Metformin alleviates glucolipotoxicity-induced pancreatic β cell ferroptosis through regulation of the GPX4/ACSL4 axis.
Ferroptosis, a new type of cell death, is associated with pancreatic β cell damage. However, the role of glucolipotoxicity in inducing β cell ferroptosis remains unclear. Metformin (Met), exenatide (Exe), and saxagliptin (Sax) are frequently used anti-hyperglycaemic drugs. However, their protective effects on β cells through ferroptosis modulation are not well-established. In this study, we observed significant ferroptosis in NIT-1 cells and primary mouse islets after exposure to high glucose and palmitate (HG/PA). Compared to Exe and Sax, Met significantly alleviated glucolipotoxicity-induced pancreatic β cell ferroptosis. Blocking the activity of glutathione peroxidase 4 (GPX4) with Ras-selective lethal 3 or inhibiting its expression by small interfering RNA transfection significantly attenuated the anti-ferroptosis effects of Met. Mechanistically, Met alleviates HG/PA-induced β cell ferroptosis by regulating the GPX4/ACSL4 axis. Collectively, our findings highlight the significance of ferroptosis in pancreatic β cell glucolipotoxicity-induced injury and provide novel insights into the protective effects of Met on islet β cells.


Epidemiological and Pathological Characterization of Feline Injection Site Sarcomas in Southern Brazil.
Feline injection site sarcoma (FISS) is a mesenchymal neoplasm with highly malignant characteristics. These tumours originate in anatomical sites where there has been previous parenteral administration of medicinal substances or implantation of medical devices. The aim of this study was to investigate the epidemiological and pathological features associated with FISS in the southern region of Brazil. The database of the Department of Veterinary Pathology of the Federal University of Rio Grande do Sul was searched for excisional and incisional biopsy samples compatible with FISS submitted between 2007 and 2017. Biopsy reports were reviewed and epidemiological information, including breed, age and sex of affected cats, as well as gross findings including anatomical location and size of the tumour and the presence of tissue invasion, were extracted. Eighty-nine samples were selected based on the established criteria. Most animals were of undefined breed and were female cats with a median age of 10 years. Grossly, 84.8% of the tumours were >2 cm in diameter. Regarding anatomical location, 34.9% of the tumours were located in the subcutaneous tissue of the thoracic wall, 29.2% in the flank, 21.3% in the interscapular region and 14.6% in the limbs. Histologically, the tumours originated in the subcutaneous tissue and were diagnosed as malignant mesenchymal neoplasms. Most were compatible with fibrosarcomas, but variants with features of pleomorphic sarcoma or chondrosarcoma were recognized. All tumours exhibited areas of necrosis and peripheral inflammatory infiltrate, composed predominantly of lymphocytes, plasma cells and macrophages. The results of this study suggest the need for dissemination of information on FISS epidemiology and guidelines for management of this tumour to veterinarians in the region.


[Physiology of transitory ischemic attacks in the vertebro-basilar region. I. Functional anatomy of the vertebro-basilar system].
Regions of supply by the posterior segment of the circle of Willis are discussed in terms of anatomo-functional organization.


[Vagus nerve stimulation for difficult to treat depression].
For the past 20 years vagus nerve stimulation (VNS) has been an approved invasive treatment option for treatment-resistant depression (TRD) across Europe. In contrast to more common treatments, such as ECT, knowledge about VNS is low both in the general population and among professionals. In this narrative review, we provide a clinically and scientifically sound overview of VNS. Hypotheses on the mechanism of action as well as the current evidence base on efficacy are presented. Perioperative management, adverse event profile and follow-up including dose titration are described. A comparison of international guideline recommendations on VNS is also provided. Furthermore, we formulate criteria that are helpful in the selection of appropriate patients. Electrical impulses are transmitted afferently via the vagus nerve and stimulate a neuromodulatory cerebral network via different pathways. Many studies and case series demonstrated the efficacy of VNS as an adjuvant procedure for TRD. The effect occurs with a latency period of 3-12 months and possibly increases with the duration of VNS. If stimulation recommendations are followed, side effects are tolerable for most patients. The use of VNS is an approved, effective and well-tolerated long-term therapy for chronic and treatment-resistant depression. Further sham-controlled studies over a longer observational period are desirable to improve the evidence.


Proteome identification of the silkworm middle silk gland.
To investigate the functional differentiation among the anterior (A), middle (M), and posterior (P) regions of silkworm middle silk gland (MSG), their proteomes were characterized by shotgun LC-MS/MS analysis with a LTQ-Orbitrap mass spectrometer. To get better proteome identification and quantification, triplicate replicates of mass spectrometry analysis were performed for each sample. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (Vizcaíno et al., 2014) [1] via the PRIDE partner repository (Vizcaino, 2013) [2] with the dataset identifier PXD003371. The peptide identifications that were further processed by PeptideProphet program in Trans-Proteomic Pipeline (TPP) after database search with Mascot software were also available in .XML format files. Data presented here are related to a research article published in Journal of Proteomics by Li et al. (2015) [3].


Expression of the Duchenne's muscular dystrophy gene in cultured muscle cells.
A partial cDNA clone for the Duchenne's muscular dystrophy (DMD) locus was used to investigate the expression of this locus in human muscle in vitro. Hybridization to a 14-kilobase RNA transcript was demonstrated in both fetal and mature human skeletal muscle and four lines of human muscle cells in culture. The DMD transcript was not detected in cultured cells outside the muscle lineage. In cultured muscle cells, gene expression was evident only in myotubes both before and after innervation with mouse spinal cord. Primary cultures of human myoblasts did not show the presence of the DMD transcript prior to fusion to form myotubes. An in vitro model is potentially an excellent system in which to investigate factors controlling expression of the DMD gene in normal muscle and how this expression is altered in cultured DMD muscle.


Axillary Response in Patients Undergoing Neoadjuvant Endocrine Treatment for Node-Positive Breast Cancer: Systematic Literature Review and NCDB Analysis.
Several studies have proven that neoadjuvant endocrine therapy (NET) has a similar beneficial therapeutic effect in estrogen-positive (ER+) breast cancer (BC) with improved breast conservation rate in patients undergoing NET versus neoadjuvant chemotherapy (NAC). The impact of axillary complete pathologic response (pCR) is less clear. We evaluate the impact of NET on axillary downstaging and surgical management. Using the National Cancer Database (NCDB), we identified all patients with node positive (N+), ER+, HER2- BC undergoing NET and performed a systemic review of literature using PRISMA guidelines. The literature review identified 1479 clinically N+ patients in four studies, 148 of whom had axillary pCR (10.0%). In the two studies of patients with invasive lobular carcinoma (ILC), 7.8% (69/883) of clinically N+ patients had axillary pCR. The NCDB query identified 4580 female patients with clinically N+ ER+ HER2- BC who underwent NET from 2010 to 2016 with mean age of 61.4 years. Patients who achieved a pCR were more likely to have N1 disease (p 0.008), moderately differentiated tumors (p 0.003), and ductal histology (p 0.04). There was no statistically significant difference in race, comorbidity score, education, income, hospital setting, or clinical tumor stage. Of the 4580 total patients, 663 (14.48%) had an axillary pCR (pN0) after NET, and 3917 (85.52%) remained pN+. We found that patients who underwent NET for N+ disease had a higher axillary pCR than previously reported (10%) in smaller studies. Although NET is not a common treatment option for women with N+ ER+ HER2- BC, it may be a suitable option for axillary downstaging, which is currently underutilized.


Calibration Factors for STS Risk Model Predictions: Why, How and When They Are Used.
The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database is the world's premier adult cardiac surgery outcomes registry. This tutorial explains the following: how STS updates the risk models that are used to calculate the predicted risks of adverse events in the registry; why STS on a quarterly basis adjusts or "calibrates" the observed-to-expected ratios to equal 1 (O/E = 1), thereby effectively making the annual number of adverse events predicted by the model match the annual number of adverse events observed in the entire registry; the differences between the calibrated and uncalibrated O/E ratios; and how and when to use each.


Short term supplementation rates to optimise vitamin E concentration for retail colour stability of Australian lamb meat.
The relationship between vitamin E supplementation rate and colour stability was investigated using 70 mixed sex 6-8 month old crossbred lambs. An initial group of 10 were slaughtered, while the remainder were fed a pellet ration containing either 30, 150, 275 or 400 IU vitamin E/kg ration or on green pasture for 56 days. After slaughter, carcases were halved; one side packed fresh (5 days) and the other in CO2 (21 days), both at 2°C. Five muscles were set for retail display for 96 h. The oxy/metmyoglobin ratio was measured every 12 h. Colour stability increased with increasing muscle vitamin E until an apparent maximum effect for vitamin E concentration (3.5-4.0mg α-tocopherol/kg tissue) was reached beyond which no further response was evident. This was reached within 3-4 weeks (275 IU treatment), and meat from these lambs should reach 60 h retail display with a satisfactory surface colour. This effect was most apparent in aerobic muscle types and meat aged post slaughter.


Anaerobic biodegradation of phenanthrene by a newly isolated nitrate-dependent Achromobacter denitrificans strain PheN1 and exploration of the biotransformation processes by metabolite and genome analyses.
Polycyclic aromatic hydrocarbons (PAHs) are widespread and harmful contaminants and are more persistent under anaerobic conditions. The bioremediation of PAHs in anaerobic zones has been enhanced by treating the contamination with nitrate, which is thermodynamically favourable, cost-effective, and highly soluble. However, anaerobic PAHs biotransformation processes that employ nitrate as an electron acceptor have not been fully explored. In this study, we investigated the anaerobic biotransformation of PAHs by strain PheN1, a newly isolated phenanthrene-degrading denitrifier, using phenanthrene as a model compound. PheN1 is phylogenetically closely related to Achromobacter denitrificans and reduces nitrate to nitrite (not N2 ) during the anaerobic phenanthrene degradation process. Phenanthrene biotransformation processes were detected using gas chromatography-mass spectrometry and were further examined by reverse transcription-quantitative PCR and genome analyses. Carboxylation and methylation were both found to be the initial steps in the phenanthrene degradation process. Downstream biotransformation processed benzene compounds and cyclohexane derivatives. This study describes the isolation of an anaerobic phenanthrene-degrading bacterium along with the pure-culture evidence of phenanthrene biotransformation processes with nitrate as an electron acceptor. The findings in this study can improve our understanding of anaerobic PAHs biodegradation processes and guide PAHs bioremediation by adding nitrate to anaerobic environments.


Increased platelet-fibrinogen interaction in patients with hypercholesterolemia and hypertriglyceridemia.
Binding of fibrinogen to platelets washed from the blood of patients with hypercholesterolemia and hypertriglyceridemia (n = 25) and control donors (n = 12) was compared. In addition, the content of platelet glycoprotein IIb was determined by radioimmunoassay. Fibrinogen was bound in significantly higher amounts (P < 0.02) to hyperlipidaemic platelets activated by ADP than to control ones (107,112 +/- 16,371 and 45,612 +/- 6495 molecules per platelet, respectively). The mean content of GPIIb was the same in hyperlipidaemic and in control platelets (2.06 +/- 0.16 and 1.94 +/- 0.21 micrograms/10(8) platelets, respectively). The amount of fibrinogen bound to the activated hyperlipidaemic platelets showed a positive correlation with total plasma cholesterol and LDL (r = 0.45 and 0.47, respectively) whereas a negative correlation with plasma HDL was found (r = -0.50). The increased expression of fibrinogen binding sites similar to that of hyperlipidaemic platelets could be produced by preincubation of normal platelets with palmitic acid. This was evidenced by a significant increase of fibrinogen binding sites in control platelets. This suggests that either palmitoylation of the receptor or microenvironment changes in the membrane lipid bilayer may be responsible for the enhanced platelet receptor capacity to bind fibrinogen.


Review on Alopecia Areata in the Middle East and Africa: Landscape and Unmet Needs.
Alopecia areata (AA) is an autoimmune disease characterized by non-scarring hair loss in adults and children. Clinical manifestations range from hair loss in small, well-circumscribed patches to total hair loss on the scalp or any other hair-bearing areas. Although the exact pathogenesis of AA is not fully understood, it is thought that loss of immune privilege caused by immunological dysregulation of the hair follicle is key. Genetic susceptibility also plays a role. Response to currently available treatments is widely variable, causing patient dissatisfaction and creating an unmet need. AA is frequently associated with multiple comorbidities, further affecting patient quality of life. AA causes a significant burden on dermatologists and healthcare systems in the Middle East and Africa. There is a lack of data registries, local consensus, and treatment guidelines in the region. Limited public awareness, availability of treatments, and patient support need to be addressed to improve disease management in the region. A literature review was conducted to identify relevant publications and highlight regional data on prevalence rates, diagnosis, quality of life, treatment modalities, and unmet needs for AA in the Middle East and Africa.


Serum ionized calcium by electrodes: new technology and methodology.
We report experience measuring serum ionized calcium (Ca2+) with new solid-state, specific calcium ion dip electrodes in a commercially available system for automated electrode measurments which permits stable measurements on thirty samples with up to six different electrodes simultaneously. The system provides electrostatic shielding, temperature regulation at 37degreeC, and adjustment of serum pH with CO2 gas, thereby making practical the use of serum standards and routine measurements on sera. When the electrodes are used with the rest of the measuring system and with serum standards, the system provides serum Ca2+ measurements with high precision (C.V. of 0.7%) and the calcium electrodes maintain good slopes for 50 to 150 hours of cumulative wet immersion. Response to new calcium activity is rapid, and wide variations in serum Ca2+ are readily measured.


5-Azacytidine increases the synthesis of embryonic hemoglobin (E2) in murine erythroleukemic cells.
The addition of 5-azacytidine to erythroleukemic cells which were induced to differentiate with DMSO or BA altered the expression of the hemoglobins. After the addition of 5-azacytidine there was an increase in hemoglobin synthesis especially in the embryonic E2 band. The beta-globin increased in synthesis after 5-azacytidine treatment. The level of hemoglobin synthesis in DMSO-induced cells is less than BA-induced cells while the effect of the 5-azacytidine stimulation was greater with DMSO induction than with BA induction.


Padovan numbers which are palindromic concatenations of two distinct repdigits.
In this paper we determine all Padovan numbers that are palindromic concatenations of two distinct repdigits.


Spatial and temporal expression of fibril-forming minor collagen genes (types V and XI) during fracture healing.
Skeletal development involves the coordinated participation of several types of collagen, including both major and minor fibrillar collagens. Although much is known about the major fibrillar collagens, such as types I and II, less is known about the minor fibrillar collagens, and their role in the repair and regeneration of bone has not been extensively studied. To clarify the role of minor fibrillar collagens in fracture repair, we examined the spatial and temporal expression of mRNAs for pro-alpha 2(V) collagen and pro-alpha 1(XI) collagen in healing fractures in the rat by in situ hybridization and compared their patterns of expression with those of mRNAs for pro-alpha 1(I) collagen, pro-alpha 1(II) collagen, and osteocalcin. A strong signal for pro-alpha 2(V) was detected in the periosteal osteoprogenitor cells, whereas osteocalcin mRNA was strongly expressed only in the deep layers of the hard callus. The distribution of the pro-alpha 2(V) signal was correlated with that of pro-alpha 1(I) but was mutually exclusive of that of pro-alpha 1(II). The expression of pro-alpha 1(XI) mRNA was synchronously regulated with that of pro-alpha 1(II) during chondrogenesis in the soft callus. In the hard callus, pro-alpha 1(XI) signal was found in osteoblastic cells at the site of intramembranous and endochondral ossification. These cells simultaneously expressed pro-alpha 2(V), although they were negative for pro-alpha 1(II). These findings suggest that the alpha 2(V) collagen chain participates in the formation of the noncartilaginous fibrillar network in the hard callus and preferentially contributes to the initial stage of the intramembranous bone formation. Recent reports have revealed that type-XI collagen, which had been classified as a cartilage-type collagen, is not necessarily specific for cartilage. The present results advanced this recognition and demonstrated a coexpression of alpha 1(XI) mRNA and alpha 2(V) mRNA in the noncartilaginous tissues in the fracture callus; this suggests the presence of tissue-specific and stage-specific heterotrimers consisting of alpha 1(XI) and alpha 2(V) collagen chains and the association of such hybrid trimers with the major fibrillar collagens in the process of fracture healing.


Genetic changes at specific stages of breast cancer progression detected by comparative genomic hybridization.
Although a simple linear progression model for breast cancer has already been proposed, its validity still remains controversial. Especially, the genetic and molecular features of breast cancer at different stages during the development and progression, as well as their relationship, have rarely been studied under the same experimental conditions simultaneously. According to these limitations in this research area, the current study applied comparative genomic hybridization technique to investigate genomic changes in 15 cases of breast atypical ductal hyperplasia (ADH), 15 cases of ductal carcinomas in situ (DCIS), and 15 cases of invasive ductal carcinomas (IDC) and the relationship among the genetic changes. Thirty commonly altered regions that were identified included known (gains of 1q,8q, 17q,20q,Xq and losses of 8p,13q,16q,17p,22q) and several uncharacterized (gains of 2q,5p, 10p,12q,16p,18q, etc. and losses of 11p13-pter,11q,14q,Xp, etc). The overall frequency of copy number losses was higher in IDC than that in DCIS (P = 0.013). ADH showed more frequent gain of 17q than that in IDC (P = 0.007), and IDC exhibited a higher frequency for the loss of 22q than that in ADH (P = 0.018). On one hand, several common genomic changes shared by ADH, DCIS, and IDC make a linear relationship for these three lesions possible. On the other hand, the heterogeneity has also showed clonal diversification and different pathways of breast cancer progression. The regions of chromosomal copy number alterations may bring new insights into the strategy for tumor progression blocking and the discovery of new potential targets for breast cancer treatment.


Pharyngeal airway changes associated with mandibular advancement.
This study analyzes changes in the anteroposterior dimension of the oropharynx as determined from lateral cephalometric radiographs on 26 patients who have undergone mandibular advancement. Increases in the sagittal dimensions of the oropharynx were unpredictable and tended to decrease with time, suggesting that mandibular advancement may be an unreliable method of treating obstructive sleep apnea. The most stable long-term results were found in those cases with narrowing of the oropharynx preoperatively.


A human monoclonal IgM lambda specific for an epitope shared by the 200 kDa neurofilament protein, histones and ribosomal proteins.
Serum monoclonal IgM lambda from a patient with axonal neuropathy reacted with axonal, nuclear, cytoplasmic and cell surface components by immunofluorescence. Experiments performed with Fab fragments of the monoclonal IgM proved that this reactivity was clearly due to actual antibody activity. Further study by Western blotting and ELISA showed that the IgM lambda reacted with the 200 kDa neurofilament protein, H1 and H2b histones and L14, L24 and L7 ribosomal proteins. This reactivity was abolished after adsorption either on purified 200 kDa neurofilament protein or on ribosomal proteins, demonstrating that these reactive proteins share a common epitope which possibly reflects sequence similarities. Sequence homology pointed to the involvement of the peptide AKSPEKAK in the epitope, and this was confirmed by dot blot analysis and adsorption experiments with this peptide. In addition, monoclonal IgM showed low level polyreactivity.


Treatment outcome of advance staged oral cavity cancer: concurrent chemoradiotherapy compared with primary surgery.
Concurrent chemoradiotherapy (CCRT) has been reported as effective and has become an acceptable treatment in advanced oral cancer. However, to date there is insufficient data to conclude that CCRT provides a good survival outcome. The purpose of this study was to compare survival rates and complications in patients with resectable advanced oral cavity squamous cell carcinoma treated with either CCRT or surgery with adjuvant radiotherapy (RT)/chemoradiotherapy (CRT). Stage III or IVa oral cavity carcinoma patients treated with curative intent by either CCRT or surgery with adjuvant RT were identified over a 7-year period (2009-2015). Survival rates and treatment complications were analyzed and compared between the two groups. 61 patients underwent CCRT and 128 patients underwent surgical excision and received postoperative RT. There was no statistically significant difference in survival outcome between the two treatment groups. 5-year overall survival rates (OS) were 33 versus 24% (P = 0.191) and the disease-specific survival rates (DSS) were 27 versus 25% (P = 0.857) when comparing the CCRT group and surgery with adjuvant RT/CRT group, respectively. Long-term complications were comparable between the two groups. CCRT has comparable survival outcome and complications for the treatment of advanced oral cavity squamous cell carcinoma, compared to surgery with adjuvant RT/CRT.


Unraveling neurotransmitter changes in de novo GBA-related and idiopathic Parkinson's disease.
Presently, neurotransmitter deficits in GBA-related Parkinson's disease (GBA-PD) and relationships with cognitive impairment are poorly understood. A better understanding of neurotransmitter impairments in GBA-PD - particularly in the newly diagnosed drug-naïve phase - may support developing targeted intervention strategies. We aimed to investigate patterns of neurotransmitter deficits in GBA-PD and idiopathic PD (iPD) and cognitive performance correlations. We recruited 189 newly diagnosed PD patients for GBA sequencing. Voxel-wise gray matter volume (GMV) was evaluated in a subgroup of 17 GBA-PD, 100 iPD, and 32 age- and sex-matched healthy controls (HCs). The JuSpace toolbox covering various neurotransmitter maps helped assess whether the spatial patterns of GMV alterations in GBA-PD or iPD patients (relative to HCs) were associated with specific neurotransmitter systems. GBA-PD patients indicated widespread GM atrophy in the fronto-temporal-occipital region compared with HCs. GMV atrophy was spatially correlated in GBA-PD and iPD with serotonergic, dopaminergic, and acetylcholinergic pathway distributions (p < 0.05, false discovery rate corrected). Executive function and language in cognitive domains were also associated with the strength of GMV colocalization of serotonergic, dopaminergic, and acetylcholinergic circuits. Regional GM atrophy related to specific neurotransmitter deficits in de novo GBA-PD and iPD patients could provide new insights into pathophysiological processes, facilitating potential therapeutic targets to support PD management.


Cochlear implantation in children with postlingual hearing loss.
Although it is clear that early auditory stimulation through cochlear implantation (CI) has been shown to improve speech and language development trajectories for children with prelingual hearing loss, data supporting implantation in postlingual children are mostly lacking. The purpose of this study was to characterize speech perception abilities following CI in a group of children with previously well-developed language abilities. Retrospective analysis. Twenty-eight hearing-impaired children who received CIs were selected for study based on the presence of well-developed spoken language skills before implantation. Fifteen children with prelingual hearing loss served as a control group. Speech perception skills were assessed using developmentally appropriate measures. Children with postlingual hearing loss showed a statistically significant improvement in open-set speech perception scores as early as 6 months following CI, whereas prelingual children demonstrated significant improvements only after 24 months of use. Despite these early disparities in performance, the two groups were similar 36 months after implantation and beyond (60 months of implant use). Children with well-developed language abilities before CI showed substantial (and statistically significant) early improvements in open-set speech perception abilities following implantation that continued beyond 2 years of follow-up. These results suggest that postlingual children are excellent candidates for CI.


The neuromuscular demands of toe walking: a forward dynamics simulation analysis.
Toe walking is a gait deviation with multiple etiologies and often associated with premature and prolonged ankle plantar flexor electromyographic activity. The goal of this study was to use a detailed musculoskeletal model and forward dynamical simulations that emulate able-bodied toe and heel-toe walking to understand why, despite an increase in muscle activity in the ankle plantar flexors during toe walking, the internal ankle joint moment decreases relative to heel-toe walking. The simulations were analyzed to assess the force generating capacity of the plantar flexors by examining each muscle's contractile state (i.e., the muscle fiber length, velocity and activation). Consistent with experimental measurements, the simulation data showed that despite a 122% increase in soleus muscle activity and a 76% increase in gastrocnemius activity, the peak internal ankle moment in late stance decreased. The decrease was attributed to non-optimal contractile conditions for the plantar flexors (primarily the force-length relationship) that reduced their ability to generate force. As a result, greater muscle activity is needed during toe walking to produce a given muscle force level. In addition, toe walking requires greater sustained plantar flexor force and moment generation during stance. Thus, even though toe walking requires lower peak plantar flexor forces that might suggest a compensatory advantage for those with plantar flexor weakness, greater neuromuscular demand is placed on those muscles. Therefore, medical decisions concerning whether to reduce equinus should consider not only the impact on the ankle moment, but also the expected change to the plantar flexor's force generating capacity.


Activity-dependent calcium transients in central nervous system myelinated axons revealed by the calcium indicator Fura-2.
Optical measurements from rat optic nerve, loaded with the new Ca2+ indicator Fura-2, provide the first evidence for the presence of activity-dependent fast intracellular [Ca2+] transients in mammalian central nervous system (CNS) myelinated axons. The results suggest that voltage-dependent Ca2+ channels are present in some of the myelinated axons. Optical measurements from axons stained with anterogradely transported voltage-sensitive dye suggest the presence of Ca2+-dependent potassium conductances in these axons. This report also demonstrates that Fura-2 can readily detect changes in [Ca2+] inside cells as a result of electrical activity, and establishes its suitability for measurements of intracellular Ca2+ transients in the millisecond time domain.


Sirolimus inhibits human pancreatic carcinoma cell proliferation by a mechanism linked to the targeting of mTOR/HIF-1 alpha/VEGF signaling.
Sirolimus(SRL, Rapamune(â), rapamycin) is a highly specific inhibitor of mammalian target of rapamycin (mTOR). Sirolimus exerts its biological activity by inhibiting the serine-threonine kinase mammalian target of rapamycin (mTOR), which regulates important cellular processes such as control of cell cycle, cell size, translation initiation and transcription. The ability of sirolimus to inhibit cancer cell proliferation has led to efforts to develop rapamycin and related mTOR inhibitors as anticancer agents. Here, we made mTOR as a controlling target, using a new immunosuppressant named sirolimus, to investigate the inhibitory effects of sirolimus on cell proliferation and the expression of mTOR, Hypoxia-inducible factor-1 alpha(HIF-1alpha) and vascular endothelial growth factor (VEGF) in human pancreatic carcinoma SW1990 cell line. Sirolimus is effective in vivo against pancreatic carcinoma and demonstrates that the effect of sirolimus on the inhibition of tumor cell proliferation is associated with the suppression of the mTOR/HIF-1alpha/vascular endothelial growth factor (VEGF) pathway. Thus, the targeting of mTOR signaling has been exploited as a novel therapy for human cancers.


Influence of ionic interactions on essential oil and phenolic diterpene composition of Dalmatian sage (Salvia officinalis L.).
The potential of four essential cations (K(+), Ca(2+), Mg(2+) and Fe(2+)) to alleviate salt toxicity was studied in sage (Salvia officinalis L.) plants grown in pots. Two concentrations of the following chloride salts: KCl, CaCl₂, MgCl₂ and FeCl₃, were used together with 100mM NaCl to study the effects of these nutrients on plant growth, leaf essential oils (EOs) and phenolic diterpenes composition. The sage plants accumulated Na(+) in their leaves (includers); this has affected secondary metabolites' biosynthesis. Treatment with 100mM NaCl slightly decreased borneol and viridiflorol, while increased manool concentrations. Addition of KCl, CaCl₂ and MgCl₂ increased considerably in a dose-dependent manner the oxygen-containing monoterpenes (1.8-cineole, camphor, β-thujone and borneol) in 100mM NaCl-treated sage. Whereas, the contents of viridiflorol decreased further with the addition of KCl in 100mM NaCl-treated sage. Our results suggest that the changes in EOs composition were more related to K(+) and Ca(2+) availability than to Na(+) toxicity. Furthermore, treatment with NaCl decreased by 50% carnosic acid (CA), a potent antioxidant, content in the leaves. K(+) and Ca(2+) promoted the accumulation of CA and its methoxylated form (MCA) in the leaves. The concentration of CA was positively correlated with leaf K(+) (r=0.56, P=0.01) and Ca(2+) (r=0.44, P=0.05) contents. It appears that different salt applications in combination with NaCl treatments had a profound effect on EOs and phenolic diterpene composition in sage. Therefore, ionic interactions may be carefully considered in the cultivation of this species to get the desired concentrations of these secondary metabolites in leaf extracts.


Carbonic anhydrase inhibitors: inhibition of the human isozymes I, II, VA, and IX with a library of substituted difluoromethanesulfonamides.
An inhibition study of the human cytosolic isozymes I, and II, the mitochondrial isoform VA, and the tumor-associated, transmembrane isozyme IX of carbonic anhydrase (CA, EC 126.96.36.199) with a library of aromatic/heteroaromatic/polycyclic difluoromethanesulfonamides is reported. Most of the inhibitors were derivatives of benzenedifluoromethanesulfonamide incorporating substituted-phenyl moieties, or were methylsulfonamide and difluoromethyl-sulfonamide derivatives of the sulfamates COUMATE and EMATE, respectively. Except for the methylsulfonamide-COUMATE derivative which behaved as a potent CA II inhibitor (K(I) of 32nM), these sulfonamides were moderate inhibitors of all isozymes, with inhibition constants in the range of 96-5200nM against hCA I, of 80-670nM against hCA II, and of 195-9280nM against hCA IX, respectively. Remarkably, some derivatives, such as 3-bromophenyl-difluoromethanesulfonamide, showed a trend to selectively inhibit the mitochondrial isoform CA VA, showing selectivity ratios for inhibiting CA VA over CA II of 3.53; over CA I of 6.84 and over CA IX of 9.34, respectively, although it is a moderate inhibitor (K(I) of 160nM). Some of these derivatives may be considered as leads for the design of isozyme selective CA inhibitors targeting the mitochondrial isozyme CA VA, with potential use as anti-obesity agents.


Event-related potential correlates of primed and unprimed words in children co-morbid for disruptive behaviour disorders and academic delay.
Children with disruptive behaviour disorders and academic delay (DD-AD) were compared to children with disruptive behaviour disorders only (DD) and normal control children with no psychiatric disturbance or academic delay (NO) with respect to scalp-recorded event-related electrical potentials (ERPs) elicited by semantically primed and unprimed words. Primed words were preceded by spoken words having a related meaning, while unprimed words were preceded by nonassociated spoken words. For normal controls, the unprimed words elicited greater N400 amplitudes at frontal-central recording sites than primed words. Primed vs. unprimed N400 differences were not evident at frontal sites in DD and the DD-AD group failed to exhibit differences in primed vs. unprimed N400 amplitudes at either frontal, central or parietal sites. These findings suggest that DD-AD children may represent a unique neuroelectric subgroup of learning disabilities.


Magnitude and Determinants of Syphilis and HIV Co-Infection Among Female Sex Workers in Ethiopia: Evidence from Respondent Driven Samples, 2019-2020.
Female sex workers (FSWs) play an important role in transmitting Human Immunodeficiency Virus (HIV) and syphilis from high-risk groups to the general population. Syphilis and HIV infections are generally more prevalent among FSWs. However, in Ethiopia, up-to-date evidence about Syphilis-HIV co-infections among FSWs was lacking. To determine the magnitude and determinants of Syphilis-HIV co-infection among FSWs in Ethiopia, 2019-2020. A cross-sectional HIV and other sexually transmitted infections Bio-Behavioral Survey (HSBS) was conducted using respondent-driven sampling (RDS) among 6,085 FSWs in Ethiopia from August 2019 to January 2020. Data was collected, merged with laboratory data, and analyzed in R software using the RDS package. The odds ratio was calculated at 95% CI to measure associations between the dependent and independent variables. Variables that yield p<0.25 in univariate analysis were included in multivariate analysis. In multivariate analysis, variables with p<0.05 were declared as statistically significant. Results were presented in frequency tables and charts. The prevalence of Syphilis-HIV co-infection among FSWs was 2.9% [95% CI=2.6-3.2]. Age of the FSWs (15-19 years old (AOR=0.03; 95% CI=0.01-0.12)), non-formal educational level (AOR=3.18; 95% CI=1.78-5.68), monthly income <2,500 ETB (AOR=3.05; 95% CI=1.45-6.42), major depression (AOR=1.85; 95% CI=1.18-2.89), forced first sex experience (AOR=1.71; 95% CI=1.2-2.44), condom breakage (AOR=1.62; 95% CI=1.14-2.30), Hepatitis B seropositivity (AOR=2.32; 95% CI=1.10-4.90), and Hepatitis C seropositivity (AOR=5.37; 95% CI=1.70-16.93) were strongly associated with Syphilis-HIV co-infection among FSWs in Ethiopia. The prevalence of Syphilis-HIV co-infection among FSWs in Ethiopia was high. To ward off Syphilis-HIV co-infection among FSWs, a special FSWs-targeted HIV and Syphilis/STIs prevention program and treatment approach needs to be devised. An outreach approach to address the sexual and reproductive health needs of FSWs has to be part of the strategy.


Benzimidazole condensed ring systems 10 (1). Synthesis and cytotoxic activity of some pyrido[1,2-a]benzimidazoles.
As a part of research project on the synthesis of a number of pyrido[1,2-a]benzimidazole derivatives with possible antineoplastic activity and as a result of the interesting antineoplastic activity recorded for one such compounds (NSC 649900), some new pyrido[1,2-a]benzimidazoles were prepared and evaluated for such activity. Compound (11, NSC 660334) exhibited a moderate in vitro antineoplastic activity especially against most of the leukemia cell lines, while compound (10, VM30309) showed a good cytotoxic activity against Artina salina larvae (IC50 = 1.75 micrograms/ml).


Combined effect of nonionic surfactant Tween 80 and DOM on the behaviors of PAHs in soil--water system.
Batch experiments were performed to examine the desorption behavior of phenanthrene and pyrene in soil-water system in the presence of nonionic surfactant Tween 80 and dissolved organic matter (DOM) derived from pig manure or pig manure compost. Addition of 150 mgl(-1) Tween 80 desorbed 5.8% and 2.1% of phenanthrene and pyrene from soil into aqueous phase, respectively, while the addition of both Tween 80 and DOM derived from pig manure compost and pig manure could further enhance the desorption of phenanthrene to 15.8% and 16.2%, respectively, and 6.4% and 10.9%, respectively, for pyrene. In addition, our finding also suggested that subsequent addition of Tween 80 into the soil-water system could further enhance PAHs desorption. The enhancement effect of the co-existence of Tween 80 and DOM was more than the additive effect of the Tween 80 and DOM individually. It is likely that the formation of DOM-surfactant complex in the soil-water system may be a possible reason to explain such desorption enhancement phenomenon. Therefore, it is anticipated that the coexistence of both Tween 80 and DOM derived from pig manure or pig manure compost in soil environment will enhance the bioavailability of PAHs as well as other hydrophobic organic contaminants (HOCs) by enhancing the desorption during remediation process.


Personalised antimicrobial dosing: standing on the shoulders of giants.
Suboptimal use of antimicrobial drugs contributes to increasing antimicrobial resistance and may lead to therapeutic failure at the individual patient level. Considering the significant pharmacokinetic (PK) variation in special patient populations and the variability in pathogen susceptibility, personalised dosing of antimicrobial drugs is pivotal. Dosing based on PK and pharmacodynamic properties of antibiotics guided by therapeutic drug monitoring (TDM) maximises efficacy and minimises toxicity for individual patients. Model-informed precision dosing (MIPD) provides a means of predicting drug response and dose requirements in individual patients based on individual patient and pathogen characteristics. Clear concentration targets should be defined to make use of MIPD and TDM in clinical practice. Target selection, validation and publication in the drug label should be part of drug licensing.


Learning to smell: repeated exposure increases sensitivity to androstenone, a major component of boar taint.
This study aimed to assess whether repeated exposure affects subjects' ability to detect androstenone. Olfactory acuity of 77 female and 44 male subjects (age 37.5 ± 11.7 years) was assessed three times during six weeks. Replicate triangle tests using various dilutions of androstenone (0.5, 5.0, and 50.0 μg/g) on filter paper smell strips were applied. Subjects were either assigned to a test group (TRAIN) using androstenone for daily training, or to a control group (CONTR) using a placebo. For the low, the intermediate, and the high level of androstenone presented, detection rate increased from 14.1 to 30.6%, 40.5 to 62.8%, and 65.3 to 78.5% respectively within 6 weeks from the initial assessment. Results suggest that mere exposure during repeated olfactory testing increased subjects' ability to correctly discriminate androstenone. The olfactory improvement was, however, more pronounced in the TRAIN group. Androstenone detection appears to be associated with its individual appreciation.


An efficient nickel-catalyzed alkenylation of functionalized benzylic halides with alkenylaluminum reagents.
Highly efficient and simple coupling reactions of benzylic bromides or chlorides with alkenylaluminum reagents catalyzed by NiCl(2)(PPh(3))(2) are reported. The coupling reactions proceed effectively at room temperature employing low loading of catalyst, 0.5 mol% for benzylic bromides having either electron-donating or -withdrawing substituents on the aromatic ring, affording coupling products in excellent yields of up to 94% in short reaction times. The coupling reactions of benzylic chloride require 5 mol% of the catalyst and a longer reaction time of 2 h.


Property-enhanced paraffin-based composite phase change material for thermal energy storage: a review.
Research on phase change material (PCM) for thermal energy storage is playing a significant role in energy management industry. However, some hurdles during the storage of energy have been perceived such as less thermal conductivity, leakage of PCM during phase transition, flammability, and insufficient mechanical properties. For overcoming such obstacle, researchers have been concentrating on composite PCM, where PCM is combined with metal or non-metal particles, fibrous materials, expanded or porous materials, and flame retardants. The main purpose of the current paper is to review the properties enhanced paraffin-based composite PCM. In the literature review, paraffin is selected as a thermal energy storage material, which is mixed with property-enhancing material to prepare composite. Structural and thermal properties of composite have been explored with the help of scanning electron microscope, X-ray diffractometer, transmission electron microscope, polarizing optical microscope, Fourier transform infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry. Mechanical properties of the material are also portrayed using different testing techniques. Nevertheless, numerical methods have also been adopted for characterization of composite. It is found from the literature review that with incorporation of property-enhancing material, thermal conductivity, phase transition rate, and shape stability of PCM increased at the same time flammability, heat storage capacity, and mechanical properties reduced.


Production of cyclopentanone from furfural over Ru/C with Al11.6PO23.7 and application in the synthesis of diesel range alkanes.
The bio-based platform molecule furfural was converted to the high value chemical cyclopentanone over Ru/C (0.5 wt%) and Al11.6PO23.7 catalysts in good yield (84%) with water as the medium. After screening the reaction conditions, the selectivity for cyclopentanone and cyclopentanol could be controlled by adjusting the hydrogen pressure at the temperature of 433 K. Herein, we propose a new mechanism for the synergistic catalysis of a Bronsted acid and Lewis acid for the conversion of furfural to cyclopentanone through the cyclopentenone route, which is catalyzed by Ru/C and Al11.6PO23.7. In addition, based on cyclopentanone, higher octane number cyclic alkanes (>85% selectivity), which are used as hydrocarbon fuels, were synthesized via a C-C coupling reaction followed by hydrodeoxygenation.


Autosomal recessive Oliver-McFarlane syndrome: retinitis pigmentosa, short stature (GH deficiency), trichomegaly, and hair anomalies or CPD syndrome (chorioretinopathy-pituitary dysfunction).
We describe a brother and sister with retinitis pigmentosa (RP), growth failure, long eyelashes, and sparse hair. They were born to young healthy consanguineous parents and presented at birth with IUGR. Evolving pigmentary retinopathy was diagnosed at the age of 5 years. A similar condition (Oliver-McFarlane) syndrome was reported previously. Our two sibs confirm the existence of this autosomal recessive syndrome.


Impact of land-use dynamics and climate change scenarios on Groundwater recharge in the case of Anger watershed, Ethiopia.
An assessment of land use dynamics and climate variability impacts on hydrological processes is vital and a prerequisite for effective water resources management. This study aimed to quantify the effect of land-use changes and long-term climate variability on the Anger watershed's annual groundwater recharge, which covers a total drainage area of 7717 km2. The WetSpass (Water and Energy Transfer between Soil, Plants, and Atmosphere under quasi-Steady State) model was used to investigate the impact of land cover and climate variability on groundwater. The Mann-Kendall (MK) test was used to analyze the spatial variations and temporal trends of the climate variables in the watershed. Input data for the model, such as land use, hydro-meteorological data, soil texture, topography, and groundwater elevation parameters, were prepared in the form of gridded maps with a 30 m resolution. The model results indicate that land-use change and climate variability considerably impact distributed groundwater recharges. Groundwater recharge decreased with land use in 2000 and 2019, respectively, as compared to baseline land usage (1985). The study also demonstrates how the anticipated future combination of less precipitation and higher temperatures has a detrimental effect on the watershed's annual average groundwater recharge. Future rising temperatures and reduced precipitation are projected to result in an average annual groundwater recharge showing significant decreases in 2050, 2080, and 2110, respectively, according to scenario-based models. The result has provided valuable information on the management and response of groundwater recharge to climate and land-use changes, particularly for the Anger watershed and for the total country as well.


Greenhouse gases emissions from duckweed pond system treating polyester resin wastewater containing 1,4-dioxane and heavy metals.
Phytoremediation of polyester resin wastewater containing 1,4-dioxane and heavy metals using Lemna gibba (L.gibba) was enhanced by incorporation of perforated polyethylene carrier materials (PCM) onto the duckweed pond (DWP) system. The DWP module was operated at a hydraulic retention times (HRTs) of 2, 4 and 6 days and as well as 1,4-dioxane loading rate of 16, 25 and 48 g/m3.d. The maximum removal efficiency of 54 ± 2.5% was achieved for 1,4-dioxane at an HRT of 6 days and loading rate of 16 g1,4-dioxane/m3.d. Similarly, the DWP system provided removal efficiencies of 28.3 ± 2.1, 93.2 ± 7.6, 95.7 ± 8.9 and 93.6 ± 4.9% for Cd2+, Cu2+, Zn2+ and Ni2+ at influent concentration of 0.037 ± 0.01, 1.2 ± 0.9, 27.2 ± 4.7 and 4.6 ± 1.2 mg/L respectively. The structural analysis by Fourier-transform infrared spectroscopy (FTIR) clearly displayed a reduction of 1,4- dioxane in the treated effluent. A strong peak was detected for L. gibba plants at frequency of 3417.71 cm-1 due to N-H stretching, which confirm the proposed mechanism of partially conversion of 1,4-dioxane into amino acids. Glycine, serine, aspartic, threonine and alanine content were increased in L. gibba by values of 35 ± 2.2, 40 ± 3.2, 48 ± 3.7, 31 ± 2.8, and 56 ± 4.1%, respectively. The contribution of DWP unit as a greenhouse gases (GHG) emissions were relatively low (1.65 gCO2/Kg BODremoved.d., and 18.3 gCO2/Kg biomass.d) due to photosynthesis process, low excess sludge production and consumption of CO2 for nitrification process (1.4 gCO2/kgN removed.d). Based on these results, it is recommended to apply such a technology for treatment of polyester resin wastewater containing 1,4-dioxane and heavy metals at a HRT not exceeding 6 days.


Necrotic arachnidism in the northwest United States and its probable relationship to Tegenaria agrestis (Walckenaer) spiders.
Necrotic spider bites in the states of Washington, Oregon and Idaho, U.S.A., have become increasingly frequent during the past decade. The great majority of cases seen by physicians are tentatively diagnosed as 'brown recluse' spider bite on the basis of clinical manifestations. However, investigation of over 30 such cases from several northwest localities has revealed that Tegenaria agrestis, a spider introduced into the northwest U.S. from Europe, is almost invariably found at the locality where the bite probably occurred. Necrotic arachnidism was seen only in areas where populations of Tegenaria agrestis spiders were well established and did not occur where Tegenaria agrestis was absent. The geographical spread of Tegenaria agrestis spiders parallels the appearance of necrotic arachnidism in several areas. Evaluation of some individual cases strongly implicates Tegenaria agrestis as the responsible organism and Tegenaria agrestis is likely responsible for the majority of 'brown recluse' spider bites seen in the northwest U.S. Tegenaria agrestis should now be considered a species of clinical significance capable of producing marked dermal lesions and, not infrequently, severe toxicosis in humans. Case histories are presented and manifestations of poisoning are described.


An integrated platform for simultaneous multi-well field potential recording and Fura-2-based calcium transient ratiometry in human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes.
Human induced pluripotent stem cell-derived cardiomyocytes are available from various sources and they are being evaluated for safety testing. Several platforms are available offering different assay principles and read-out parameters: patch-clamp and field potential recording, imaging or photometry, impedance measurement, and recording of contractile force. Routine use will establish which assay principle and which parameters best serve the intended purpose. We introduce a combination of field potential recording and calcium ratiometry from spontaneously beating cardiomyocytes as a novel assay providing a complementary read-out parameter set. Field potential recording is performed using a commercial multi-well multi-electrode array platform. Calcium ratiometry is performed using a fiber optic illumination and silicon avalanche photodetectors. Data condensation and statistical analysis are designed to enable statistical inference of differences and equivalence with regard to a solvent control. Simultaneous recording of field potentials and calcium transients from spontaneously beating monolayers was done in a nine-well format. Calcium channel blockers (e.g. nifedipine) and a blocker of calcium store release (ryanodine) can be recognized and discriminated based on the calcium transient signal. An agonist of L-type calcium channels, FPL 64176, increased and prolonged the calcium transient, whereas BAY K 8644, another L-type calcium channel agonist, had no effect. Both FPL 64176 and various calcium channel antagonists have chronotropic effects, which can be discriminated from typical "chronotropic" compounds, like (±)isoprenaline (positive) and arecaidine propargyl ester (negative), based on their effects on the calcium transient. Despite technical limitations in temporal resolution and exact matching of composite calcium transient with the field potential of a subset of cells, the combined recording platform enables a refined interpretation of the field potential recording and a more reliable identification of drug effects on calcium handling.


A meta-ethnographic synthesis of fathers' experiences of complicated births that are potentially traumatic.
birth is a natural and for many, life enhancing phenomenon. In rare circumstances however birth can be accompanied with complications that may place the mother and infant at risk of severe trauma or death. Witnessing birth complications or obstetric emergencies can be distressing and potentially traumatic for the father. the aim of this paper is to report on the findings of a meta-ethnographic synthesis of father's experiences of complicated births that are potentially traumatic. databases searched included CINAHL, Scopus, PubMed and PsycINFO with Full Text. The search was conducted in February and March 2013 and revised in February 2015 for any new papers, and the search was limited to papers published in English, full text and peer-reviewed journals published between January 2000 to December 2013. studies were included if they focused on fathers/men's experiences of witnessing a birth with complications including a caesarean section or an adverse obstetric event. Studies included needed to use qualitative or mixed methods research designs with a substantial qualitative component. ANALYTIC STRATEGY: a meta-ethnographic approach was used using methods of reciprocal translation guided by the work of Noblit and Hare (1988) on meta-ethnographic techniques. Quality appraisal was undertaken using the Critical Appraisal Skills Programme (CASP) tool. eight qualitative studies with a total of 100 participants were included in the final sample. The men ranged in age from 19 to 50 years. Four major themes were identified: 'the unfolding crisis', 'stripped of my role: powerless and helpless', 'craving information' and 'scarring the relationship'. Participants described the fear and anxiety they felt as well as having a sense of worthlessness and inadequacy. Men did not receive sufficient information about the unfolding events and subsequently this birth experience impacted on some men's interactions and relationships with their partners. witnessing a complicated or unexpected adverse birth experience can be distressing for men and some may report symptoms of birth trauma. Being informed by and receiving support from midwives and other health professionals appears to help mitigate the negative impact of birth complications. Effective support may help address men's confusion about their role, however genuinely including men as recipients of care or service in pregnancy, labour and birth raises important questions about whether the father is also a recipient of maternity care and if the transition to fatherhood is itself becoming a medical event?


Employing molecular, chemical and physiological techniques using Crassostrea virginica to assess ecosystem health along coastal South Carolina and North Carolina, United States.
Natural and anthropogenic environmental impacts can introduce contaminants into sensitive habitats, threatening ecosystems and human health. Consistent monitoring of coastal areas provides critical environmental assessment data. Sediments and Eastern Oyster (Crassostrea virginica) tissues were collected at fourteen South Carolina (SC) and four North Carolina (NC) sites as part of the National Oceanic and Atmospheric Administration's Mussel Watch environmental monitoring program. Cellular and molecular techniques were employed to measure C. virginica stress response, specifically, Lipid Peroxidation (LPx), Glutathione (GSH), and qPCR techniques. Gene specific primers targeted for detecting oxidative stress and cellular death were developed in C. virginica to gauge response to current environmental conditions using gill and hepatopancreas (HP) tissue. In order to validate gene specific markers as additional assessment tools, a 96 h zinc (Zn) laboratory exposure was performed. Cellular biomarker data revealed tissue specific responses. Hepatopancreas data showed C. virginica exhibited stress through the lipid peroxidation assay amongst sampling sites, however, response was managed through glutathione detoxification. Gill tissue data had significantly lower levels of cellular biomarker response compared to hepatopancreas. Molecular biomarkers targeting these cellular stress pathways through qPCR analysis show upregulation of Metallothionein in hepatopancreas and gill tissue with a concurrent > 2-fold upregulation in the detoxification marker Superoxide Dismutase (SOD) at three NC sites. SC sites displayed higher stress levels through LPx assays and down-regulation in GPx gene activity. Laboratory zinc exposure revealed no significance in cellular biomarker results, however, molecular data showed gills responding to zinc treatment through upregulation of Metallothionein, SOD and Cathepsin L, indicating an acute response in gills. Collectively, chemical, cellular and molecular methods clarify sentinel stress response of biological impacts and aid in evaluating environmental health in coastal ecosystems. This combined methodological approach provides a detailed analysis of environmental conditions and improves land-use management decisions.


Role of Negative-Pressure Wound Therapy in the Management of Submandibular Fistula After Reconstruction for Osteoradionecrosis.
Although negative-pressure wound therapy (NPWT) for complicated wounds has been extensively studied, it is rarely used in cases involving a submandibular fistula due to radiation-induced osteoradionecrosis of the mandible. This study aimed to investigate the efficacy of NPWT for submandibular fistulas after reconstruction for osteoradionecrosis. Nine patients with submandibular fistulas after reconstruction for osteoradionecrosis treated with NPWT between 2011 and 2014 were included in the study. The wound healing was documented. The NPWT device was removed postoperatively between days 7 and 12 (mean duration, 9.6 days). The wound bed was filled with healthy granulation tissue, and successful healing by second intention was observed in all patients within 2 weeks. No complications were observed. The follow-up ranged from 4 to 27 months (mean, 18 months); the fistulas exhibited excellent healing, and no recurrence or infection was observed. NPWT is a safe, effective technique for managing submandibular fistulas after reconstruction for osteoradionecrosis.


Maternal age and incidence of low birth weight at term: a population study.
A total of 184,567 singleton live births with gestational ages of 40 weeks were examined from the 1980-1984 Illinois birth certificate data to determine the independent effect of maternal age on the incidence of low birth weight at term. The incidence is highest in mothers less than 17 years of age (3.2%) and gradually declines with advancing maternal age to reach 1.3% in women aged 25 to 34 years. It increases to 1.7% for those greater than 35 years of age. To separate out the independent effect of maternal age on the incidence of low birth weight infants at term, the presence of other maternal factors, such as race, education, parity, marital status, and prenatal care, were adjusted by use of a series of multiple logistic regression analyses. All of these analyses consistently demonstrated that the adjusted risk for low birth weight at term is the lowest in teenagers and increases with advancing maternal age. These results indicate that the high incidence of this factor in young mothers apparently reflects their poor sociodemographic and prenatal care status. Advancing maternal age is associated with a decreased potential for fetal growth, possibly reflecting biologic aging of maternal tissues and systems or the cumulative effects of disease.


A mouse model for tracking nigrostriatal dopamine neuron axon growth.
The midbrain dopaminergic system, which consists of neurons of the substantia nigra and the ventral tegmental area, is a subject of intense interest, since the loss of neurons from the substantia nigra results in motor disorders characteristic of Parkinson's disease. We have generated a knock-in reporter mouse line with the tau-lacZ fusion gene inserted into the Pitx3 locus via homologous recombination. This approach permitted the visualisation of midbrain specific dopaminergic axonal tracts from both the substantia nigra and the ventral tegmental area in phenotypically normal heterozygous Pitx3-taulacZ brain tissues, either in situ or following culture in vitro, by a simple and sensitive beta-galactosidase enzyme reaction. Thus the Pitx3-taulacZ mice could serve as a valuable tool for the identification of molecules regulating midbrain dopaminergic neuritogenesis, either in vivo in combination with genetic manipulation in mice, or in vitro using organ cultures.


Urinary Biomarkers for Prostate Cancer.
In light of the overdiagnosis and overtreatment associated with widespread prostate-specific antigen-based screening, controversy persists surrounding the detection and diagnosis of prostate cancer (PCa). Given its anatomic proximity to the prostate, urine has been proposed as a noninvasive substrate for prostatic biomarkers. With greater understanding of the molecular pathways of carcinogenesis and significant technological advances, the breadth of potential biomarkers is substantial. In this review, the authors aim to provide an evidence-based assessment of current and emerging urinary biomarkers used in the detection and prognostication of PCa and high-grade PCa, with particular attention on clinically relevant findings.


The diagnostic yield of CT-guided percutaneous lung biopsy in solid organ transplant recipients.
Despite the widespread use of computed tomography(CT)-guided percutaneous lung biopsy (PLB) in immunocompetent patients, the diagnostic yield and safety in solid organ transplant (SOT)recipients is unknown. The purpose of this investigation was to determine the test performance of CT-PLB in SOT recipients. We performed a 10-yr single-center, retrospective analysis among heart, lung, kidney, and liver transplant recipients. We included all adult patients who underwent a PLB of a parenchymal lung nodule following their transplantation. Within the study period, 1754 SOTs were performed, of which 45 biopsies met study criteria. Overall, the incidence of PLB in SOT was 3%.PLB established a diagnosis in 24 of 45 cases. The yield of PLB was better for combined biopsy technique (fine-needle aspiration biopsy [FNAB]) and core biopsy than for FNAB alone (odds ratio [OR]: 4.2, 95% confidence interval [CI]: 1.2, 15.6), and for lesions that were malignant (OR: 10.0, 95%CI: 1.8, 75.4) or caused by an invasive fungal infection (OR: 5.0, 95% CI:1.1, 27.9). Complications occurred in 13% (6/45) of patients. CT-guided PLB is a safe modality that provides a moderate yield for diagnosing pulmonary nodules of malignant or fungal etiology in SOT recipients.


Dehydration in children with diabetic ketoacidosis: a prospective study.
To investigate the association between the degree of patient dehydration on presentation with diabetic ketoacidosis (DKA) and clinical and laboratory parameters obtained on admission. Prospective descriptive study. A tertiary care children's hospital. Thirty-nine paediatric patients (1 month-16 years) presenting with 42 episodes of DKA. Clinical and biochemical variables were collected on admission. Dehydration was calculated by measuring acute changes in body weight during the period of illness. All patients were treated according to a previously established protocol. Magnitude of dehydration, defined as % loss of body weight (LBW), was determined by the difference in body weight obtained at presentation and at discharge. The relationship between the magnitude of dehydration and the clinical assessment and biochemical parameters was examined. The median (25th-75th centiles) magnitude of dehydration at presentation was 5.7% (3.8-8.3%) (mean ± SD 6.8 ± 5%). Neither the initial clinical assessment nor the comprehensive biochemical profile at admission correlated with the magnitude of dehydration. Despite considerable variation in the degree of dehydration and biochemical disequilibrium, all patients recovered from DKA within 24 h with a standardised therapeutic approach. Furthermore, the rapidity of patient recovery did not correlate with the magnitude of dehydration on presentation or the amount of fluid administered (median (25th-75th centiles) 48.8 ml/kg (38.5-60.3)) in the first 12 h. The magnitude of dehydration in DKA is not reflected by either clinical or biochemical parameters. These findings need confirmation in larger studies.


Incidence and predictors of loss to follow-up among HIV infected adults after initiation of first line anti-retroviral therapy at University of Gondar comprehensive specialized Hospital Northwest Ethiopia, 2018: retrospective follow up study.
The aim of this study was to estimate the incidence of lost to follow up from anti-retroviral therapy (ART) care and identify the associated factors among human immunodeficiency virus (HIV) infected patients after first-line ART initiation at University of Gondar comprehensive specialized hospital, Northwest Ethiopia between January 2012 and January 2018. The overall incidence rate of lost to follow up was 12.26 per 100 person years (95% CI (10.61-14.18)). Being underweight (< 18.5 kg/m2) (AHR, 1.52, 95% CI 1.01-2.28), jobless (AHR, 2.22, 95% CI 1.2-4.11), substance abuser (AHR, 1.84 95% CI 1.19-2.86), having sub-optimal adherence (fair/poor) (AHR 6.33, 95% CI (3.90-10.26)), not receiving isoniazid prophylaxis (AHR 2.47, 95% CI (1.36-4.48)), ambulatory functional status (AHR 1.94, 95% CI (1.23-3.06)), having opportunistic infections (AHR, 1.74 95% CI 1.11-2.72), having CD4 count 201-349 cells/µL (AHR 0.58, 95% CI (0.38-0.88)) were found to be significant predictors of lost to follow up from ART service.


Case control study to investigate risk factors for bovine neonatal pancytopenia (BNP) in young calves in southern Germany.
A case control study on farm level was conducted at the Clinic for Ruminants, LMU Munich, to identify possible risk factors associated with the observed increase in numbers of calves showing clinical signs of Bovine Neonatal Pancytopenia (BNP) since 2006 in southern Germany. Interviews were conducted between August 2008 and June 2010. The characteristics of 56 dairy farms with at least one confirmed case of BNP (thrombocytopenia and leukocytopenia and/or typical findings in post-mortem examination and bone marrow histology) were compared with those of two sets of 50 control dairy farms each, with no history of BNP. The first set of 50 control farms was selected randomly from veterinary practices which had never observed a BNP case on the farms they serviced. The second set of 50 control farms was matched by the veterinary practices which had provided case farms. Two separate analyses were conducted: (1) case farms (n=56) vs. randomly selected control farms (n=50) and (2) case farms (n=56) vs. a matched set of control farms (n=50). All variables with p<0.2 in the univariable analysis were included in stepwise logistic regression models. In the first analysis, only the use of PregSure(®) BVD vaccine was positively associated with BNP with an odds ratio of 1292 (95% CI: 114-14707). In the second analysis, conditional logistic regression models did not converge, therefore non-conditional logistic regression models were conducted. In the non-conditional analysis five variables remained in the model, three of which were negatively associated with BNP: the use of vitamin E and selenium, the frequent use of mastitis tubes, and the use of stem growth regulators in grain production. The use of prophylactic measures (such as control of parasites or vaccination of calves against respiratory disease) was positively associated with BNP with an odds ratio of 14.3 as well as the use of PregSure(®) BVD vaccine with an odds ratio of 426 (95% CI: 20-9095).


Uptake of reactive textile dyes by Aspergillus foetidus.
An isolated fungus, Aspergillus foetidus was found to effectively decolorize media containing azo reactive dyes namely, Drimarene dyes. The extent of color removal was greater than 95% within 48 h of growth of the fungus. The entire color was found to be strongly bioadsorbed to the rapidly settling fungal biomass pellets without undergoing significant biotransformation. Our investigations reveal that the process of decolorization is concomitant with the exponential growth phase of the fungus and has requirement for a biodegradable substrate such as glucose. The fungus was also able to decolorize media containing mixture of dyes to an extent of 85% within 72 h of growth. Kinetic analyses of fungal decolorization indicate that the process is time dependent and follows first order kinetics with respect to initial concentration of dye. The rates of color uptake (k values) decrease to a significant extent with increasing initial concentrations of dye. The fungus was able to grow and decolorize media in the presence of 5 ppm of chromium and 1% sodium chloride. An alternate and cheaper carbon source such as starch supported the growth and decolorization process. These results suggest that dye uptake process mediated by A. foetidus has a potential for large-scale treatment of textile mill discharges.


TDDFT investigation on nucleic acid bases: comparison with experiments and standard approach.
A comprehensive theoretical study of electronic transitions of canonical nucleic acid bases, namely guanine, adenine, cytosine, uracil, and thymine, was performed. Ground state geometries were optimized at the MP2/6-311G(d,p) level. The nature of respective potential energy surfaces was determined using the harmonic vibrational frequency analysis. The MP2 optimized geometries were used to compute electronic vertical singlet transition energies at the time-dependent density functional theory (TDDFT) level using the B3LYP functional. The 6-311++G(d,p), 6-311(2+,2+)G(d,p), 6-311(3+,3+)G(df,pd), and 6-311(5+,5+)G(df,pd) basis sets were used for the transition energy calculations. Computed transition energies were found in good agreement with the corresponding experimental data. However, in higher transitions, the Rydberg contaminations were also obtained. The existence of pisigma* type Rydberg transition was found near the lowest singlet pipi* state of all bases, which may be responsible for the ultrafast deactivation process in nucleic acid bases.


Delayed discharges from a tertiary teaching hospital in Israel- incidence, implications, and solutions.
The Israeli health system is facing high workloads with average occupancy in certain hospital wards of around 100%. Since there is a shortage of hospitalization beds in institutions for continuous, long-term care, transferring patients from the general hospitals' wards is often delayed. This situation has many significant ramifications, to the waiting patients themselves, to other patients who are waiting to be treated and to the entire organization. In this study, we describe the phenomenon of the "detained patients" - its extent, characteristics, significance, and possible solutions. Rambam Health Care Campus is a tertiary medical center serving the population of the northern part of Israel. In recent years, the hospital management documents data regarding the "detained patients". We reviewed hospital data of detained patients over a period of nine months. The data concerning adult patients awaiting transfer to an institution for continuous care, between May 2019 and January 2020, were obtained retrospectively from the computerized database of the social service. During the study period, 12,723 adult patients were discharged. Of those, 857 patients (6.74%) were transferred to one of the facilities providing prolonged institutional care. For that group of patients, median inpatient waiting time from the decision to discharge until the transfer was 8 days (IQR 6-14), translating to 10,821 waiting days or 1202 hospitalization days per month. These hospitalization days account for 9.35% of the total hospitalization days during the study period. The "detained patients" were hospitalized in internal medicine wards (32%), orthopedic (30%), and neurology/neurosurgery (26%) departments. At any given moment, about 40 hospitalized patients were waiting for long-term care facilities. Health-care systems must adapt to the current patients' case-mix to achieve optimal utilization of hospital beds and maximal operational efficiency. The number of long-term care beds should be increased, the coordination between general hospitals, health maintenance organizations and long-term facilities improved, and patients that may require long term care after the acute phase of their illness should be early identified and addressed. Meanwhile, establishment of organic units for waiting patients and reorganization of the hospital structure should be considered.


Fast and slow dynamics of the cytoskeleton.
Material moduli of the cytoskeleton (CSK) influence a wide range of cell functions. There is substantial evidence from reconstituted F-actin gels that a regime exists in which the moduli scale with frequency with a universal exponent of 3/4. Such behaviour is entropic in origin and is attributable to fluctuations in semiflexible polymers driven by thermal forces, but it is not obvious a priori that such entropic effects are responsible for the elasticity of the CSK. Here we demonstrate the existence of such a regime in the living cell, but only at high frequencies. Fast events scaled with frequency in a manner comparable to semiflexible-polymer dynamics, but slow events scaled with a non-universal exponent that was systematically smaller than 3/4 and probably more consistent with a soft-glass regime. These findings strongly suggest that at smaller timescales elasticity arises from entropic fluctuations of a semiflexible-filament network, whereas on longer timescales slow (soft-glass-like) dynamics of a different origin prevail. The transition between these two regimes occurred on timescales of the order of 0.01 s, thus setting within the slow glassy regime cellular events such as spreading, crawling, contracting, and invading.


Activation of chloride conductance in pig jejunal brush border vesicles.
Requirements for the activation of Cl- conductance have been investigated in pig jejunal brush border vesicles. The stability of ATP as a substrate for protein kinase activity, the stability of the phosphoprotein product of protein kinase action, and the choice of buffer system used for vesicle preparation were studied as variables which affected the outcome of in vitro activation attempts. Arsenate was selected as the most effective agent in protecting ATP from hydrolysis by the phosphatase activity in this vesicle system. Brush border vesicle protein appeared to prevent the accumulation of phosphoprotein in a cAMP-dependent protein kinase reaction, and vesicle protein only had phosphate acceptor activity when KF was added as a presumptive inhibitor of phosphoprotein phosphatase. A Cl- conductance response to a potassium gradient and valinomycin was present in vesicles prepared in buffers containing tetramethylammonium. Cl- conductance activity was not increased in this system by the addition of ATP, dibutyryl cyclic AMP, and cyclic AMP-dependent protein kinase. There was no Cl conductance response to a potassium gradient in vesicles buffered with imidazolium-acetate. Incorporation of ATP, AsO4(3-), and F- into these nonconductive vesicles by homogenization, followed by addition of dibutyryl cAMP, produced substantial conductance activity. Maximal activation of Cl- conductance was obtained with vesicles prepared in imidazolium-acetate buffering, using precautions to stabilize ATP and phosphoprotein prior to conductance measurements.


Acquired haemophilia complicating the remission of a patient with high grade non-Hodgkin's lymphoma treated by fludarabine.
We report the development of a high titre antibody to factor VIII in a patient with previous high grade B cell non-Hodgkin's lymphoma treated with fludarabine. Unlike previous reports of factor VIII inhibitors and lymphoproliferative disease this patient's lymphoma was in remission. We speculate that the occurrence of the inhibitor is another manifestation of the increasingly recognized autoimmune side-effects of fludarabine.


[Difference in the capacity to repair DNA damage in human cells chronically infected with the rubella virus].
Centrifugation of cell lysates in alkaline sucrose gradients and chromatography on hydroxyapatite columns were used to demonstrate inhibition of reparation of mitomycin C-induced DNA damages at the stage of reunification of single-strand breaks of DNA in human HEp-2 cell cultures chronically infected with rubella virus. At the same time, reparation of single-strand breaks of DNA caused by bleomycin occurs with similar intensity both in chronically infected and noninfected HEp-2 cultures. The experimental results suggest that the chronic course of infection in human cells leads to disorders in reparative synthesis of cellular DNA and/or is due to disconnected effect of reparation enzymes in this system.


Effect of an increased intraperitoneal pressure on fluid and solute transport during CAPD.
The effect of an increased intraperitoneal pressure on fluid and solute transport was studied in eight stable CAPD patients. Two permeability tests of two hours each with continuous registration of the intraperitoneal pressure were performed while patients were in supine position. The intra-abdominal pressure was raised by means of a tightening girdle with inflatable cuffs in one of the experiments. Intraperitoneally administered dextran 70 was used as a volume marker in order to determine the peritoneal fluid kinetics. The increment in the intra-abdominal pressure of 10.0 +/- 1.0 mm Hg caused a decline in the net ultrafiltration. This was mainly determined by an increase in the lymphatic absorption: 1.07 +/- 0.18 ml/min (without compression) versus 1.86 +/- 0.25 ml/min (with compression; P < 0.01), whereas the transcapillary ultrafiltration rate tended to decrease: 2.02 +/- 0.23 versus 1.73 +/- 0.27 ml/min (P = 0.08). External compression also diminished solute transport from the circulation to the peritoneal cavity. The decline in the mass transfer area coefficient of urea, creatinine, urate and beta 2-microglobulin was 13%, indicating a smaller effective peritoneal surface area caused by external compression probably due to a decrease in the number of the perfused peritoneal capillaries. The fall in the peritoneal protein clearances was more pronounced the higher the molecular weight of the protein, consistent with a decline in the intrinsic permeability of the peritoneum. Kinetic modeling using computer simulations was used to analyse these effects in terms of the pore theory, using a convection model (large pore radius 184 +/- 14 A) and a diffusion model (large pore radius 1028 +/- 218 A) for the transport of macromolecules.(ABSTRACT TRUNCATED AT 250 WORDS)


Diagnostic value of transrectal combined scrotal ultrasonography in acquired obstructive azoospermia.
To investigate the transrectal and scrotal ultrasonographic features of acquired obstructive azoospermia and evaluate the role of ultrasonography in the location diagnosis of acquired obstructive azoospermia patients. Retrospectively analysis of 92 cases of acquired obstructive azoospermia in recent years. All the patients underwent transrectal and scrotal ultrasonography. The ultrasonographic features were observed of testis, epididymis, scrotal segment of vas deferens, seminal vesicle, ejaculatory duct and prostate. Eighty cases with normal semen were taken as control group. Among the 92 cases of acquired obstructive azoospermia, 28 cases were prostate midline cyst, 32 cases were stone or calcification of the ejaculation duct and 21 cases were chronic seminal vesicle inflammation, which were found through transrectal ultrasonography; 27 cases were vas deferens dilation, 30 cases had abnormal mass of epididymis tail, 31 cases were epididymis thickness with reticular change, 8 cases were cystic dilatation of rete testis, which were found through scrotal ultrasonography. Compared with the control group, ultrasound examination increased the detection rate of distal seminal duct lesions and epididymal lesions in acquired obstructive azoospermia patients (p<.01). Comparison of testicular volume between case group and control group did not reveal significant difference (p>.05). The thickness of the head, body and tail of epididymis in case group was significantly bigger than that in control group (p<.01). Transrectal and scrotal ultrasonography can find lesions in different parts of the seminal passage. Acquired obstructive azoospermia patients have increased rate of distal seminal duct lesions, epididymal lesions and epididymis volume. Transrectal and scrotum ultrasonography can provide reliable imaging evidence for the location diagnosis of acquired obstructive azoospermia.


Can cell therapy heal a spinal cord injury?
Literature survey. To summarize and discuss current possibilities and success rates for the treatment of spinal cord injury in animal models. University of Antwerp, Belgium. We searched Pubmed for publications from 1997 onwards. Seven older papers were used for completion of data. Despite major progress in pharmacological and surgical approaches, a spinal cord injury still remains a very complex medical and psychological challenge, both for the patients and their relatives, as well as for the involved physicians, with currently no existing curative therapy. For a future efficient treatment, one has to consider and combine four main approaches: (1) tissue or cell transplantation, (2) providing growth-stimulating factors (neurotrophic factors), (3) blocking factors which inhibit neural regeneration and (4) modulation of inflammatory response following spinal cord injury. Although different treatment options have proven to be successful in animal models, they also provide a realistic view on a complex therapeutical approach, which needs to be further investigated in many carefully designed animal studies before human applications can be considered.


Epidemiological Features of Cardiovascular Disease in Asia.
Cardiovascular disease (CVD) is the leading cause of death in Asia. To combat the harmful impacts of CVD on public health in Asian countries with more effective strategies and actions, it is crucial to understand the current epidemiologic features of CVD in Asia. Through a systematic study and analysis of various timely data on CVD epidemiology in Asian countries from multiple sources, this state-of-the-art review provides an overview of the important epidemiologic features of CVD in Asia. Current and future challenges in CVD prevention implied by the epidemiologic features in Asian countries are highlighted and discussed in this review.


Evaluating the case-positive, control test-negative study design for influenza vaccine effectiveness for the frailty bias.
Previous influenza vaccine effectiveness studies were criticized for their failure to control for frailty. This study was designed to see if the test-negative study design overcomes this bias. Adults ≥ 50 years of age with respiratory symptoms were enrolled from November 2006 through May 2012 during the influenza season (excluding the 2009-2010 H1N1 pandemic season) to perform yearly test-negative control influenza vaccine effectiveness studies in Nashville, TN. At enrollment, both a nasal and throat swab sample were obtained and tested for influenza by RT-PCR. Frailty was calculated using a modified Rockwood Index that included 60 variables ascertained in a retrospective chart review giving a score of 0 to 1. Subjects were divided into three strata: non frail (≤ 0.08), pre-frail (> 0.08 to < 0.25), and frail (≥ 0.25). Vaccine effectiveness was calculated using the formula [1-adjusted odds ratio (OR)] × 100%. Adjusted ORs for individual years and all years combined were estimated by penalized multivariable logistic regression. Of 1023 hospitalized adults enrolled, 866 (84.7%) participants had complete immunization status, molecular influenza testing and covariates to calculate frailty. There were 83 influenza-positive cases and 783 test-negative controls overall, who were 74% white, 25% black, and 59% female. The median frailty index was 0.167 (Interquartile: 0.117, 0.267). The frailty index was 0.167 (0.100, 0.233) for the influenza positive cases compared to 0.183 (0.133, 0.267) for influenza negative controls (p = 0.07). Vaccine effectiveness estimates were 55.2% (95%CI: 30.5, 74.2), 60.4% (95%CI: 29.5, 74.4), and 54.3% (95%CI: 28.8, 74.0) without the frailty variable, including frailty as a continuous variable, and including frailty as a categorical variable, respectively. Using the case positive test negative study design to assess vaccine effectiveness, our measure of frailty was not a significant confounder as inclusion of this measure did not significantly change vaccine effectiveness estimates.


Guidelines for the management of hyperlipidemia: How can clinicians effectively implement them?
Guidelines support lowering cholesterol to decrease atherosclerotic cardiovascular disease (ASCVD) risk across the entire lifespan with intensive lifestyle intervention, as well as statin and non-statin pharmacotherapy for those at highest risk. Modest improvements in the initiation, use, and adherence to statin therapy in patients with ASCVD have occurred over the past decades. However, studies continue to document a less than desired implementation of guidelines highlighting a substantial and persistent treatment gap. The success of implementation depends on the consideration of a variety of barriers that exist throughout the healthcare delivery system. Further research is needed to comprehensively evaluate these barriers in order to develop appropriate and sustainable interventions to improve guideline implementation.


Altered gut microbiota in older adults with mild cognitive impairment: a case-control study.
The microbiota-gut-brain axis is implicated in Alzheimer's disease. Gut microbiota alterations in mild cognitive impairment (MCI) are inconsistent and remain to be understood. This study aims to investigate the gut microbial composition associated with MCI, cognitive functions, and structural brain differences. A nested case-control study was conducted in a community-based prospective cohort where detailed cognitive functions and structural brain images were collected. Thirty-one individuals with MCI were matched to sixty-five cognitively normal controls by age strata, gender, and urban/rural area. Fecal samples were examined using 16S ribosomal RNA (rRNA) V3-V4 sequencing. Compositional differences between the two groups were identified and correlated with the cognitive functions and volumes/thickness of brain structures. There was no significant difference in alpha and beta diversity between MCIs and cognitively normal older adults. However, the abundance of the genus Ruminococcus, Butyricimonas, and Oxalobacter decreased in MCI patients, while an increased abundance of nine other genera, such as Flavonifractor, were found in MCIs. Altered genera discriminated MCI patients well from controls (AUC = 84.0%) and were associated with attention and executive function. This study provides insights into the role of gut microbiota in the neurodegenerative process.


Fractional ablative carbon dioxide laser treatment of facial scars: Improvement of patients' quality of life, scar quality, and cosmesis.
Disfiguring facial scars can be a massive burden on patients' psychosocial health and severely impact patients' self-esteem. The aim of this study was to analyze whether ablative fractional carbon dioxide laser (CO2-AFL) treatment can positively influence facial scarring and quality of life (QoL) while improving the aesthetic appearance. Patients with facial scars who had received CO2-AFL treatment between May 2019 and May 2020 were included in a retrospective study. The post-interventional course and patient and/or observer reported outcomes were inquired before and three months after treatment. Primary outcomes were changes in the Patient and Observer Scar Scale (POSAS) and QoL (Short Form (SF) 36). In addition, two independent examiners evaluated the aesthetic outcome by comparing initial scarring with the post-intervention results using photographs. A total of 16 patients with facial scars were included. Most of the scars were caused by burns (43.8%) or trauma (31.3%). The post-interventional course was uneventful. Overall POSAS scores improved decisively for both observers (n=2) and patients (n=16) (p<0.001 and p<0.001). Also, there was an improvement in QoL with an increase in emotional well-being (p=0.043) and social functioning (p=0.01). Furthermore, the aesthetic outcome was significantly enhanced (p=0.001) after treatment. The CO2-AFL offers a safe and effective treatment for disfiguring facial scars. We have shown that improvement of scar appearance and scar quality was meaningful to the patient, with a significant impact on a patient's life quality. Based on these findings we suggest including the CO2-AFL in the facial scar treatment concept.


Robot-Automated Cartilage Contouring for Complex Ear Reconstruction: A Cadaveric Study.
Auricular reconstruction requiring manual contouring of costal cartilage is complex and time consuming, which could be facilitated by a robot in a fast and precise manner. This feasibility study evaluates the accuracy and speed of robotic contouring of cadaver costal cartilage. An augmented robot with a spherical burr was used on cadaveric rib cartilage. Using a laser scanner, each rib section was converted to a three-dimensional model for preoperative planning. A model ear was also scanned to define a carving path for each piece of cartilage. After being contoured, each specimen was compared against the preoperative plan utilizing deviation maps to analyze topographic accuracy. Contouring times of the robot were compared with 13 retrospectively reviewed cases (2006-2017) by an experienced surgeon. Scanning the cartilage sections took 24.8 ± 6.8 seconds. Preoperative processing took an additional 29.9 ± 8.9 seconds for the preparation of the contouring path. Once the path was prepared, the robot contoured the specimens with a root mean square error of 0.54 mm and a mean absolute deviation of 0.40 mm. The average time to contour the specimens with the robot was 13 ± 2 minutes compared to 71 ± 6 minutes for the manual contouring in the reviewed cases. The accuracy of the robotic system was high, with submillimeter deviations from the preoperative plan. The robot required <20% of the contouring time compared to the experienced surgeon. This represents a fast and accurate alternative to hand-contouring costal cartilage grafts for auricular reconstruction. Laryngoscope, 131:1002-1007, 2021.


Proteolytic degradation of protein kinase C in the phorbol ester-induced interleukin-2 secreting thymoma cells.
Effects of phorbol 12-myristate 13-acetate (PMA) on the fate of protein kinase C in two mouse thymoma cell lines, which are either responsive (EL4) or unresponsive (IEL4) to PMA-induced interleukin-2 (IL-2) production, were investigated with polyclonal antibodies raised against rat brain enzyme. These antibodies immunoprecipitated completely the protein kinase C from both cell lines and detected mainly an 82-kDa protein by immunoblot analysis of the crude homogenates as well as the partially purified kinase preparations. PMA elicited a time- and dose-dependent redistribution of protein kinase C from cytosol to the particulate fraction and proteolytic degradation of the kinase from both cell lines. The dose of PMA required for half-maximum protein kinase C translocation and degradation was at least five times lower for EL4 than for IEL4. In the presence of 16 nM PMA the rates of protein kinase C translocation and degradation were faster in EL4 than in IEL4, and the half-lives of protein kinase C in EL4 and IEL4 were less than 5 min and greater than 2 h, respectively. Analysis of the tryptic fragments of the immunoprecipitated enzyme, previously phosphorylated in the presence of [gamma-32P]ATP, revealed minor structural differences between the protein kinase C from these two cell lines. In neither cell line did the PMA-induced degradation of protein kinase C result in an accumulation of the Ca2+/phospholipid-independent kinase (catalytic unit) as analyzed by immunoblotting and gel filtration chromatography. Thus, activation of protein kinase C through the proteolytic conversion to the effector-independent catalytic unit plays little role in IL-2 production. The role of protein kinase C translocation and degradation in the PMA-induced responses in EL4 cells is unknown. However, IL-2 production in EL4 cells was reduced when PMA-induced degradation of protein kinase C was retarded by exogenously added protease inhibitors.


Improvement of photosynthesis in zooxanthellate corals by autofluorescent chromatophores.
Autofluorescent chromatophores were detected in 17 out of 71 zooxanthellate coral species studied. Chromatophores are localized either in the oral gastrodermic (endoderm) or oral epidermis (ectoderm). The pigment granules within the chromatophores (0.5-1.0 μm in diameter) show a brilliant light-blue/turquoise autofluorescence (emission between 430 and 500 nm) after excitation with light of 365-410 nm. All species where the autofluorescent gastrodermal chromatophores form a compact layer, embedding the zooxanthellae, belong to the family Agariciidae. In contrast, some species of the Faviidae (2), Pectiniidae (1) and Mussidae (1) were found to have distinct, autofluorescent chromatophores in the oral epidermis. Autofluorescent pigments of the host may enhance photosynthesis of the symbionts as in Leptoseris fragilis. Short wavelength irradiance, less suitable for photosynthesis, is transformed by host pigments into longer wavelengths which are photosynthetically more effective. Thus, host species possessing autofluorescent chromatophores might have selective advantage over non-fluorescent species, and have the potential to survive in light-limited habitats. Furthermore, the daily period of photosynthesis is extended, thus increasing the energy supply and enhancing the deposition of skeletal carbonate. The absence or presence of chromatophores may have value in taxonomy and could putatively be of plalaeontological and palaeoecological interest.


Stability of the Iceberg Profile as a function of perceived difficulty in defeating an opponent.
9 starters and 8 nonstarters of a university women's softball team completed the Profile of Mood States prior to playing the team perceived to be the most and least difficult to defeat in their conference. A significant interaction indicated that nonstarters displayed higher fatigue prior to playing the opponent perceived as most difficult to defeat. In addition, significant mean differences were found between starters and nonstarters on constructs of Anger, Confusion, Tension, and Depression, suggesting that nonstarters may not share same psychological profile as their peers who start.


The comparison in reduction of QT dispersion after primary percutaneous coronary intervention according to existence of thrombectomy in ST-segment elevation myocardial infarction.
Primary percutaneous coronary intervention (PPCI) is the standard treatment in patients with ST-segment elevation myocardial infarction (STEMI). Thrombectomy devices are used to remove thrombus or to prevent embolization of thrombus and plaque during PPCI. QT dispersion (the difference between maximal and minimal QT interval calculated on a standard 12-lead electrocardiogram) represents the regional nonuniformity of ventricular repolarization. It may reflect early coronary reperfusion in reducing electrophysiological instability by decreasing QT dispersion in the recovery phase after acute STEMI. Our aim was to show whether an additional effect of thrombectomy on reducing QT dispersion will be seen in patients undergoing PPCI for STEMI. The study population included 80 consecutive patients who were admitted to the hospital within 12 hours after the onset of acute STEMI and angiographic evidence of intraluminal thrombus in the infarct-related artery. Patients with atrial fibrillation or flutter, intraventricular conduction abnormalities, pre-excitation, cardiogenic shock, cardiomyopathy, ventricular hypertrophy, and severe valvular heart disease were excluded from the study. There were no significant differences between groups regarding gender, age, cardiovascular risk factors, and time from symptom onset to treatment, except for smoking, which was much higher in the PPCI plus thrombectomy group. Infarct-related artery distribution (left anterior descending artery [LAD] to non-LAD), and neither the rate of balloon predilatation nor stent implantation were different between groups. Successful coronary patency was achieved in each case. QT interval measurements were similar between groups at admission. However, at 24 hours, QT and QTc dispersions were less in the PPCI plus thrombectomy group (41 ± 9 vs 33 ± 7 ms, P < 0.05 and 45 ± 8 vs 35 ± 7 ms, P = 0.03, respectively), but not in the other QT interval measurements. When patients were divided into 2 groups according to infarct-related artery (LAD and non-LAD groups), QT interval measurement parameters did not show any significant differences. Thrombectomy additional to PPCI helps more effective reperfusion at the microvascular level and provides additional prognostic information.