The heterozygous genotype FABP-2 Ala54Thr is a risk factor for the development of hypertriglyceridemia and increased levels of VLDL-c in Asian Indians from North India.


Serum, interstitial and sweat ATP in humans exposed to heat stress: Insights into roles of ATP in the heat loss responses.
Hyperthermia increases intravascular adenosine triphosphate (ATP) and is associated with greater hyperthermia-induced cutaneous vasodilation. Hyperthermia may also increase skin interstitial fluid ATP thereby activating cutaneous vascular smooth muscle cells and sweat glands. We evaluated the hypothesis that whole-body heating would increase skin interstitial fluid ATP, and this response would be associated with an increase in cutaneous vasodilation and sweating. Nineteen (8 females) young adults underwent whole-body heating using a water-perfusion suit to increase core temperature by ~1°C during which time cutaneous vascular conductance (CVC, ratio of laser-Doppler blood flow to mean arterial pressure) and sweat rate (ventilated capsule technique) were measured at four forearm skin sites to minimize between-site variations. Dialysate from the skin sites were collected via intradermal microdialysis. Heating increased serum ATP, CVC, and sweat rate (all p ≤ 0.031). However, heating did not modulate dialysate ATP (median, baseline vs. end-heating: 2.38 vs. 2.70 nmol/ml) (p = 0.068), though the effect size was moderate (Cohen's d = 0.566). While the heating-induced increase in CVC was not correlated with changes in serum ATP (r = 0.439, p = 0.060), we observed a negative correlation (rs = -0.555, p = 0.017) between dialysate ATP and CVC. We did not observe a significant correlation between the heating-induced sweating and serum, dialysate, or sweat ATP (rs = 0.091 to -0.322, all p ≥ 0.222). Altogether, we showed that passive heating increases ATP in blood and possibly skin interstitial fluid, with the latter potentially blunting cutaneous vasodilation. However, ATP does not appear to modulate sweating.


Coverage in the National Health Service Breast Screening Programme, 1996-2005: correcting for the first invitation of women between 50 and 52 years.
Coverage measures the ability of the National Health Service Breast Screening Programme (NHSBSP) to reach the eligible population and has a target of 70%. To estimate coverage accurately for women aged 50-64. Routine data from the KC63 return were used to calculate coverage for women aged 50-64 using an adjusted method that allows for the fact that women receive a first invitation to screening between 50 and 52.9 years. The adjusted average coverage between 1996 and 2005, for women aged 50-64 was 74.3% and the standard unadjusted average measure for the same period was 68.3%. Therefore, previous measures of coverage for this age group have underestimated coverage by approximately 9% and the adjusted figure is actually well above the target. In terms of coverage the programme has been performing better than previously reported. It is important to monitor the effect of an increasing workload on the programmes ability to re-invite women within three years of their last screen as maintaining coverage is an important factor in ensuring that the NHSBSP is effective in reducing mortality from breast cancer.


Development of high-performance and rapid immunoassay for model food allergen lysozyme using antibody-conjugated bacterial magnetic particles and fully automated system.
A high-performance and rapid chemiluminescence immunoassay for model food allergen lysozyme, one of the major allergenic components in egg white, using antibody-conjugated bacterial magnetic particles and a fully automated system was developed. This system contains a reaction station, tip rack, and an eight-tip pipettor that is able to attach and detach a strong magnet to the tip surface. The immunoreaction time was shortened to 5 min, and the assay was completed within 20 min. The lower detection limit for lysozyme was 10 ng/mL. This system can be used to perform 24 samples in 60 min within 10% coefficient of variation.


Extracting 3D structure from disparity.
The neural mechanisms of stereoscopic 3D shape perception have only recently been investigated. Here we review the two cortical regions in which these mechanisms have been studied so far in macaques: a small subpart of inferotemporal cortex called TEs, and the caudal intraparietal (CIP) region. Neurons in TEs respond selectively to the orientation and curvature in depth of stereoscopic surfaces and this region provides a detailed 3D shape description of surface boundaries and surface content. This description is evoked only by binocular stimuli in which subjects see depth and it does not vary if depth is specified by different cues. Neurons in CIP are a selective for orientation in depth of surfaces and elongated objects, and their responses are also unaffected by changes in depth cues. Thus, stereoscopic 3D shape is processed in both the dorsal, occipito-parietal and the ventral, occipito-temporal streams.


Degradation of fibrinogen by tissue plasminogen activator. Consequences for fibrin polymerization.
In patients treated with tissue plasminogen activator (t-PA), there was a marked increase in concentration of fibrinopeptide A (fpA). The purpose of this study was to analyse the activation of coagulation in plasma treated in vitro by pharmacological doses of t-PA. From our results, it appears that fpA release due to direct interaction of fibrinogen with t-PA, in the absence of plasminogen, is very low and not observed with pharmacological doses of t-PA. In contrast in the presence of plasminogen, the release of fpA is much higher and induces fibrin formation concomitantly to fibrinogen degradation.


Relation of EEG spectrum progression to loss of responsiveness during induction of anesthesia with propofol.
Our purpose is to find out whether the Loss of obeying a Verbal Command (LVC) and the preceding progression of the EEG frequency patterns are mutually related during an anesthetic induction. EEG was analyzed from sixteen patients, anesthetized with a fixed rate infusion of propofol (30 mg/kg/h). An artifact-purified EEG from electrode Fz referenced to the average of mastoid signals was filtered to consecutive 4 Hz frequency passbands with a filter bank. Signal envelope time-series were computed for all the passbands and studied as a function of the elapsed induction time t and as a function of the relative time r, which is t divided by the time of the LVC. A frequency band specific biphasic activity pattern progressed from high towards low frequencies systematically and uniformly in the population studied when presented on the relative time scale r, irrespective of individual responses to the dosage. The grouping of the individual progression patterns on the r scale indicates a strong relation between the EEG spectral behavior and the LVC. EEG may provide phenomenological grounds for a continuous control variable of a sedative drug effect, even in between the discrete clinical end-points.


Maternal fish and shellfish intake and pregnancy outcomes: a prospective cohort study in Brittany, France.
Recommendations about risks and benefits of seafood intake during pregnancy have been published in the last decade, but the specific health effects of the different categories of seafood remain unknown. Fish and shellfish may differ according to their fatty acid content and their concentration of chemical pollutants and toxins. Not taking these particularities into account may result in underestimating of both the positive and negative effects of seafood on birth outcomes and partly explains inconsistent results on the subject. In the PELAGIE cohort study, including 2398 pregnant women from Brittany, we fit multiple linear and logistic regression models to examine associations of fish (salt-water fish only) and shellfish intake before pregnancy with length of gestation, birthweight, and risks of preterm births, low birthweight or small-for-gestational-age (SGA) babies. When fish and shellfish consumptions were considered simultaneously, we observed a decrease in the risk of SGA birth with increasing frequency of fish intake: OR = 0.57 (95%CI: 0.31 to 1.05) for women eating fish twice a week or more compared with those eating it less than once a month. The risk of SGA birth was significantly higher among women eating shellfish twice a week or more than among those eating it less than once a month: OR = 2.14 (95%CI: 1.13 to 4.07). Each additional monthly meal including fish was significantly related to an increase in gestational length of 0.02 week (95%CI: 0.002 to 0.035). No association was observed with birthweight or preterm birth. These results suggest that different categories of seafood may be differently associated with birth outcomes, fish consumption with increased length of gestation and shellfish consumption with decreased fetal growth.


Topological band transition between hexagonal and triangular lattices with (px,py) orbitals.
By combining tight-binding modelling with density functional theory based first-principles calculations, we investigate the band evolution of two-dimensional (2D) hexagonal lattices with (px,py) orbitals, focusing on the electronic structures and topological phase transitions. The (px,py)-orbital hexagonal lattice model possesses two flat bands encompassing two linearly dispersive Dirac bands. Breaking the A/B sublattice symmetry could transform the model into two triangular lattices, each featuring a flat band and a dispersive band. Inclusion of the spin-orbit coupling and magnetization may give rise to quantum spin Hall and quantum anomalous Hall (QAH) states. As a proof of concept, we demonstrate that half-hydrogenated stanene is encoded by a triangular lattice with (px,py) orbitals, which exhibits ferromagnetism and QAH effect with a topological gap of ∼0.15 eV, feasible for experimental observation. These results provide insights into the structure-property relationships involving the orbital degree of freedom, which may shed light on future design and preparation of 2D topological materials for novel electronic/spintronic and quantum computing devices.


Permeability and mechanism of albumin, cationized albumin, and glycosylated albumin transcellular transport across monolayers of cultured bovine brain capillary endothelial cells.
We have measured the permeability and binding characteristics of bovine serum albumin (BSA), cationized BSA (cBSA), and glycosylated BSA (gBSA) to primary cultures of bovine brain capillary endothelial cells (BBCEC). These endothelial cells serve as an in vitro model to study the binding, uptake, and transcellular transport of small and large molecule flux across the blood-brain barrier. The rate of [3H]BSA flux across the cultured BBCEC monolayers grown onto polycarbonate membranes (5-microns pore size) was linear with increasing BSA concentration and the flux could be inhibited by temperature reduction to 0-4 degrees C. The maximal binding of [3H]BSA was 0.04 fmol/mg total cell protein and could not be inhibited by nonradiolabeled BSA. The binding of cBSA and gBSA was rapid and could be inhibited by nonradiolabeled cBSA or gBSA, respectively. The maximal amount bound was 1.8 fmol/mg total cell protein for cBSA and 17.4 fmol/mg total cell protein for gBSA. The dissociation constants (Kd's) were 27 +/- 13 and 3.7 +/- 1.1 nM for cBSA and gBSA, respectively. The flux rates of cBSA and gBSA across the endothelial cell monolayers were linear with respect to concentration and they were approximately seven times greater than those observed for BSA. Each of the proteins appeared on the antiluminal side of the endothelial cell monolayers primarily (90%) as intact protein as determined by trichloroacetic acid (TCA) precipitations and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE). The results for BSA are similar to those observed for lucifer yellow, a fluid-phase endocytic marker.(ABSTRACT TRUNCATED AT 250 WORDS)


GSK2245035, a TLR7 agonist, Does Not Increase Pregnancy Loss in Cynomolgus Monkeys.
GSK2245035, a small molecule Toll-like Receptor 7 (TLR7) agonist developed for immunomodulatory treatment for allergic airways disease, aimed to reduce Th2 and enhance Th1/Treg responses to aeroallergens via the local induction of type I interferons (IFNs). GSK2245035 demonstrated selectivity for potent release of type I IFNs compared to TNF-α and IL-6, with dose dependent increases in the interferon inducible chemokine, IP-10, in the nasal compartment. Implantation and parturition require pro-inflammatory processes including IFNs, Interferon Stimulated Genes, TNFα and IP-10 while pregnancy requires immune regulation to maintain maternal fetal immune tolerance, and recombinant type I IFNs induced abortions in monkeys. Due to its mechanism of action, GSK2245035 was studied at pharmacologically and clinically relevant doses in a monkey pregnancy model. Monkeys received 0, 3 or 30 ng/kg/week GSK2245035 intranasally once weekly, from Day 20 postcoitum through Day 63 postpartum. Although systemic IFN-α and IP-10 levels were approximately 14.8 or 40 -fold (respectively) above predose levels at 3 or 30 ng/kg/week, respectively, there were no effects on pregnancy and infant outcome. Non-adverse effects included increased incidence of nasal discharge, increased maternal body temperature at 30 ng/kg/week and dose-dependent increases in maternal IP-10 and IFN-α and decreased infant anti-KLH IgM and IgG titers following KLH immunization at ≥3 ng/kg/week, relative to controls. Potentially, lower IFN-α and IP-10 levels as well as once-weekly intranasal dosing vs daily subcutaneous or intramuscular dosing with recombinant type I IFNs could explain the lack of pregnancy effects; however, there was an undesired impact on offspring immune function.


Urologic applications of a permanent, epithelializing urethral endoprosthesis.
Recently, a flexible, self-expanding, permanent endoprosthesis has been developed to maintain patency of stenotic arteries after balloon angioplasty. This device, known as the UroLume Wallstent, is now under active investigation in both Europe and the United States as a treatment for: (1) recurrent bulbar urethral strictures, (2) benign prostatic hyperplasia, and (3) detrusor-external sphincter dyssynergia. Preliminary data demonstrate this device to be an effective treatment for all three indications in select patients and to be associated with minimal untoward effects. If the long-term results are equally encouraging, this unique endoprosthesis will represent a significant advancement for the field of urology.


Surgery for intractable epilepsy after severe encephalopathy with reversible splenial lesion and new onset hippocampal lesion associated with parechovirus.
We describe a case of severe encephalopathy with reversible splenial lesion associated with parechovirus, followed by intractable temporal lobe epilepsy (TLE), which was improved by epilepsy surgery. A 3-year-old girl was admitted because of fever, consciousness disturbance and generalized tonic clonic seizure. Her seizure lasted for four hours. Fluid-attenuated inversion recovery (FLAIR) showed a hyperintensity in the splenium of the corpus callosum. Electroencephalogram (EEG) demonstarated continuous diffuse epileptic activity represented by synchronous and rhythmic high-amplitude spikes and waves, which led to the diagnosis of status epilepticus. Her consciousness was improved with fosphenytoin, midazolam and methylprednisolone pulse after 3 days. Seven days later, FLAIR hyperintensity in the splenium of the corpus callosum was disappeared; however, a hyperintensity in the right hippocampus was detected. Since the stool examination was positive for parechovirus, her final diagnosis was reversible splenial lesion syndrome (RESLES) associated with parechovirus. At age 8, she experienced epigastric sensation and consciousness disturbance once a week. Based on the scalp EEG and radiological findings, she was diagnosed with intractable right TLE. We performed a right selective amygdalohippocampectomy and anterior temporal disconnection at 10 years of age. One year and 3 months after surgery, she was seizure free. To our knowledge, this is the first report of severe febrile epilepticus status. with RESLES associated with parechovirus, followed by intractable TLE, which was resolved by epilepsy surgery.


Inhibition of cyclooxygenase-2 prevents adverse effects induced by phosphodiesterase type 4 inhibitors in rats.
Phosphodiesterase type 4 (PDE4) inhibitors such as roflumilast are currently being developed as anti-inflammatory treatments for chronic airway disorders. However, high doses of PDE4 inhibitors have also been linked to several side effects in different animal species, including pro-inflammatory effects in the rat. Here, we analysed PDE4-related toxicological findings in a rat model and how these side effects might be therapeutically prevented. Wistar rats were treated orally once daily with 10 mg·kg⁻¹ roflumilast for 4 days. Macroscopic changes were monitored throughout the study and further parameters were analysed at the end of the experiment on day 5. In addition, the effects of concomitant treatment with cyclooxygenase (COX) inhibitors were assessed. Supratherapeutical treatment with roflumilast induced marked body and spleen weight loss, diarrhea, increased secretory activity of the harderian glands, leukocytosis, increased serum cytokine-induced neutrophil chemoattractant-1 (CINC-1) levels, and histopathological changes in thymus, spleen, mesentery and mesenteric lymph nodes. All these toxicological findings could be prevented by the non-steroidal anti-inflammatory drug (NSAID) and non-selective COX inhibitor, diclofenac, given orally. Similar protective effects could be achieved by the COX-2 selective inhibitor lumiracoxib, whereas the COX-1 selective inhibitor SC-560 was generally not effective. Treatment with an NSAID inhibiting COX-2 prevents the major effects found after subchronic overdosing with the PDE4-specific inhibitor roflumilast. If this effect translates into humans, such combined treatment may increase the therapeutic window of PDE4 inhibitors, currently under clinical development.


The effects of biochar on antibiotic resistance genes (ARGs) removal during different environmental governance processes: A review.
Antibiotic resistance genes (ARGs) pollution has been considered as one of the most significant emerging environmental and health challenges in the 21st century, many efforts have been paid to control the proliferation and dissemination of ARGs in the environment. Among them, the biochar performs a positive effect in reducing the abundance of ARGs during different environmental governance processes and has shown great application prospects in controlling the ARGs. Although there are increasing studies on employing biochar to control ARGs, there is still a lack of review paper on this hotspot. In this review, firstly, the applications of biochar to control ARGs in different environmental governance processes were summarized. Secondly, the processes and mechanisms of ARGs removal promoted by biochar were proposed and discussed. Then, the effects of biochar properties on ARGs removal were highlighted. Finally, the future prospects and challenges of using biochar to control ARGs were proposed. It is hoped that this review could provide some new guidance for the further research of this field.


Effect of host resistance on the feeding and reproductive performance of Haemaphysalis punctata and Ixodes ricinus ticks.
A study was made to assess the influence of host response on Haemaphysalis punctata and Ixodes ricinus biology by comparing the effects of feeding ticks on previously uninfested hosts with those fed on previously sensitised hosts. Adult H punctata were fed on sheep; larvae and nymphs of H punctata and I ricinus were fed on rabbits. The engorgement weights of all instars studied that fed on sensitised hosts fell very gradually with successive infestations. These weight reductions were greater at high than at low levels of infestation. In previously sensitised hosts, the engorgement period of all instars was prolonged: the percentage of instars which completed engorgement and engorgement weights were reduced. The host's clinical and immune response markedly affected the fecundity of adult female ticks and the viability and hatchability of the laid eggs. Eighty per cent of female H punctata successfully laid eggs following the first infestation and the hatchability of eggs was 85 per cent. The numbers successfully laying eggs decreased to 60 per cent during the fifth and sixth infestations and was less than 20 per cent following the seventh infestation; the hatchability decreased similarly. There was no marked effect on the development of immature instars when fed on sensitised rabbits.


Eco-geological consequences of textile processing wastes: Risk assessment, elemental dissolution kinetics, and health hazard potential.
Although substantial quantities of toxic wastes are generated from textile industries, the characteristics of textile processing wastes (TPWs) have yet scantily been investigated from ecological and agricultural perspectives. Here, the eco-geological consequences of TPWs are evaluated by considering three types of sludges (i.e., silk fibre sludge (SFS), dye mixed silk processing sludge (DSPS), and cotton processing wastewater sludge (CPWS)). The predominance of certain components between different wastes (e.g., fibrous substances in silk industry wastes (i.e., SFS and DSPS) and amorphous materials in cotton processing wastes (i.e., CPWS)) is accounted for by the use of different raw materials in different industries. According to the FTIR and other characterization analyses, all three types of TPWs were rich in carbonaceous compounds and nutrients (e.g., CNPK) because of their biological origin. Further, high accumulation of toxic metals (e.g., Cd, Cr, Cu, Zn, Pb, and Mn) was apparent with chemical-processing routes. The principal component analysis indicated strong relationships between certain environmental variables (e.g., moisture content and bulk density) and bioavailability of several metals (e.g., Cd, Zn, Cu, and Mn), while C levels in TPWs were tightly associated with Cr levels. According to the Visual MINTEQ model, the dissolution-precipitation dynamics of potentially toxic elements (e.g., Pb, Cr, and Zn) in TPWs are predicted to be controlled by the levels of phosphates/chlorides/sulphates in line with the textile processing steps employed in different factories. The great toxicity potential of CPWS (e.g., relative to SFS and DSPS) is recognized to pose significant metal-induced hazards to ecosystems and human health over time. Among the three TPWs, SFS could be prescribed for agricultural application after proper treatment (e.g., via valorization techniques) with the aid of its benign nature and high nutrient (Total N: 3.83%; available P: 118.6 mg kg-1) value.


Research directions for bone healing.
Recently our knowledge has vastly expanded in the pathophysiological mechanisms governing the healing process of fractures. Research is ongoing in every aspect of tissue engineering and regeneration. Several molecular mediators have entered phase III clinical trials in order to evaluate their efficacy in enhancing the biological activity of fractures. Despite these developments several issues of importance remain obscured. For instance the timing of intervention, the appropriate dose of agents, the length of intervention, the routine use of available growth factors in clinical practice or not represent some of the important areas requiring further investigation. This article highlights issues relating to bone regeneration which could potentially be the focus of research in the near future.


Methods for studying unconscious learning.
One has to face numerous difficulties when trying to establish a dissociation between conscious and unconscious knowledge. In this paper, we review several of these problems as well as the different methodological solutions that have been proposed to address them. We suggest that each of the different methodological solutions offered refers to a different operational definition of consciousness, and present empirical examples of sequence learning studies in which these different procedures were applied to differentiate between implicit and explicit knowledge acquisition. We also show how the use of a sensitive behavioral method, the process dissociation procedure, confers a distinctive advantage in brain-imaging studies when aiming to delineate the neural correlates of conscious and unconscious processes in sequence learning.


Changing epidemiology of hepatitis A in the Bologna metropolitan area, northern Italy: importance of counselling and prophylactic measures for the male homo/bisexual population.
During a 6-year observational study, 122 cases of hepatitis A virus (HAV) infection were detected in Bologna, Italy, with a c. 300% increase in cases between 1999 and 2004. There were 104 cases (85.2%) in male adults, of whom nearly 70% had unprotected sexual contact as the probable risk-factor. There were increasing numbers of cases in immigrants between 1999 and 2004 (p 0.036), and concurrent cases of infection with human immunodeficiency virus, hepatitis B and C viruses and syphilis were also noted in adult males (p 0.0032). There is a need to re-emphasise targeted educational programmes and anti-HAV vaccination for at-risk subjects.


Preoperative small airway dysfunction is associated with skeletal muscle loss in early-stage non-small cell lung cancer.
Postoperative skeletal muscle loss (SM loss) was reported to be associated with a poor prognosis in early-stage non-small cell lung cancer (NSCLC). Small airway dysfunction (SAD) is a common but neglected respiratory abnormality. Little information is known about the association between preoperative SAD and postoperative SM loss in early-stage NSCLC. Therefore, this study aimed to investigate the correlation between preoperative SAD and SM loss after surgery in early-stage NSCLC patients. There were 348 NSCLC patients with stages I-IIIA in this study from January 2017 to December 2020. All CT images were contrast-enhanced scans, and the skeletal muscle index (SMI) was measured using CT images. A 10.0% decrease in SMI over 12 months was determined as the cut-off value to define excessive SM loss. Logistic regression analyses were used to examine the relationship between SAD and SM loss. This study included 348 subjects who underwent pulmonary operation (159 males and 189 females; mean age: 57.5 ± 8.8 years). 152 (43.7%) patients were identified as having SAD before surgery, and 179 patients (51.4%) were identified as having SM loss after 1 year. Moreover, a higher incidence of SAD was found in the SM loss group compared with that in the non-SM loss group (52.0% vs. 34.9%, p = 0.001). The patients with SAD were older, had larger tumor size, and had lower albumin levels. Furthermore, there were significant correlations between the lung function parameters manifesting SAD and the percentage change in SMI (for the forced expiratory flow when 75% of forced vital capacity has been exhaled (FEF75%), Pearson r=-0.107, p = 0.046; for FEF50%, r = -0.142, p = 0.008; and for FEF25-75%, r=-0.124, p = 0.021; respectively). However, no significant correlations were found between SMI and the lung function parameters reflecting proximal airway obstruction (p > 0.05). Logistic regression analysis revealed that preoperative SAD (HR, 2.465; 95% CI, 1.256-4.838; p = 0.009) was independent risk factor for postoperative SM loss in early-stage NSCLC. In addition, multivariable analysis revealed that SAD (HR, 1.816; 95% CI, 1.025-3.216, P = 0.041) were associated with postoperative complications. Preoperative SAD is significantly associated with postoperative complications and SM loss in early NSCLC patients. Our results suggest that preoperative assessment of SAD may be useful for risk stratification of surgical candidates with potential for targeted interventions.


On chip electrochemical detection of sarcoma protein kinase and HIV-1 reverse transcriptase.
In this study, we report a new multiplexed microchip platform exploiting a peptide-modified gold surface and a labeled electrochemical approach. The significance of the presented methodology lies in its ability to test related analytes, such as protein kinases and human immunodeficiency virus (HIV) proteins, that operate under separate mechanisms using a single device without interference. The technology is based on an electrochemical dual sensing mode that can be tuned towards monitoring separately two biochemical events, a biochemical reaction and a direct analyte-receptor binding. The first recognition process is illustrated by a sarcoma-related (Src) protein kinase which catalyzes phosphorylation transfer of a ferrocenoyl-phosphoryl group, from the ferrocene-labeled adenosine triphosphate (Fc-ATP) co-substrate, to the surface-bound target peptide and induces a current response. On the other hand, HIV-1 reverse transcriptase (RT) protein binding to the surface-immobilized ferrocene-labeled target peptide is characterized by a modulation in the current intensity and peak potential. This proof-of-principle study is based on two different biosensing components and serves as a new platform for monitoring multiple analytes of interest. This allowed detection limits of 0.1 μg mL(-1) and 50 pg mL(-1) for Src kinase and HIV-1 RT, respectively. The miniaturization of the electrochemical protein assay will have an impact in disease detection and treatment.


Trimeric, coiled-coil extension on peptide fusion inhibitor of HIV-1 influences selection of resistance pathways.
Peptides corresponding to N- and C-terminal heptad repeat regions (HR1 and HR2, respectively) of viral fusion proteins can block infection of viruses in a dominant negative manner by interfering with refolding of the viral HR1 and HR2 to form a six-helix bundle (6HB) that drives fusion between viral and host cell membranes. The 6HB of the HIV gp41 (endogenous bundle) consists of an HR1 coiled-coil trimer with grooves lined by antiparallel HR2 helices. HR1 peptides form coiled-coil oligomers that may bind to gp41 HR2 as trimers to form a heterologous 6HB (inhibitor bundle) or to gp41 HR1 as monomers or dimers to form a heterologous coiled coil. To gain insights into mechanisms of Env entry and inhibition by HR1 peptides, we compared resistance to a peptide corresponding to 36 residues in gp41 HR1 (N36) and the same peptide with a coiled-coil trimerization domain fused to its N terminus (IZN36) that stabilizes the trimer and increases inhibitor potency (Eckert, D. M., and Kim, P. S. (2001) Proc. Nat. Acad. Sci. U.S.A. 98, 11187-11192). Whereas N36 selected two genetic pathways with equal probability, each defined by an early mutation in either HR1 or HR2, IZN36 preferentially selected the HR1 pathway. Both pathways conferred cross-resistance to both peptides. Each HR mutation enhanced the thermostability of the endogenous 6HB, potentially allowing the virus to simultaneously escape inhibitors targeting either gp41 HR1 or HR2. These findings inform inhibitor design and identify regions of plasticity in the highly conserved gp41 that modulate virus entry and escape from HR1 peptide inhibitors.


Anesthesia for ventricular assist device placement: experience from a single center.
Circulatory support with ventricular assist systems has become a treatment alternative for patients with end-stage heart failure owing to the donor shortage. In this report, we have presented our institution's clinical experience in the anesthetic management of ventricular assist device (VAD) implantation. Between April 2007 and August 2012, VAD implantation was performed in 84 adult patients with end-stage heart failure. The group included 75 male and 9 female patients of overall mean age, 47.6 ± 13.4 years. Our retrospective review analyzed elements of perioperative anesthetic care, including preoperative characteristics, general anesthetic care, and blood product usage. The indications for VAD implantation were dilated (n = 59; 70%) or ischemic cardiomyopathy (n = 25; 30%). An intra-aortic balloon pump had been placed in 16 patients. We monitored invasive arterial and central venous pressures as well as intraoperative transesophageal echocardiography. Etomidate was used as the induction agent in 79 of 84 patients (average dose, 18.75 ± 1.40 mg). Intraoperative fentanyl dose was 939.69 ± 212.44 μg. Anesthesia was maintained with sevoflurane (n = 55) or desflurane (n = 29). Dopamine, dobutamine, epinephrine, norepinephrine, and levosimendan were used in 74, 79, 60, 14, and 32 patients, respectively. Inhaled nitric oxide was administered to 38 subjects (45%). The amounts of perioperative blood, fresh frozen plasma, and thrombocyte suspension transfusions were 3.96 ± 2.78, 1.91 ± 1.21, 1.80 ± 2.48 u, respectively. On average, patients were extubated 13 hours after arrival in the intensive care unit and discharged therefrom on day 8. Thirty-one patients were successfully bridged to heart transplantation. While 27 patients (32%) died during the follow-up period, 26 are still living on VAD support. Among patients undergoing VAD implantation, the anesthesiologist should become familiar with the device and consider the severity of cardiac and other end-organ dysfunction.


Factors influencing adherence to the new intermittent preventive treatment of malaria in pregnancy policy in Keta District of the Volta region, Ghana.
About 25% of pregnant women in malaria-endemic areas are infected with malaria and this accounts for about 15% of maternal deaths globally. Intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is one of the main strategies for prevention of malaria in pregnancy. A new recommendation was made by the World Health Organization (WHO) that at least three doses of IPTp-SP should be administered before delivery. This study sought to determine the factors influencing adherence to the new IPTp-SP policy in Keta District, Volta region, Ghana. A cross-sectional quantitative study among 375 nursing mothers at four selected health facilities in Keta district, Ghana was conducted using a structured questionnaire to interview participants. Sampling proportionate to the size of facility was used to determine the number of nursing mothers from each facility based on the caseload. For each facility systematic random sampling was used to select eligible nursing mothers. Data was analyzed using STATA 15. Chi-square was used to test bivariate association between categorical variables and adherence. Logistic regression analysis was used to examine sociodemographic, individual and institutional factors influencing adherence to IPTp-SP. About 82.1% of participants adhered to the WHO policy recommendations of at least three doses of IPTp-SP. However, only 17.1% received Ghana's five dose coverage recommendation. The proportion of IPTp-SP coverage for IPTp1 was 98.9%; IPTp2 95.5%; IPTp3 80.8%; IPTp4 39.5%; IPTp5 17.1%. Adherence to IPTp-SP was satisfactory according to WHO's policy recommendation, however, majority of the participants had less than the five doses recommended in Ghana. Number of Antenatal Care (ANC) visits and knowledge of malaria were the main determinants of adherence to IPTp-SP.


Postinflammatory increase of absorption from peritoneal cavity into lymph nodes: particulate and oily inocula.
One week after intraperitoneal injection of rats and mice with a chemical irritant, the abdominal cavity was in the healing phase of a sterile peritonitis. At this time, mineral oil or a particulate dye or metal injected intraperitoneally was absorbed into lymph nodes in much larger amounts than normal. Absorption of oil caused fourfold enlargement of nodes, distention of afferent lymphatics, and sometimes widespread oil embolization of lungs. Absorption was increased when the chemical irritant had bathed the entire peritoneum but not when it was limited to the lower abdominal cavity. The chemical peritonitis caused shrinkage, agglutination, fixation, and fibrosis of the greater omentum which thereby lost its ability to sequester particles. In the absence of omental scavenging, dye, metal, or oil accumulated under the diaphragm and penetrated the diaphragmatic lymphatics. In addition, enhanced absorption by proliferated subdiaphragmatic lymphatics may have been involved. Prior induction of a chemical peritonitis augments absorption into the lymphatics of certain aqueous and cellular as well as particulate and oily inocula, so it is likely to find many applications in experimental pathology.


[Effect of Manasan on fecal pH, fecal microflora and acid-base homeostasis in young infants].
Manasan is an adapted formula for infants on the basis of cow's milk simulating the mode of action of human milk on faeces-pH and faeces microflora. In two temporally separated tests the effect of Manasan-feeding on faeces-pH, faeces flora, and acid-base-homeostasis was controlled and compared with the effect of human milk and Ki-Na-formula. With Manasan fed up from birth or following breast-feeding faeces-pH was to be found in an acid range, clearly. With Ki-Na the faeces-pH was situated in the neutral range. With Manasan the bacteria flora revealed a noteworthy decrease in the number of Bacteroides germs achieving a non-putrefactive milieu. Concerning the acid-base-homeostasis as with human milk so with Manasan late metabolic acidosis were to meet rarely. The experiments revealed that in important parameters, particularly with microecological signs, Manasan is comparable with human milk.


Continuous intake of quercetin-rich onion powder may improve emotion but not regional cerebral blood flow in subjects with cognitive impairment.
Depression in later life is associated with dementia. Changes in motivated behavior are an important mechanism contributing to dysfunctional cognitive control in depression. Although continuous intake of quercetin-rich onion suppresses cognitive decline in aged people by improving their emotional condition, the effect of quercetin-rich onion on emotional condition in people living with cognitive impairment remains unclear. In this randomized, double-blind, placebo-controlled study of subjects with cognitive impairment, we found that subjects wrote more adjectives and adverbs per sentence on the Mini-Mental State Examination after intake of quercetin-rich onion powder than before intake, although regional cerebral blood flow on n-isopropyl-4-[123]iodoamphetamine hydrochloride single-photon emission computed tomography was not changed. In the EPM, mice that had received a quercetin-supplemented chow diet made a significantly increased number of exploratory head dips from the open arms of the maze. Moreover, the 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl decay rate, reflecting redox activity, was increased in mice fed a quercetin-added diet. These results indicate that quercetin-rich onion may affect motivated behavior in subjects with cognitive impairment, for whom quercetin intake may preserve redox homeostasis in the brain.


Perioperative noninvasive ventilation in obese patients: a qualitative review and meta-analysis.
Perioperative noninvasive ventilation (NIV) has been proposed to reduce postoperative morbidity and improve perioperative outcomes in patients undergoing general anesthesia. Whether it is advantageous to apply NIV just before and after general anesthesia in obese patients has not been yet established. To perform a qualitative review and meta-analysis to assess the effectiveness and tolerability of perioperative NIV in obese patients. All studies in English language performed in clinical setting that compared the application of NIV with standard care just before and after induction of general anesthesia in obese adults (body mass index [BMI]≥35 kg/m(2)) were included. Data on oxygenation, respiratory function, complications, and outcomes were extracted. Twenty-nine articles were selected and used in the qualitative review. Eleven studies including 768 patients were used for subsequent meta-analyses. Compared with standard preoxygenation, NIV was associated with a significant improvement in oxygenation (P<.0001) before tracheal intubation. Benefits in oxygenation (P<.0001), clearance of carbon dioxide (P<.0001), and pulmonary function testing (P<.0001) after general anesthesia were observed with NIV compared with standard care. Postoperatively, NIV was associated with a decreased risk of respiratory complications (relative risk [RR] = .33; 95% confidence interval [CI] .16-.66; P = .002), but not of reintubation after tracheal extubation (RR = .41; 95% CI .09-1.82]; P = .3657) and unplanned intensive care unit admission (RR = .43; 95% CI .16-1.15; P = .0937). NIV-related complications in obese patients were mainly due to intolerance and ranged from 7% to 28% of cases. NIV-related anastomotic leakage and adverse events were not reported. Results from this review and meta-analysis suggest that NIV is well tolerated and effective in improving perioperative care in obese patients. The application of NIV before and after general anesthesia should be considered and promoted in relevant cases.


A scoping review of the use of e-learning and e-consultation for healthcare workers in low- and middle-income countries and their potential complementarity.
Although the provision of e-learning (EL) training for healthcare workers (HCWs) and provider-to-HCW e-consultation (EC) is considered useful for health outcomes, research on their joint use is limited. This scoping review aimed to create an overview of what is currently known in the literature about the use and implementation of EC and EL by HCWs in LMICs and to answer the question of whether there is evidence of complementarity. Scientific databases were searched and peer-reviewed papers were reviewed systematically according to predefined inclusion/exclusion criteria. Data were extracted including the study focus (EC/EL), year of publication, geographical location, target population, target disease(s) under study, type(s) of study outcomes, and article type. A total of 3051 articles were retrieved and screened for eligibility, of which 96 were kept for analysis. Of these, only 3 addressed both EL and EC; 54 studies addressed EL; and 39 addressed EC. Most studies looked at gain in knowledge/skills usability, efficiency, competence, and satisfaction of HCW, or barriers/challenges to implementation. Descriptive studies focused on the application of EL or EC for targeting specific health conditions. Factors contributing to the success of EC or EL networks were institutional anchoring, multiple partnership, and capacity building of local experts. Our review found an important gap in the literature in relation to the complementary role of EL and EC for HCWs in LMICs evidenced by outcome measures. There is an important role for national and international academic institutions, learned medical societies, and networks to support regional experts in providing EL and EC for added value that will help the clinical performance of HCWs and improve health outcomes.


Cardiac MRI in muscular dystrophy: an overview and future directions.
Cardiac complications are a common feature of many muscular dystrophies. Although many modalities (eg, ultrasound) provide exceptional efficacy for early diagnosis, repeated monitoring, and therapeutic management, MRI has become the gold standard for anatomic and functional characterization. An increasing number of studies, especially in the dystrophinopathies, use strain imaging to evaluate function. This article summarizes these studies and attempts to integrate an understanding of other relevant cardiac features (eg, fibrosis) into interpreting this work. Finally, a general roadmap forward is provided as these tools are increasingly used for treatment assessment and tactical patient management in the future.


Absorption Spectroscopy, Emissive Properties, and Ultrafast Intersystem Crossing Processes in Transition Metal Complexes: TD-DFT and Spin-Orbit Coupling.
Absorption spectroscopy, emissive properties, and ultrafast intersystem crossing processes in transition metal complexes are discussed in the light of recent developments in time-dependent density functional theory (TD-DFT), spin-orbit coupling (SOC) effects, and non-adiabatic excited states dynamics. Methodological highlights focus on spin-orbit and vibronic couplings and on the recent strategies available for simulating ultra-fast intersystem crossings (ISC).The role of SOC in the absorption spectroscopy of third-row transition metal complexes is illustrated by two cases studies, namely Ir(III) phenyl pyridine and Re(I) carbonyl bipyridine complexes.The problem of luminescence decay in third-row transition metal complexes handled by TD-DFT linear and quadratic response theories including SOC is exemplified by three studies: (1) the phosphorescence of Ir(III) complexes from the lowest triplet state; (2) the emissive properties of square planar Pt(II) complexes with bidentate and terdentate ligands characterized by low-lying metal-to-ligand-charge-transfer (MLCT) and metal-centered (MC) states; and (3) the ultra-fast luminescence decay of Re(I) carbonyl bipyridine halides via low-lying singlet and triplet charge transfer states delocalized over the bipyridine and the halide ligands.Ultrafast ISC occurring in spin crossover [Fe (bpy)3]2+, in [Ru (bpy)3]2+, and [Re (Br)(CO)3(bpy] complexes are deciphered thanks to recent developments based on various approaches, namely non-radiative rate theory within the Condon approximation, non-adiabatic surface hopping molecular dynamics, and quantum wave packet dynamics propagation.


Treatment of adenocarcinoma of the cardia with synchronous chemotherapy and radiotherapy.
Twenty-nine evaluable patients with adenocarcinoma of the cardia were treated with synchronously administered chemotherapy (two cycles of 5-fluouracil and cisplatin and 30-36 Gy of radiation to determine whether these tumours are responsive to such treatment. Complete regression of tumour was observed endoscopically in 19 patients, and partial regression in four. Fourteen patients had their tumours resected and in six no microscopic tumour was found in the specimen. Nine patients received additional radiotherapy to a total dose of 54-60 Gy instead of surgery. Tumour response was associated with rapid reversal of dysphagia. Only one patient required subsequent intervention for relief of dysphagia due to fibrous stricture. Enhanced survival was associated with a complete endoscopic response to initial chemotherapy and radiotherapy, and a tumour of less than 5 cm in length. The median survival of responding patients was 15 months. Synchronous chemotherapy and radiotherapy was of major palliative benefit in this series and merits further evaluation.


Clear cell chondrosarcoma arising from the sternum: a rare tumor in an uncommon location.
A 52-year-old woman presented with bulging of the anterior chest wall. The computed tomographic scan revealed an expansive localized mass based on the sternal manubrium. The patient was successfully treated with en bloc radical resection and reconstruction with clear resection margin. Histopathologic examination of the surgical specimen confirmed the diagnosis of clear cell chondrosarcoma. After the surgery, the patient has been free of disease for 43 months after surgery without other treatment. Our search and review of the literature did not reveal any published cases of clear cell chondrosarcoma arising from the sternum; therefore, we have presented a summary of this novel case with a review of the relevant literature.


Time dependent degradation of vitreous gel under enzymatic reaction: Polymeric network role in fluid properties.
The viscoelastic behavior of vitreous gel is due to the presence of biopolymers in its structure. Fluid properties of the vitreous is mainly the result of interactions between the characteristics of collagen type II and Hyaluronic Acid networks. Having a better understanding of the structure of each component and their changes during aging and various diseases such as diabetes can lead to better monitoring and treatment options. We study the effects of collagenase type II on 44 samples of porcine vitreous using an in situ rheological experiment in comparison with 18 eyes in a control group injected with Phosphate Buffered Saline Solution. We analyze the behavior of each component over time in both groups. We focus on the changes of viscosity and elasticity of the collagen network within the vitreous. The results of the analysis in this study show that the changes in the fluid properties of the vitreous after collagenase injection is driven by the structural alterations of the collagen network. Creep compliance values of the collagen network are significantly higher in the first group compared to the control group one hour and twenty-four hours after the injection. In contrast, creep compliance of the HA network shows no statistically significant change one hour after the injection in both groups. The results of the reported analysis of individual components in this study support the previous findings on the alterations within the vitreous structure in its entirety.


Validation of a point-of-care handheld blood total calcium analyzer in postpartum dairy cows.
Our objective was to validate a point-of-care handheld blood total calcium analyzer (Ca meter, CM; TD-5220 Vet Ca2+, TaiDoc, New Taipei, Taiwan) to estimate circulating Ca concentrations in postpartum dairy cows. Whole blood was collected from 251 multiparous cows between 1 and 4 d in milk from 2 commercial dairy herds in Ontario, Canada. Blood total calcium concentration (tCa) was analyzed in whole blood, fresh plasma, and thawed plasma, and compared with tCa results from thawed serum analyzed in a diagnostic laboratory (using a Cobas Calcium Gen 2 kit, Roche Diagnostics, Indianapolis, IN) as the reference test (RT). Lin's concordance correlation coefficient (βrho;) and Bland-Altman (B-A) plots were assessed to evaluate the agreement between the RT and CM results in each type of sample. Receiver operating characteristic curve analyses were used to describe the accuracy of each test against the categorized RT results (at a cut-point of ≤2.14 mmol/L). Samples where the meter gave a nonquantitative result ("high" or "low"; thawed plasma: 3/247; fresh plasma: 6/100; and whole blood: 20/98) were not included in the βrho; and B-A analyses. Lin's correlation coefficients demonstrated poor agreement between tests (thawed plasma: βrho; = 0.16; fresh plasma: βrho; = 0.21; and whole blood: βrho; = 0.23). Fresh plasma (using a cut-point of 2.55 mmol/L as measured on the CM) had the greatest diagnostic sensitivity (72%), specificity (86%), and accuracy (77%) for determining subclinical hypocalcemia, but that would still misclassify 23% of samples. In addition to substantial variability, the B-A plots revealed bias with changing concentrations of calcium. Because of low sensitivity on whole blood (58%) or thawed plasma (56%), measurement with the CM is not recommended on these types of samples. This rapid and low-cost meter was not sufficiently accurate to quantify blood Ca concentration, but when used with fresh plasma it might be useful as a screening tool for subclinical hypocalcemia.


Retracted: A Prediction Model Analysis of Behavior Recognition Based on Genetic Algorithm and Neural Network.
[This retracts the article DOI: 10.1155/2022/3552908.].


Management of serous cystadenoma of the pancreas.
Serous cystadenoma of the pancreas is a diagnosis being entertained with increasing frequency. The histopathologic findings, diagnostic strategy, differential diagnosis, and treatment strategy of these generally benign but sometimes symptomatic lesions are discussed. Based on the available case series, surgical resection should be considered in good-risk patients with symptomatic tumors, with tumors at least 4 cm in maximum diameter, or in whom a more worrisome diagnosis cannot be excluded.


Algorithms for Warping of 2-D PAGE Maps.
Software-based image analysis of 2-D PAGE maps is an important step for the investigation of proteome. Warping algorithms, which are employed to register spots among gels, are able to overcome the difficulties due to the low reproducibility of this analytical technique. Over the years, the research of new matching and warping mathematical methods has allowed the development of several routine applications of easy-to-use software. This chapter describes common and basic spatial transformations used for the alignment of protein spots present in different gel maps; some recently new approaches are also presented.


Assessment of the incidence of fragmented QRS in electrocardiography in patients with systemic sclerosis and systemic lupus erythematosus.
In systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) cardiac involvement is very common, and it might be asymptomatic. We aimed to assess the presence of fragmented QRS (fQRS) - possible indicator of a scar, diffuse damage or conduction system disturbances in those patients. We examined 74 patients with SSc, 77 with SLE and 40 healthy controls. The incidence of fQRS in ECG was examined according to criteria by Das et al. Disease severity was estimated by Rodnan and SLICCC/ACRDI scores in SSc and SLE respectively. Patients with SSc were slightly older than those with SLE (53 ± 14 vs 46 ± 14 yrs), women constituted 91% and 88% of studied groups (p = 0.80). The duration of disease in both groups was similar (p = 0.59). Median of Rodnan and SLICCC/ACR-DI scores were 5 and 4 points, respectively. Left ventricle ejection fraction in both groups was similar (65.5 vs 65.1%, p = 0.51), hypertension incidence was lower in SSc (24 vs 48%, p = 0.004), patients with SLE presented prolonged corrected QT interval (432 vs 424 ms, p = 0.03). Of note, fQRS were observed in 34 (46%) SSc and 29 (38%) SLE patients, p = 0.33. Notched S waves were significantly more frequent in SSc (in 26% vs 10%, p = 0.02). fQRS occurred in 3 (7.5%) of healthy subjects only. The incidence of fQRS is similar in SSc and SLE, but is much more common than in healthy subjects. It is possible that fQRS may be considered an additional marker of heart involvement in these rare diseases.


A method for purification and characterisation of Mycobacterium avium subsp. paratuberculosis from the intestinal mucosa of sheep with Johne's disease.
Mycobacterium avium subsp. paratuberculosis, the cause of Johne's disease in ruminants, cannot be cultured in large quantities from affected sheep in Australia. A method is described for the purification of the organism from the intestinal mucosa of sheep with multibacillary Johne's disease in order to undertake restriction fragment length polymorphism (RFLP) analysis for epidemiological purposes. Using sucrose and potassium chloride as separation media for differential and density gradient centrifugation, yields of approximately 90 mg dry weight M. avium subsp. paratuberculosis per 5 g intestinal mucosa were obtained. The preparations of purified M. avium subsp. paratuberculosis were visually free of non-acid fast bacteria and contained 10(2)-10(3) aerobic/ facultatively anaerobic organisms per gram wet weight. DNA extracted from purified M. avium subsp. paratuberculosis was examined by hybridisation with an IS900 probe after digestion with BstEII and RFLP patterns distinct from isolates from cattle were obtained. The RFLP pattern of purified M. avium subsp. paratuberculosis from five sheep matched that obtained previously from organisms cultured from sheep in studies in New Zealand, indicating that the purification and RFLP method is robust.


CardioVision: A fully automated deep learning package for medical image segmentation and reconstruction generating digital twins for patients with aortic stenosis.
Aortic stenosis (AS) is the most prevalent heart valve disease in western countries that poses a significant public health challenge due to the lack of a medical treatment to prevent valve calcification. Given the aging population demographic, the prevalence of AS is projected to rise, resulting in a progressively significant healthcare and economic burden. While surgical aortic valve replacement (SAVR) has been the gold standard approach, the less invasive transcatheter aortic valve replacement (TAVR) is poised to become the dominant method for high- and medium-risk interventions. Computational simulations using patient-specific models, have opened new research avenues for optimizing emerging devices and predicting clinical outcomes. The traditional techniques of generating digital replicas of patients' aortic root, native valve, and calcification are time-consuming and labor-intensive processes requiring specialized tools and expertise in anatomy. Alternatively, deep learning models, such as the U-Net architecture, have emerged as reliable and fully automated methods for medical image segmentation. Two-dimensional U-Nets have been shown to produce comparable or more accurate results than trained clinicians' manual segmentation while significantly reducing computational costs. In this study, we have developed a fully automatic AI tool capable of reconstructing the digital twin geometry and analyzing the calcification distribution on the aortic valve. The developed automatic segmentation package enables the modeling of patient-specific anatomies, which can then be used to simulate virtual interventional procedures, optimize emerging prosthetic devices, and predict clinical outcomes.


Mitochondrial DNA methylation drift and postoperative delirium in mice.
Mitochondrial dysfunction is linked to the etiopathogenesis of postoperative delirium (POD), which severely affects the prognosis of elderly patients undergoing surgery. The methylation of mitochondrial DNA (mtDNA), a new and incompletely described phenomenon that regulates the structure and function of mitochondria, is associated with ageing. However, the relationship between mtDNA methylation and POD has not been established. To explore the potential roles of mitochondrial epigenetic regulation in POD. A randomised animal study. Eighty-eight 6-month-old and one hundred seventy-six 18-month-old male C57BL/6N mice. POD was induced by abdominal surgery under 1.4% isoflurane for 2 h. Behavioural tests were performed at 24 h before surgery and at 6, 9 and 24 h after surgery. 5-methylcytosine (5-mC) at five CpG sites of the displacement loop (D-loop) and at 60 CpG sites of coding gene loci in the mitochondrial genome after surgery of the hippocampus, prefrontal cortex, amygdala and anterior cingulate cortex in 6 and 18-month-old mice were detected using bisulfite pyrosequencing. Mitochondrial structure, mitochondrial gene expression and mtDNA copy number were also examined using Electron microscopy and real time PCR to find the association with mtDNA methylation. The mtDNA methylation drift manifested as a decrease in the methylation levels at the D-loop and an increase or decrease in the methylation levels at several coding gene loci, ultimately resulting in reduced mtDNA copy numbers, altered mitochondrial gene expression and damaged mitochondrial structures in the hippocampus and prefrontal cortex after surgery. The activation of Silent information regulator-1 (SIRT1) ameliorated anaesthesia-induced and surgery-induced mitochondrial dysfunction and delirium-like behaviours by regulating mtDNA methyltransferase-mediated mtDNA methylation. These data support the existence of epigenetic mtDNA regulation in POD; however, further studies are required to explore the specific mechanisms. No 20181204 Drum tower hospital.


A kinetic analysis of electron transport across chromaffin vesicle membranes.
Some types of secretory vesicles, such as the chromaffin vesicles of the adrenal medulla, have cytochrome b561 which is believed to mediate the transfer of electrons across the vesicle membrane. To characterize the kinetics of this process, we have examined the rate of electron transfer from ascorbate trapped within chromaffin vesicle ghosts to external ferricyanide. The rate of ferricyanide reduction saturates at high ferricyanide concentrations. The reciprocal of the rate is linearly related to the reciprocal of the ferricyanide concentration. The internal ascorbate concentration affects the y intercept of this double-reciprocal plot but not the slope. These observations and theoretical considerations indicate that the slope is associated with a rate constant k1 for the oxidation of cytochrome b561 by ferricyanide. The intercept is associated with a rate constant k0 for the reduction of cytochrome b561 by internal ascorbate. From k0 and standard reduction potentials, the rate constant k-0 for the reduction of internal semidehydroascorbate by cytochrome b561 can be calculated. Under conditions prevailing in vivo, this rate of semidehydroascorbate reduction appears to be much faster than the expected rate of semidehydroascorbate disproportionation. This supports the hypothesis that cytochrome b561 functions in vivo to reduce intravesicular semidehydroascorbate thereby maintaining intravesicular ascorbic acid.


Cortical sensorimotor alterations in Unverricht-Lundborg disease patients without generalized seizures.
We investigated cortical functions of two Unverricht-Lundborg disease (ULD) patients suffering from myoclonic jerks, but no generalized tonic-clonic seizures. Somatosensory cortical responses were recorded to median nerve stimuli and coherence was calculated between cortical and muscle signals during isometric contraction of hand muscle. In contrast to ULD patients with generalized tonic-clonic seizures, responses of the primary somatosensory (SI) cortex were only slightly enhanced in the left and normal in the right hemisphere, and no early responses were observed in the ipsilateral SI. Cortex-muscle coherence was remarkably enhanced. We conclude that in ULD patients without generalized tonic-clonic seizures, both the excitability of the SI and transcallosal conduction are relatively normal, probably decreasing susceptibility to generalized seizures. Disturbed cortical control of muscle contraction indicates selective alteration of the motor cortex activation.


Delivery of Radioiodine Ablation in a Patient with End-Stage Renal Disease.
This case presents a pragmatic approach to the management of a radioiodine remnant ablation patient on hemodialysis which required no pretherapeutic dosimetric measurements. Pretreatment radiation dose modeling was performed using literature values for radioiodine hemodialysis extraction efficacies to determine a safe treatment regimen including adjustment of the administered activity and hemodialysis frequency. The pretreatment modeling was subsequently verified using external and blood radiation monitoring during treatment.


High frequency characterization of Si 3 N 4 dielectrics for artificial magnetoelectric devices.
Charge mediated magnetoelectric coupling mechanism in artificial multiferroics originates from interfacial charge modulation or ionic movement at a magnetic/dielectric interface. Despite the existence of several dielectric/ferroelectric systems that can be used in charge mediated artificial multiferroic systems, producing suitable systems with fast time responses still remains a challenge. Here we characterize the frequency response of stoichiometric and non-stoichiometric (low strain) Si 3 N 4 thin film membranes, which can potentially be used as the dielectric layer in magnetoelectric devices, to determine the impact of depletion layers, charge traps and defect mobility on the high frequency (up to 100 MHz) interfacial charge modulation via screening. We find that the dielectric/magnetoelectric properties are largely dominated by extrinsic doping due to point defects. In particular, we find that non-stoichiometric Si 3 N 4 has a dielectric behaviour that is dominated by charge traps and/or mobile ions. However, stoichiometric Si 3 N 4 membranes show a reversible response to the applied bias electric field consistent with a doped semiconductor behaviour; at high frequencies, the intrinsic dielectric behaviour is reached, indicating that it may be suitable for high frequency magnetoelectric device applications. Our results show that minimising the impact of defects on the dielectric properties of magnetoelectric heterostructures is an important prerequisite for obtaining a high frequency magnetoelectric response. The online version contains supplementary material available at 10.1007/s10853-022-07832-2.


Extraction of low-dimensional features for single-channel common lung sound classification.
In this study, feature extraction methods used in the classification of single-channel lung sounds obtained by automatic identification of respiratory cycles were examined in detail in order to extract distinctive features at the lowest size. In this way, it will be possible to design a system for the detection of lung diseases, completely autonomously. In the study, automatic separation and classification of 400 respiratory cycles were performed from the single-channel common lung sounds obtained from 94 people. Leave one out cross validation (LOOCV) was used for the calibration and validation of the classification model. The Mel frequency cepstrum coefficients (MFCC), time domain features, frequency domain features, and linear predictive coding (LPC) were used for classification. The performance of the features was tested using linear discriminant analysis (LDA), k-nearest neighbors (k-NN), support vector machines (SVM), and naive Bayes (NB) classification algorithms. The success of combinations of features was explored and enhanced using the sequential forward selection (SFS). As a result, the best accuracy (90.14% in the training set and 90.63% in the test set) was acquired using the k-NN for the triple combination, which included the standard deviation of LPC and the standard deviation and the mean of MFCC.


Outcomes of reoperative aortic valve replacement via right mini-thoracotomy versus median sternotomy.
The study aim was to determine the safety and efficacy of a minimally invasive right mini-thoracotomy for aortic valve replacement (AVR) in patients who had undergone previous median sternotomy. Between January 2005 and December 2011, a total of 3,603 consecutive cases was retrospectively reviewed to identify patients with previous median sternotomy who subsequently underwent AVR. The outcomes of patients having minimally invasive surgery were compared with those in whom a median sternotomy approach had been employed. Among 77 patients identified, 36 (47%) underwent a minimally invasive approach, and 41 (53%) had a median sternotomy. The mean age of the minimally invasive group (33 males, three females) was 75.3 +/- 9.0 years, and that of the median sternotomy group (33 males, eight females) was 68.2 +/- 13.6 years (p = 0.009). The minimally invasive group had more prior sternotomy for coronary artery bypass graft surgery (86% versus 59%, p = 0.007), and fewer for prior valve surgery (33% versus 59%, p = 0.02). In-hospital mortality was zero for the minimally invasive cohort versus four (10%) in the median sternotomy group (p = 0.08); composite postoperative complications occurred in six (17%) versus 19 (46%) (p = 0.005) of these two groups, respectively. The median intensive care unit and total hospital length of stay were 48 h [interquartile range (IQR) 41-97] versus 69 h [IQR 45-174] (p = 0.03), and seven days [IQR 5-10] versus 9 days [IQR 7-15] (p = 0.03) for the minimally invasive and median sternotomy group, respectively. Minimally invasive AVR via a right mini-thoracotomy in patients with previous cardiac surgery can be performed safely, and is associated with shorter intensive care unit and total hospital stays, a lower morbidity, and a trend towards lower mortality.


TES-1/Tes and ZYX-1/Zyxin protect junctional actin networks under tension during epidermal morphogenesis in the C. elegans embryo.
LIM-domain-containing repeat (LCR) proteins are recruited to strained actin filaments within stress fibers in cultured cells,1,2,3 but their roles at cell-cell junctions in living organisms have not been extensively studied. Here, we show that the Caenorhabditis elegans LCR proteins TES-1/Tes and ZYX-1/Zyxin are recruited to apical junctions during embryonic elongation when junctions are under tension. In genetic backgrounds in which embryonic elongation fails, junctional recruitment is severely compromised. The two proteins display complementary patterns of expression: TES-1 is expressed in lateral (seam) epidermal cells, whereas ZYX-1 is expressed in dorsal and ventral epidermal cells. tes-1 and zyx-1 mutant embryos display junctional F-actin defects. The loss of either protein strongly enhances morphogenetic defects in hypomorphic mutant backgrounds for cadherin/catenin complex (CCC) components. The LCR regions of TES-1 and ZYX-1 are recruited to stress fiber strain sites (SFSSs) in cultured vertebrate cells. Together, these data establish TES-1 and ZYX-1 as components of a multicellular, tension-sensitive system that stabilizes the junctional actin cytoskeleton during embryonic morphogenesis.


Effectiveness of vitamin D for irritable bowel syndrome: A protocol for a systematic review of randomized controlled trial.
Irritable bowel syndrome (IBS) is a prevalent and debilitating condition for patients who experience this disorder. Clinical researches indicate that vitamin D (VD) can help relief the symptoms of IBS. However, no systematic review has addressed this issue yet. Thus, this systematic review aims to investigate the effectiveness and safety of VD for patients with IBS. We will retrieve the following databases for randomized controlled trials to assess the effectiveness and safety of VD for patients with IBS: Cochrane Library, EMBASE, MEDICINE, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. Each database will be retrieved from its inception to January 31, 2019. Two researchers will independently selection studies, extract data and assess methodological quality. RevMan 5.3 software will be used to pool the data, and carry out the meta-analysis if it is possible. This systematic review will evaluate the effectiveness and safety of VD for patients with IBS. The primary outcomes include stool frequency and abdominal pain. The secondary outcomes consist of stool status, quality of life, and adverse effects. The findings of this systematic review may provide the existing evidence on the effectiveness and safety of VD for patients with IBS. This systematic review will not require ethical approval, because all data will be extracted from the published literature. The findings of this study will be disseminated at peer-reviewed journals.PROSPERO registration number: PROSPERO CRD42019122641.


A histological study of the use of agar as a delivery vehicle for alcohol or iron to rats.
The supply of ethanol and other substances to the rat has necessitated the development of quite complex dietary preparation and feeding techniques. This study reports the use of ethanol/water solutions in conjunction with normal rat chow diet to provide up to 30 g/kg/day ethanol to study animals. By additionally supplying agar gels containing ethanol, voluntary intake of ethanol was raised to a possible maximum of 48 g/kg/day. Hepatic steatosis was produced in 7/18 rats supplied ethanol in this fashion. Agar gels were also used to provide carbonyl iron to rats and it produced grade 3 to 4 hepatocyte iron loading in all study animals. The study demonstrates a practical method for administering ethanol and iron to rats without altering normal dietary intake. Ethanol supplied in this way does produce hepatic injury in the rat.


Computational quantification of patient-specific changes in ventricular dynamics associated with pulmonary hypertension.
Pulmonary arterial hypertension (PAH) causes an increase in the mechanical loading imposed on the right ventricle (RV) that results in progressive changes to its mechanics and function. Here, we quantify the mechanical changes associated with PAH by assimilating clinical data consisting of reconstructed three-dimensional geometry, pressure, and volume waveforms, as well as regional strains measured in patients with PAH (n = 12) and controls (n = 6) within a computational modeling framework of the ventricles. Modeling parameters reflecting regional passive stiffness and load-independent contractility as indexed by the tissue active tension were optimized so that simulation results matched the measurements. The optimized parameters were compared with clinical metrics to find usable indicators associated with the underlying mechanical changes. Peak contractility of the RV free wall (RVFW) γRVFW,max was found to be strongly correlated and had an inverse relationship with the RV and left ventricle (LV) end-diastolic volume ratio (i.e., RVEDV/LVEDV) (RVEDV/LVEDV)+ 0.44, R2 = 0.77). Correlation with RV ejection fraction (R2 = 0.50) and end-diastolic volume index (R2 = 0.40) were comparatively weaker. Patients with with RVEDV/LVEDV > 1.5 had 25% lower γRVFW,max (P < 0.05) than that of the control. On average, RVFW passive stiffness progressively increased with the degree of remodeling as indexed by RVEDV/LVEDV. These results suggest a mechanical basis of using RVEDV/LVEDV as a clinical index for delineating disease severity and estimating RVFW contractility in patients with PAH.NEW & NOTEWORTHY This article presents patient-specific data assimilation of a patient cohort and physical description of clinical observations.


Radioautographic investigation of gliogenesis in the corpus callosum of young rats. I. Sequential changes in oligodendrocytes.
The corpus callosum of young rats was examined to clarify the behavior of the three subtypes of oligodendrocytes (the large organelle-rich "light oligodendrocytes," the smaller and more densely stained cells referred to as "medium oligodendrocytes," and the even smaller and denser "dark oligodendrocytes"). It was hoped to find out whether cells of the three subtypes undergo division and how they are related to one another. 3H-thymidine was given intraperitoneally as single or three shortly spaced injections to a first group of 19- to 20-day old rats weighing about 40 g, and to a second group of 25-day old rats weighing about 80 g. The animals were sacrificed at various time intervals from 2 hours to 35 days after 3H-thymidine administration. Pieces of corpus callosum were taken near the superior lateral angle of the lateral ventricles; and semithin sections were radioautographed and stained with toluidine blue. Two hours after 3H-thymidine injection, label is virtually absent from light, medium and dark oligodendrocytes, from microglia, and probably from astrocytes, but is present in about 10% of the immature glial cells, which include the poorly differentiated glioblasts and the partially differentiated oligodendroblasts and astroblasts. Hence, the cells undergoing DNA synthesis and mitosis in the corpus callosum are these three types of immature cells. During the week that follow the administration of 3H-thymidine, label appears in oligodendrocytes and astrocytes, which presumably have arisen from the initially labeled immature cells. The oligodendrocytes acquire label in a sequential manner: the light cells show label first and their labeling index reaches a peak at the seven-day interval; the medium oligodendrocytes become labeled next with a labeling peak toward the 14- and 21-day intervals and, finally, the dark oligodendrocytes with a peak around the 28-day interval. Analysis by the method of Zilversmit et al. ('42-'43) provides precise details on the sequence: immature cells presumed to be oligodendroblasts give rise to light oligodendrocytes which, after four to seven days, transform into medium oligodendrocytes which, after another 11 to 18 days, transform into dark oligodendrocytes. The dark cells may persist indefinitely or turn over at a very slow rate. It is concluded that oligodendrocytes arise from the last division of oligodendroblasts and develop in three main periods: a light stage lasting less than a week, a medium stage lasting about two weeks, and a very long lasting dark stage.


Long-term inhibition of intestinal lipase by orlistat improves release of gut hormones increasing satiety in obese women.
Reduced postprandial secretion of peptide YY (PYY), glucagon-like peptide-1 (GLP-1), cholecystokinin, and increased hunger was reported after a single dose of orlistat, an inhibitor of intestinal lipase. As yet, the influence of long-term therapy with orlistat on PYYand GLP-1 release has not been studied. Our study was aimed at assessing the influence of 8-week therapy with orlistat as a component of a weight loss program on pre-prandial circulating PYY and GLP-1 levels. Forty obese women, without concomitant diseases, were randomly allocated to groups receiving orlistat or placebo during an 8-week weight management program. Body mass, body composition and plasma levels of PYY, GLP-1 and insulin (for QUICKI calculation) were determined prior to and at the end of therapy. Women treated with orlistat obtained significantly greater body and fat mass loss than those receiving placebo (9.0 ± 3.1 vs. 5.9 ± 3.2% and 21.9 ± 10.9 vs. 7.4 ± 15.6%, respectively). Only in those treated with orlistat a slight, but significant increase of the QUICKI was found (8.0 ± 16.5 vs. -0.1 ± 12.7 %, respectively). Weight loss was followed by a significant increase of plasma levels of PYY and GLP-1 in group treated with orlistat, and was about 2-times greater than receiving placebo. The increase was independent of body mass changes. The long-term inhibition of intestinal lipase by orlistat increases the pre-prandial levels of GLP-1 and PYY, independent of body mass changes. Therefore, it seems that long-term treatment with orlistat may exert hunger suppressing and insulin sensitizing incretin effect beyond weight reduction.


Gene transfer in primary cultures of human hepatocytes.
Using liposomes as the mediator of DNA transfer, we were successful in the transfection of human hepatocytes isolated from surgical samples with an E. coli beta-galactosidase gene (beta-gal). A comparison of transfection efficiency showed that of the four promoters used, cytomegalovirus (CMV) promoter yielded higher transfection efficiencies than Rous sarcoma virus (RSV), Simian virus-40 (SV-40) and human alpha-1 antitrypsin (AAT) promoters. These studies represent the first report on the successful transfection of primary cultures of human hepatocytes.


Dexmedetomidine restores autophagy and cardiac dysfunction in rats with streptozotocin-induced diabetes mellitus.
Dexmedetomidine (DEX), a highly selective and potent α2-adrenergic receptor agonist, has anti-apoptotic, anti-inflammatory, and anti-oxidative stress effects in diabetes mellitus (DM) rats. The underlying molecular mechanisms and signaling pathways of diabetic cardiomyopathy remain poorly understood. This study aimed to elucidate the effect of DEX on cardiac function in DM rats. Eight-week-old male Sprague Dawley rats were divided into three groups: control (n = 5), diabetes (DM, n = 7), and diabetes + DEX (DM + DEX, n = 10). DM was induced via intraperitoneal injection of streptozotocin (70 mg/kg); at 3 days later, DEX (1 µg/kg/h) was administered for 4 weeks. Cardiac function was evaluated using pressure-volume loop analysis and echocardiography. Left ventricular (LV) histological sections were used to analyze the interstitial collagen fraction. Using the LV samples, we performed a western blot analysis to evaluate signaling pathways and autophagic markers. The DM group had lower body weight and higher blood glucose level and heart weight/body weight ratio than the control group. However, metabolic changes did not differ between the DM and DM + DEX groups. Pressure-volume loop analysis and echocardiography showed impaired cardiac function, evidenced by a decrease in systolic and diastolic function, in both DM groups. DEX treatment in DM rats was associated with increased LV end-systolic pressure, LV contractility, cardiac output, and relaxed LV function compared with that in non-treated DM rats. LC3B and autophagy-related gene (ATG) proteins increased in the hearts of DM rats compared with the hearts of control rats. However, DEX reduced the expression of LC3B and ATG proteins in the hearts of DM rats. Increased p-ERK and decreased p-AKT were reduced in the hearts of DEX-treated DM rats. DEX reduces cardiac dysfunction and impaired autophagy in DM rats. This study reinforces our understanding of the potential anti-autophagic effect of DEX in patients with diabetic cardiomyopathy.


Myosin heavy chain isoform distribution in single fibres of bodybuilders.
The purpose of this study was to investigate the long-term effects of high intensity resistance training on myosin heavy chain (MHC) isoform composition of single fibres. Muscle biopsies were obtained from the right vastus lateralis of eight bodybuilders (BB) and seven physical education students (PES). Histochemical analyses were used to determine the fibre type distribution and the fibre cross-sectional area. MHC isoform composition of single fibres was determined with protein electrophoresis. The percentage of fibres expressing MHC IIA and MHC I/IIA was larger in BB (P < 0.05), while MHC IIX was completely absent (P < 0.05). In contrast, myofibrilar ATPase histochemistry only revealed a significantly lower percentage of type IIX fibres in BB (P < 0.05). The muscle fibre profile in the vastus lateralis muscle of BB may represent an adaptation based on the mechanical and biochemical demands of the long-term resistance training.


A review found heterogeneous approaches and insufficient reporting in overviews on adverse events.
To investigate reporting and methodological characteristics of overviews on adverse (drug-associated) events (AEs) of pharmacological interventions. We searched MEDLINE, Embase, Epistemonikos, and the Cochrane Database of Systematic Reviews from inception to May 17, 2021 for overviews exclusively investigating AEs of pharmacological interventions. We extracted general, reporting, and methodological characteristics and analyzed data descriptively. We included 27 overviews, 70% of which were published in 2016 or later. The most common nomenclature in the title was "overview" (56%), followed by "umbrella review" (26%). The median number of included systematic reviews (SRs) in each overview was 15 (interquartile range 7-34). Study selection methods were reported in 52%, methods for data extraction in 67%, and methods for critical appraisal in 63% of overviews. An assessment of methodological quality of included SRs was performed in 70% of overviews. Only 22% of overviews reported strategies for dealing with overlapping SRs. An assessment of the certainty of the evidence was performed in 33% of overviews. To ensure methodological rigor, authors of overviews on AEs should follow available guidance for the conduct and reporting of overviews.


The nature of ABH blood group antigens in human gastric secretion.
The origin of blood group ABH activity in human gastric content was investigated. Dialyzed and lyophilized samples of ten individual gastric secretions were assayed for ABH antigen under various conditions. The native activity persisted in delipidated residue of the respective secretions, but was completely missing in the lipid extracts of the analyzed samples. The alkaline degradation of the native and delipidated samples led to total loss of blood group activity of the analyzed materials, but no effect on A-active glycosphingolipid was evolved. Purified glycolipid portion of the lipid extract was lacking ABH activity and was shown to have distinct composition. This fraction contained only glyceroglucolipids and neither sphingosine nor other carbohydrates were present. On the basis of blood group activity assays of the native, delipidated, alkaline degraded samples and also on glycolipid analysis it was established that the ABH blood group activity of stomach secretion originated entirely from the glycoprotein portion of these samples.


Triglyceride, nonesterified fatty acids, and prediabetic neuropathy: role for oxidative-nitrosative stress.
Peripheral neuropathy develops in human subjects with prediabetes and metabolic syndrome before overt hyperglycemia. The contributions of impaired glucose tolerance and insulin signaling, hypertriglyceridemia and/or increased nonesterified fatty acids (NEFA), and hypercholesterolemia to this condition remain unknown. Niacin and its derivatives alleviate dyslipidemia with a minor effect on glucose homeostasis. This study evaluated the roles of impaired glucose tolerance versus dyslipidemia in prediabetic neuropathy using Zucker fatty (fa/fa) rats and the niacin derivative acipimox, as well as the interplay of hypertriglyceridemia, increased NEFA, and oxidative-nitrosative stress. Sixteen-week-old Zucker fatty rats with impaired glucose tolerance, obesity, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and increased NEFA displayed sensory nerve conduction velocity deficit, thermal and mechanical hypoalgesia, and tactile allodynia. Acipimox (100 mg kg(-1) day(-1), 4 weeks) reduced serum insulin, NEFA, and triglyceride concentrations without affecting glucose tolerance and hypercholesterolemia. It alleviated sensory nerve conduction velocity deficit and changes in behavioral measures of sensory function and corrected oxidative-nitrosative stress, but not impaired insulin signaling, in peripheral nerve. Elevated NEFA increased total and mitochondrial superoxide production and NAD(P)H oxidase activity in cultured human Schwann cells. In conclusion, hypertriglyceridemia and/or increased NEFA concentrations cause prediabetic neuropathy through oxidative-nitrosative stress. Lipid-lowering agents and antioxidants may find a use in the management of this condition.


A current and historical perspective on disparities in US childhood pneumococcal conjugate vaccine adherence and in rates of invasive pneumococcal disease: Considerations for the routinely-recommended, pediatric PCV dosing schedule in the United States.
Previous research has suggested that reducing the US 4-dose PCV13 schedule to a 3-dose schedule may provide cost savings, despite more childhood pneumococcal disease. The study also stressed that dose reduction should be coupled with improved PCV adherence, however, US PCV uptake has leveled-off since 2008. An estimated 24-36% of US children aged 5-19 months are already receiving a reduced PCV schedule (i.e., missing ≥1 dose). This raises a practical concern that, under a reduced, 3-dose schedule, a similar proportion of children may receive ≤2 doses. It is also unknown if a reduced, 3-dose PCV schedule in the United States will afford the same disease protection as 3-dose schedules used elsewhere, given lower US PCV adherence. Finally, more assurance is needed that, under a reduced schedule, racial, socioeconomic, and geographic disparities in PCV adherence will not correspond with disproportionately higher rates of pneumococcal disease among poor or minority children.


Why the Diagnosis of Attention Deficit Hyperactivity Disorder Matters.
Attention Deficit Hyperactivity disorder (ADHD) is one of the most common and challenging childhood neurobehavioral disorders. ADHD is known to negatively impact children, their families, and their community. About one-third to one-half of patients with ADHD will have persistent symptoms into adulthood. The prevalence in the United States is estimated at 5-11%, representing 6.4 million children nationwide. The variability in the prevalence of ADHD worldwide and within the US may be due to the wide range of factors that affect accurate assessment of children and youth. Because of these obstacles to assessment, ADHD is under-diagnosed, misdiagnosed, and undertreated. We examined factors associated with making and receiving the diagnosis of ADHD. We sought to review the consequences of a lack of diagnosis and treatment for ADHD on children's and adolescent's lives and how their families and the community may be involved in these consequences. We reviewed scientific articles looking for factors that impact the identification and diagnosis of ADHD and articles that demonstrate naturalistic outcomes of diagnosis and treatment. The data bases PubMed and Google scholar were searched from the year 1995 to 2015 using the search terms "ADHD, diagnosis, outcomes." We then reviewed abstracts and reference lists within those articles to rule out or rule in these or other articles. Multiple factors have significant impact in the identification and diagnosis of ADHD including parents, healthcare providers, teachers, and aspects of the environment. Only a few studies detailed the impact of not diagnosing ADHD, with unclear consequences independent of treatment. A more significant number of studies have examined the impact of untreated ADHD. The experience around receiving a diagnosis described by individuals with ADHD provides some additional insights. ADHD diagnosis is influenced by perceptions of many different members of a child's community. A lack of clear understanding of ADHD and the importance of its diagnosis and treatment still exists among many members of the community including parents, teachers, and healthcare providers. More basic and clinical research will improve methods of diagnosis and information dissemination. Even before further advancements in science, strong partnerships between clinicians and patients with ADHD may be the best way to reduce the negative impacts of this disorder.