Computer-Guided Surgery Using Human Allogenic Bone Ring With Simultaneous Implant Placement: A Case Report.
The allogenic bone ring technique allows for horizontal and vertical bone augmentation with simultaneous implant placement in severely compromised sites. The aim of this report is to present a modified protocol for simultaneous placement of implant and allogenic bone ring graft using a computer-guided surgery technique. Patient's chief complaint was to replace a missing lateral incisor. The implant site presented both vertical and horizontal tissue deficiencies. Study models and wax-ups were digitally scanned to stl files and merged with the existing CBCT data in the implant planning software. A 3D representation of an allogenic bone ring was developed, and two digitally designed guides were created: a 5 mm sleeve guide for the implant site and a 7 mm sleeve guide for the allogenic bone ring trephine. Both the implant site and the allogenic bone ring recipient site were prepared using the computer-generated guides. Once the ring was adapted into the recipient site, the implant was inserted through the allogenic bone ring. The healing was monitored and the implant was restored at 12 months. The accuracy of implant placement was measured and the difference in the final positioning was as follows: 0.6 mm at entry point, 0.55 mm vertical displacement, 1.94 mm at the apex, and angle discrepancy 6.1°. The use of computer-guided technology for planning and placement of an allograft bone block with simultaneous implant insertion allows for a prosthetically driven team approach to compromised site grafting in addition to improving precision and accuracy when compared with non-guided techniques.


Causes and risk factors of an unplanned second craniotomy in patients with traumatic brain injury.
The purpose of this retrospective study was to evaluate the causes and risk factors of an unplanned second craniotomy in patients with traumatic brain injury (TBI). A total of 219 patients with TBI who underwent initial unilateral intracranial supratentorial surgery between January 2016 to November 2021 were included. We evaluated the causes of an unplanned second craniotomy in 40 patients, and analyzed the risk factors for a contralateral second craniotomy in 21 patients using a multivariate logistic regression analysis. The most common cause for an unplanned second craniotomy was delayed or enlarged hematoma in the non-operation area (26/40; 65%), followed by recurrent hematoma in the operation area (8/40; 20%), ipsilateral massive cerebral infarction (3/40; 7.5%), diffuse brain swelling (2/40; 5%) and enlarged cerebral contusion (1/40; 2.5%). Multivariate logistic regression analysis showed that a contralateral craniocerebral injury feature (CCIF) (OR = 13.175), defined on preoperative computerized tomography scanning, was independent risk factor for a contralateral second craniotomy. An unplanned second craniotomy in patients with TBI was mainly related to delayed or enlarged hematoma. An increased risk of a contralateral second craniotomy occurs in patients with CCIF.


Programmed cell death in aortic aneurysm and dissection: A potential therapeutic target.
Rupture of aortic aneurysm and dissection (AAD) remains a leading cause of death. Progressive smooth muscle cell (SMC) loss is a crucial feature of AAD that contributes to aortic dysfunction and degeneration, leading to aortic aneurysm, dissection, and, ultimately, rupture. Understanding the molecular mechanisms of SMC loss and identifying pathways that promote SMC death in AAD are critical for developing an effective pharmacologic therapy to prevent aortic destruction and disease progression. Cell death is controlled by programmed cell death pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis. Although these pathways share common stimuli and triggers, each type of programmed cell death has unique features and activation pathways. A growing body of evidence supports a critical role for programmed cell death in the pathogenesis of AAD, and inhibitors of various types of programmed cell death represent a promising therapeutic strategy. This review discusses the different types of programmed cell death pathways and their features, induction, contributions to AAD development, and therapeutic potential. We also highlight the clinical significance of programmed cell death for further studies.


The incidence of atrial fibrillation and the added value of thumb ECG for detecting new cases.
To evaluate the incidence of atrial fibrillation (AF) as well as the value of thumb electrocardiography (ECG) for identification of paroxysmal AF in a Swedish cohort of middle-aged men from the general population. A population based random cohort of 798 men underwent screening at the age of 50 and re-examined at the age of 60 and 71 years. At the last examination, a thumb ECG recording was conducted for 2 weeks twice a day in 479 men from the original cohort. Registered hospital AF diagnoses were retrieved from the Swedish Patient Registry from 1993 to 2014. During a 21-year follow-up, 77 men (9.6%) were diagnosed with AF; of these men, 49.4% (38 of 77) had permanent AF. Fifteen of 479 (3.1%) patients had paroxysmal AF. Of those, seven had been previously diagnosed with paroxysmal AF through Patient Registry. The incidence of AF increased from 2.2 per 1000 years at risk at the age of 50-54 years to 9.3 per 1000 years at risk at the age 65-70 years. The prevalence of AF at the age of 71 years was increased from 7.1% to 9.9% using thumb ECG. In addition to medical history, patient register and 12-lead -ECG, the use of thumb ECG increased the number of detected paroxysmal AF by 21%.


Optimized analysis parameters of variant calling for whole genome-based phylogeny of Mycobacteroides abscessus.
Whole-genome sequence (WGS) analysis provides the best resolution for reconstructing bacterial phylogeny. However, the resulting tree could vary according to parameters used in the WGS pipeline, making it difficult to compare results across multiple studies. This study compares effects on phylogenies when applying different parameter stringencies. We used as the study model to optimize parameters strains of Mycobacteroides abscessus serially isolated at various intervals, isolates known to represent persistent infection (PI) cases or re-infection (RI) cases and isolates from different subspecies. Un-optimized parameters with low stringency provided an excessive number of SNPs (823) compared to the optimized setting (3 SNPs) between paired strains isolated 1 day apart from PI cases, discordant tree topology and misclassification of subspecies and of instances of RI. We demonstrated that using high-quality variants provides more accuracy for recognizing serial isolates of the same clone versus different clones and for phylogenetic analysis of M. abscessus. Our approach might be used as a model for analyses requiring phylogenetic reconstruction of other bacteria.


Transforming growth factor-beta 1 increases bad phosphorylation and protects neurons against damage.
Despite the characterization of neuroprotection by transforming growth factor-beta1 (TGF-beta1), the signaling pathway mediating its protective effect is unclear. Bad is a proapoptotic member of the Bcl-2 family and is inactivated on phosphorylation via mitogen-activated protein kinase (MAPK). This study attempted to address whether MAPK signaling and Bad phosphorylation were influenced by TGF-beta1 and, furthermore, whether these two events were involved in the antiapoptotic effect of TGF-beta1. We found a gradual activation of extracellular signal-regulated kinase 1/2 (Erk1/2) and MAPK-activated protein kinase-1 (also called Rsk1) and a concomitant increase in Bad phosphorylation at Ser(112) in mouse brains after adenovirus-mediated TGF-beta1 transduction under nonischemic and ischemic conditions induced by transient middle cerebral artery occlusion. Consistent with these effects, the ischemia-induced increase in Bad protein level and caspase-3 activation were suppressed in TGF-beta1-transduced brain. Consequently, DNA fragmentation, ischemic lesions, and neurological deficiency were significantly reduced. In cultured rat hippocampal cells, TGF-beta1 inhibited the increase in Bad expression caused by staurosporine. TGF-beta1 concentration- and time-dependently activated Erk1/2 and Rsk1 accompanied by an increase in Bad phosphorylation. These effects were blocked by U0126, a mitogen-activated protein kinase/Erk kinase 1/2 inhibitor, suggesting an association between Bad phosphorylation and MAPK activation. Notably, U0126 and a Rsk1 inhibitor (Ro318220) abolished the neuroprotective activity of TGF-beta1 in staurosporine-induced apoptosis, indicating that activation of MAPK is necessary for the antiapoptotic effect of TGF-beta1 in cultured hippocampal cells. Together, we demonstrate that TGF-beta1 suppresses Bad expression under lesion conditions, increases Bad phosphorylation, and activates the MAPK/Erk pathway, which may contribute to its neuroprotective activity.


Use of serum CA 125 measurement in posttreatment surveillance of early-stage endometrial carcinoma.
Serum CA 125 levels were normal preoperatively in 123 of 125 (98.4%) patients with clinical and surgical stage I or II endometrial adenocarcinoma, and remained so in all patients who remained without evidence of either isolated vaginal recurrence or postoperative radiation enteritis. Recurrent disease developed in 13 patients. All of those who had pelvic (1), abdominal (4), or pulmonary (2) metastases had elevated serum CA 125 levels. None of the six patients with isolated vaginal recurrences had elevated CA 125 levels. Four patients had small bowel obstruction as a result of postoperative pelvic radiation, and all had elevated CA 125 levels during these episodes, although no evidence of recurrent disease was found during exploratory laparotomy for intestinal bypass. Serum CA 125 levels may have a role in the posttreatment surveillance of patients with early-stage endometrial carcinoma, but may be falsely elevated in the presence of severe radiation injury and at a normal level in the presence of isolated vaginal metastases.


[Radiographic analysis of limb malalignment in the frontal plane].
Radiographic measurement of the lower limb alignment in the frontal plane is used to assess limb deformity, to plan corrective surgery and for follow-up. It is essential that age-related normal lower limb alignment and joint orientation angles are known before planning surgical treatment. EOS (EOS™ Imaging, Paris, France) can lead to supplemental information, especially in cases of severe multidimensional joint malalignment. It allows 3D reconstruction of a bone model of the limb to assess multi-dimensional deformity.


Ac154 carried out anti-apoptotic role during AcMNPV infection process in the host insect cells.
AcMNPV is the first baculovirus to be sequenced and is considered a model of baculovirus. ac154 is a later expression gene in AcMNPV genome and its function is unknown. In this study, we explored the function of Ac154 in AcMNPV infection process in host Sf9 cells. The results showed that Ac154 was distributed in both nucleus and cytoplasm. Knockout of ac154 did not affect the production of BV, but the yield of progeny virus was reduced, indicating the auxiliary function of Ac154 in virus production. MTT assay showed that Ac154 promoted the proliferation and inhibited apoptosis of Sf9 cells. Overexpression of ac154 gene significantly increased the transcription level of anti-apoptotic gene p35, and delayed the expression of the pro-apoptotic protein SfP53 and reduced its expression level, which indicated its anti-apoptotic role in the host cells. In conclusion, our results demonstrated Ac154 could delay apoptosis process in host cells by regulating the transcription of p35 gene and the expression of SfP53 protein, which provided a more favorable environment for progeny virus replication and packaging, thereby promoting the proliferation of progeny virus. So we provided a potentially improved bac-to-bac eukaryotic protein expression system and biopesticide in this work.


Prefrontal substrates of empathy: psychometric evidence in a community sample.
Empathy is a vicarious experience of others' emotions, and is crucial to many forms of adaptive social interaction. Clinical, experimental, and functional neuroimaging studies convergently suggest a role for prefrontal-limbic circuits in mediating empathy. This study examined the prefrontal basis of empathy in a community sample using self-report measures: the frontal systems behavior scale (FrSBe), Barratt impulsiveness scale (BIS), and the interpersonal reactivity index (IRI). Multiple correlations emerged supporting an inverse relationship between prefrontal system dysfunction and empathy, particularly emotional empathy and perspective taking. Many of these relationships persisted after controlling for age, sex, and education. However, FrSBe scales did not correlate with one's identification with fictional characters, and motor impulsivity correlated positively, presumably due to the different cognitive and emotional context (i.e. real versus fictional individuals). These studies parallel others using objective methodologies and suggest a graded relationship between prefrontal function and empathy and likely reflect normal variations in prefrontal-limbic function.


Neovascularization derived from cell transplantation in ischemic myocardium.
Myocardial ischemia triggers a limited angiogenic response, part of the remodeling process that is insufficient to avoid further functional impairment. Several strategies have been evaluated to regenerate myocardial vascularization after ischemic injury such as transmyocardial laser revascularization and gene therapy. Attention has recently been focused on the potential of cell therapy to induce angiogenesis. Enhancing myocardial neovascularization is a major goal of myocardial cell transplantation because it would provide patients, who cannot undergo conventional revascularization, with an alternative therapy. Additionally, neovascularization would provide the implanted cells with adequate microenvironment to enhance survival and function. This short review gives an overview of the effect of various cell transplantation strategies on myocardial neovascularization. It suggests that in order to optimize myocardial neovascularization induced by cell therapy, future experiments should focus on the contribution of exogenous and endogenous stem cells to new vessels formation, and on the identification of the molecular pathways involved in the process.


Establishment of caprine airway epithelial cells grown in an air-liquid interface system to study caprine respiratory viruses and bacteria.
Respiratory diseases negatively impact the global goat industry, but are understudied. There is a shortage of established and biological relevant in vitro or ex vivo assays to study caprine respiratory infections. Here, we describe the establishment of an in vitro system based on well-differentiated caprine airway epithelial cell (AEC) cultures grown under air liquid interface conditions as an experimental platform to study caprine respiratory pathogens. The functional differentiation of the AEC cultures was monitored and confirmed by light and immunofluorescence microscopy, scanning electron microscopy and examination of histological sections. We validated the functionality of the platform by studying Influenza D Virus (IDV) infection and Mycoplasma mycoides subsp. capri (Mmc) colonization over 5 days, including monitoring of infectious agents by titration and qPCR as well as colour changing units, respectively. The inoculation of caprine AEC cultures with IDV showed that efficient viral replication takes place, and revealed that IDV has a marked cell tropism for ciliated cells. Furthermore, AEC cultures were successfully infected with Mmc using a multiplicity of infection of 0.1 and colonization was monitored over several days. Altogether, these results demonstrate that our newly-established caprine AEC cultures can be used to investigate host-pathogen interactions of caprine respiratory pathogens.


Activity of cells in the lateral vestibular nucleus as a function of head position.
1. The spike activity of cells in the lateral vestibular nucleus was recorded in cats anaesthetized with pentobarbital sodium. Natural labyrinthine stimulation was applied by fixing the animal at different positions reached through roations about a longitudinal or transverse axis.2. The majority of cells responded to rotations only about the longitudinal axis. Two types of response were found. The first was characterized by a transient change in activity which occurred only during the movement. The second type had an initial transient component and a subsequent steady component that persisted as long as the head remained fixed.3. The interspike interval means, standard deviations, histograms and autocorrelograms of the steady response components of cells sensitive to lateral tilt were calculated. In every cell the relation between the head position with respect to gravity and the mean interspike interval of the steady discharge showed two main features. (a) ;Directional sensitivity': the mean interval increased following rotation in one sense, and decreased following rotation in the other. In twenty-two out of thirty-three cells, the mean increased when the recording side was raised. The remaining cells showed the opposite relation. (b) ;Multivaluedness': each particular position is associated with several different values of mean interval and these values had a relatively wide scatter. The curve that resulted from joining points in the order in which they occurred during the experiment was either closed, open, or combined closed and open portions.4. The standard deviations, histograms and autocorrelograms also showed directional sensitivity and multivaluedness with respect to position. Several types of interspike interval histograms and autocorrelograms characterized lateral vestibular activity. The forms of the histogram and the autocorrelogram of the discharge from each cell usually remained unchanged during stimulation.5. The extensive spread of the multivaluedness implies that observation of the mean interspike interval of a specified cell can lead only to a probabilistic statement about head position. Joint observations of mean, standard deviation and histogram, or joint observation of several cells or knowledge of the previous history of the movement may lead to a more accurate determination of position.6. Experiments in animals with only one labyrinth showed that each labyrinth can both accelerate and decelerate activity in both vestibular nuclei.


Analgesic Efficacy, Practicality and Safety of Inhaled Methoxyflurane Versus Standard Analgesic Treatment for Acute Trauma Pain in the Emergency Setting: A Randomised, Open-Label, Active-Controlled, Multicentre Trial in Italy (MEDITA).
Inhaled low-dose methoxyflurane is approved in Europe for emergency relief of moderate-to-severe trauma-related pain in adults, but data versus active comparators are sparse. The phase IIIb Methoxyflurane in Emergency Department in ITAly (MEDITA) trial investigated the analgesic efficacy, practicality and safety of methoxyflurane versus standard analgesic treatment (SAT) for acute trauma pain. This was a randomised, active-controlled, parallel-group, open-label trial conducted in 15 Italian emergency units. Adults with limb trauma and pain score ≥ 4 on numerical rating scale (NRS) were randomised 1:1 to inhaled methoxyflurane 3 mL or SAT [intravenously administered (IV) morphine 0.1 mg/kg for severe pain (NRS ≥ 7); IV paracetamol 1 g or IV ketoprofen 100 mg for moderate pain (NRS 4-6)]. The primary endpoint was overall change in visual analogue scale (VAS) pain intensity from baseline (time of randomisation) to 3, 5 and 10 min. Non-inferiority and superiority of methoxyflurane versus SAT were concluded if the upper 95% confidence interval (CI) for the treatment comparison (methoxyflurane-SAT) was less than 1 and less than 0, respectively. Between 8 February 2018 and 8 February 2019, 272 patients were randomised (136 per treatment group). A total of 270 patients (mean age 51 years; 49% male; 34% with severe pain; mean baseline VAS 67 mm) were treated and analysed for efficacy and safety. Superiority of methoxyflurane was demonstrated for moderate-to-severe pain (adjusted mean treatment difference - 5.94 mm; 95% CI - 8.83, - 3.06 mm), moderate pain (- 5.97 mm; 95% CI - 9.55, - 2.39 mm) and severe pain (- 5.54 mm; 95% CI - 10.49, - 0.59 mm). Median onset of pain relief was 9 min for methoxyflurane and 15 min for SAT. Practicality of methoxyflurane treatment was rated "Excellent", "Very Good" or "Good" by 90% of clinicians vs. 64% for SAT. Adverse events (all non-serious) were reported by 17% of methoxyflurane-treated patients and 3% of SAT-treated patients. Methoxyflurane provided superior pain relief to SAT in patients with moderate-to-severe trauma pain and may offer a simple, fast, effective non-opioid treatment option. Trial registered with EudraCT (2017-001565-25) on 2 March 2018 and ClinicalTrials.gov (NCT03585374) on 13 July 2018. Mundipharma Pharmaceuticals S.r.l.


Effect of pro-inflammatory cytokines on the toxicity of the arylhydroxylamine metabolites of sulphamethoxazole and dapsone in normal human keratinocytes.
Sulphonamides, such as sulphamethoxazole (SMX) and the related sulphone dapsone (DDS), show a higher incidence of cutaneous drug reactions (CDRs) in patients with the acquired immunodeficiency syndrome (AIDS) compared with human immunodeficiency virus (HIV) negative patients. During HIV infection, pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are increased. We hypothesized that this increase in pro-inflammatory cytokines may increase the toxicity of the arylhydroxylamine metabolites of SMX (S-NOH) and DDS (D-NOH) in keratinocytes through a reduction in glutathione (GSH) content. We evaluated the effect of TNF-alpha on GSH levels in normal human epidermal keratinocytes (NHEK) and found a significant decrease in GSH after 24h. Pre-treatment with TNF-alpha also resulted in an increase in the recovery of D-NOH, but failed to alter drug-protein covalent adduct formation in NHEK. We also evaluated the effect of TNF-alpha, IL-1 beta, interferon-gamma (IFN-gamma), lipopolysaccharide (LPS) and conditioned media (obtained from monocytes stimulated with LPS) on the cytotoxicity of pre-formed arylhydroxylamine metabolites in NHEK. Priming cells with cytokines did not significantly alter the cytotoxicity of the metabolites. The effect of pre-treatment with TNF-alpha on reactive oxygen species (ROS) generation in NHEK was also determined. While ROS formation in NHEK was increased in the presence of D-NOH, TNF-alpha did not alter the level of ROS generation. Our data suggest that the level of GSH reduction induced by pro-inflammatory cytokines does not predispose NHEK to cellular toxicity from either S-NOH or D-NOH.


Cytotoxic and apoptotic effects of 1,2-diborolanes with strong donor substitutes on human cancer cells.
In recent years, boron compounds have become more common as chemotherapy agents against certain types of cancers. Along with the development of boron-based therapeutic agents have come investigations into the various cancers and biochemical and molecular mechanisms affected by boron compounds and the relationships between boron compounds and chemical protection against cancer. In this preliminary study, the effects of new 1,2-N-substituted-1,2-diborolane derivatives on types of breast and liver cancers were examined for the first time. Four were found to significantly affect the cell viabilities and mitochondrial membrane potential changes in MCF-7, HepG2 and Hep3B cancer cells. Each was prepared in n-hexane at various concentrations (5, 10, 25, 50, 75 and 100 µg/mL). Human peripheral blood lymphocytes were used as control cells. Compounds 1, 2, 3a, and 3b 1,2-diborolane derivatives selectively killed cancer cells, but compound 1 was cytotoxic in a concentration-dependent manner on HepG2 and Hep3B and only at concentrations of at least 75 µg/mL on MCF-7 cells. Compound 3a exhibited cytotoxic effect on lymphocytes at 75 and 100 µgmL-1 concentrations, but compounds 1, 2 and 3b, 3c and 3d have not possessed significant cytotoxic effect on lymphocytes. Compounds 3c and 3d have not possessed significant cytotoxic effects. Mitochondrial membrane potential assay results supported these findings. Our results reveal that 1,2-diborolane derivates have high cytotoxic and apoptotic activities on human hepatocarcinoma cells and are therefore potential candidates in the development of new drugs against liver cancer.


The pheromone signal pathway in Saccharomyces cerevisiae.
Haploid cells of the yeast Saccharomyces cerevisiae normally undergo a budding life cycle, but after binding the appropriate mating pheromone they undergo a different developmental pathway that leads to conjugation. This intercellular communication between the two mating types activates a signal transduction pathway that stimulates the diverse physiological changes required for conjugation, such as induction of cell surface agglutinins, cell division arrest in G1, morphogenesis to form a conjugation tube, and cell fusion. The components of this pathway include a G protein-coupled receptor, several protein kinases, and a pheromone-responsive transcription factor. The molecular mechanisms that transduce the pheromone signal are remarkably similar to the mechanisms of hormone signaling used in multicellular organisms. Thus, the analysis of the pheromone signal pathway in yeast directly contributes to the study of cell growth and development in other eukaryotic organisms.


Ecotoxicity of cationic cellulose polymers to aquatic biota: The influence of charge density.
Better performances of cellulose-based polymers can be achieved by adjust their architecture including the density of cationic modifications. In this study, the influence of cationic substitution on the ecotoxicity of four quaternized hydroxyethyl cellulose polymers (SK-H, SK-L, SK-M, SK-MH) was studied, using an aquatic biota acute ecotoxicity classification, and rheological and physicochemical characterization. The ecotoxicity characterization was achieved by performing standard ecotoxicity assays with seven key trophic level species: Vibrio fischeri, Raphidocelis subcapitata, Chlorella vulgaris, Daphnia magna, Brachionus calyciflorus, Heterocypris incongruens, and Danio rerio. Median effective concentrations were used to compute hazard concentrations, through the species sensitive distribution curves method. The microalga C. vulgaris and rotifer B. calyciflorus were the most sensitive species to the studied polymers. The SK-H variant was highly toxic to the rotifer. Overall, variants with intermediate levels of cationic charge (SK-M, SK-MH) presented the lowest toxicity. The SK-M variant showed the lowest value of maximum acceptable concentration (0.00354 mg/L), thus being indicated as the least toxic variant. Therefore, the obtained results suggest that industry could direct the development of this type of polymers by tailoring its cationic substitution to moderate levels, in such a way that both functionality and environmental toxicity could be maximized.


Effects of short-term oral dosing of polychlorotrifluoroethylene (polyCTFE) on the rhesus monkey.
Polychlorotrifluoroethylene (polyCTFE--primarily oligomers with 3-4 monomer units), a non-flammable hydraulic fluid for aircraft, was given daily for 15 days by oral gavage to four Rhesus monkeys at a concentration of 0.725 g kg-1. The administered dose was at a level that had caused toxicity in rats. Steady-state blood and liver concentrations reached were the same in both species. In monkeys, polyCTFE did not cause the electrolyte, serum protein, liver enzyme and anemic disturbances previously seen in rats. Liver sections taken at 15 days, analyzed for palmitoyl Co-A beta-oxidation rates or by electron microscopy, showed no significant indication of peroxisomal proliferation. An increased blood urea nitrogen (BUN) at 15 days was the only clinical pathological abnormality seen in both monkeys and rats. Previously unobserved effects were increased triglycerides and glycogen depletion.


Nutritional access routes following oesophagectomy--a systematic review.
Nutritional support in patients undergoing oesophagectomy is of paramount importance in this usually malnourished patient group, but encountering significant clinical practice variation between units. Our aim was therefore to assess the strength of evidence behind nutritional support routes post-oesophagectomy. The Cochrane Library and Controlled Trials Registry, MEDLINE (Ovid) (1966-April 2009), PubMed, EMBASE (1966-April 2009), CINAHL, Web of knowledge and SCOPUS databases, were electronically searched for the highest level of evidence, with English language as a limit. Reference follow-up was also used. Studies were critically reviewed based on The NHS Public Health Resource Unit Critical Appraisal Skills Programme Tools. Five randomised control trials (RCTs) and one case-control trial, with 344 patients, were included in the review. There was a significant variation in the routes assessed (including intravenous fluid therapy, peripheral and central line nutrition, feeding jejunostomy, nasojejunal and nasoduodenal tubes) and the methodological quality of each study, with small patient numbers. No route was found to be superior over another in the RCTs. In the case-control trial, the combination of enteral parenteral nutrition led to shorter hospital stay compared with parenteral feeding alone. Nasojejunal and nasoduodenal tubes are associated with a significant rate of dislodgement. There is absence of strong direct evidence supporting a single feeding access route in oesophagectomy patients. Clinical decisions should be made based on available evidence from other types of gastrointestinal surgery, currently favouring enteral nutrition. If enteral feeding is chosen, feeding jejunostomy may be superior to nasojejunal or duodenal tubes.


Imaging diamagnetic susceptibility of collagen in hepatic fibrosis using susceptibility tensor imaging.
To characterize the magnetic susceptibility changes of liver fibrosis using susceptibility tensor imaging. Liver biopsy tissue samples of patients with liver fibrosis were obtained. Three-dimensional gradient-echo and diffusion-weighted images were acquired at 9.4 T. Susceptibility tensors of the samples were calculated using the gradient-echo phase signal acquired at 12 different orientations relative to the B0 field. Susceptibility anisotropy of the liver collagen fibers was quantified and compared with diffusion anisotropy, measured by DTI. For validation, a comparison was made to histology including hematoxylin and eosin staining, iron staining, and Masson's trichrome staining. Areas with strong diamagnetic susceptibility were observed in the tissue samples forming fibrous patterns. This diamagnetic susceptibility was highly anisotropic. Both the mean magnetic susceptibility and susceptibility anisotropy of collagen fibers exhibited a strong contrast against the surrounding nonfibrotic tissues. The same regions also showed an elevated diffusion anisotropy but with much lower tissue contrast. Masson's trichrome staining identified concentrated collagens in the fibrous regions with high susceptibility anisotropy, and a linear correlation was found between the susceptibility anisotropy and the histology-based staging. Diamagnetic susceptibility indicates the presence of collagen in the fibrotic liver tissues. Mapping magnetic susceptibility anisotropy may serve as a potential marker to quantify collagen fiber changes in patients with liver fibrosis.


Low cost, LoRa based river water level data acquisition system.
In recent years, climate change and catchment degradation have negatively affected stage patterns in rivers which in turn have affected the availability of enough water for various ecosystems. To realize and quantify the effects of climate change and catchment degradation on rivers, water level monitoring is essential. Various effective infrastructures for river water level monitoring that have been developed and deployed in developing countries over the years, are often bulky, complex and expensive to build and maintain. Additionally, most are not equipped with communication hardware components which can enable wireless data transmission. This paper presents a river water level data acquisition system that improves on the effectiveness, size, deployment design and data transmission capabilities of systems being utilized. The main component of the system is a river water level sensor node. The node is based on the MultiTech mDot - an ARM-Mbed programmable, low power RF module - interfaced with an ultrasonic sensor for data acquisition. The data is transmitted via LoRaWAN and stored on servers. The quality of the stored raw data is controlled using various outlier detection and prediction machine learning models. Simplified firmware and easy to connect hardware make the sensor node design easy to develop. The developed sensor nodes were deployed along River Muringato in Nyeri, Kenya for a period of 18 months for continuous data collection. The results obtained showed that the developed system can practically and accurately obtain data that can be useful for analysis of river catchment areas.


Medial rectus muscle pulley posterior fixation sutures in accommodative and partially accommodative esotropia with convergence excess.
The use of medial rectus pulley posterior fixation sutures to treat esotropia with convergence excess has limited support in the literature. We describe our results using this technique to treat patients with large near-distance disparities. We retrospectively analyzed records of patients with accommodative or partially accommodative esotropia and convergence excess 13(Δ) or greater treated with bilateral medial rectus muscle recessions augmented by pulley posterior fixation. Surgical doses of recessions were calculated for the mean of distance and near deviations. Primary outcome measures were ocular alignment at distance and near and near-distance disparity. A total of 26 patients were identified by the record review. Mean age at surgery was 5.4 years (range, 1.8-11.0 years) and mean follow-up time 12.7 months (range, 1.0-37.6 months). Mean preoperative distance esotropia was 22.9(Δ) (range, 0(Δ)-53(Δ)), with a mean near-distance disparity of 26.4(Δ) (range, 13(Δ)-53(Δ)). At 1 to 3 months postoperatively, mean distance deviation was 0.5(Δ) exotropia (range, 18(Δ) exotropia to 12(Δ) esotropia), with a statistically significant decrease in mean near-distance disparity to 4.5(Δ) (range, 0(Δ)-26(Δ); P < 0.001). Three-quarters of patients (77%) achieved 0(Δ) to 9(Δ) esotropia at 1 to 3 months, with 4 overcorrections for distance and 2 undercorrections for distance and near. At final follow-up 2 patients had persistent exotropia less than 10(Δ). Augmentation of bilateral medial rectus recessions with pulley posterior fixation resulted in a significant decrease in near-distance disparity in this group of patients with accommodative and partially accommodative esotropia and convergence excess, with a low rate of persistent overcorrection for distance.


Phylobioactive hotspots in plant resources used to treat Chagas disease.
Globally, more than six million people are infected with Trypanosoma cruzi, the causative protozoan parasite of the vector-borne Chagas disease (CD). We conducted a cross-sectional ethnopharmacological field study in Bolivia among different ethnic groups where CD is hyperendemic. A total of 775 extracts of botanical drugs used in Bolivia in the context of CD and botanical drugs from unrelated indications from the Mediterranean De Materia Medica compiled by Dioscorides two thousand years ago were profiled in a multidimensional assay uncovering different antichagasic natural product classes. Intriguingly, the phylobioactive anthraquinone hotspot matched the antichagasic activity of Senna chloroclada, the taxon with the strongest ethnomedical consensus for treating CD among the Izoceño-Guaraní. Testing common 9,10-anthracenedione derivatives in T. cruzi cellular infection assays demarcates hydroxyanthraquinone as a potential antichagasic lead scaffold. Our study systematically uncovers in vitro antichagasic phylogenetic hotspots in the plant kingdom as a potential resource for drug discovery based on ethnopharmacological hypotheses.


Quantitative metrics of the LV trabeculated layer by cardiac CT and cardiac MRI in patients with suspected noncompaction cardiomyopathy.
To compare cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) for the quantitative assessment of the left ventricular (LV) trabeculated layer in patients with suspected noncompaction cardiomyopathy (NCCM). Subjects with LV excessive trabeculation who underwent both CMR and CCT imaging as part of the prospective international multicenter NONCOMPACT clinical study were included. For each subject, short-axis CCT and CMR slices were matched. Four quantitative metrics were estimated: 1D noncompacted-to-compacted ratio (NCC), trabecular-to-myocardial area ratio (TMA), trabecular-to-endocardial cavity area ratio (TCA), and trabecular-to-myocardial volume ratio (TMV). In 20 subjects, end-diastolic and mid-diastolic CCT images were compared for the quantification of the trabeculated layer. Relationships between the metrics were investigated using linear regression models and Bland-Altman analyses. Forty-eight subjects (49.9 ± 12.8 years; 28 female) were included in this study. NCC was moderately correlated (r = 0.62), TMA and TMV were strongly correlated (r = 0.78 and 0.78), and TCA had excellent correlation (r = 0.92) between CMR and CCT, with an underestimation bias from CCT of 0.3 units, and 5.1, 4.8, and 5.4 percent-points for the 4 metrics, respectively. TMA, TCA, and TMV had excellent correlations (r = 0.93, 0.96, 0.94) and low biases (- 3.8, 0.8, - 3.8 percent-points) between the end-diastolic and mid-diastolic CCT images. TMA, TCA, and TMV metrics of the LV trabeculated layer in patients with suspected NCCM demonstrated high concordance between CCT and CMR images. TMA and TCA were highly reproducible and demonstrated minimal differences between mid-diastolic and end-diastolic CCT images. The results indicate similarity of CCT to CMR for quantifying the LV trabeculated layer, and the small differences in quantification between end-diastole and mid-diastole demonstrate the potential for quantifying the LV trabeculated layer from clinically performed coronary CT angiograms. • Data on cardiac CT for quantifying the left ventricular trabeculated layer are limited. • Cardiac CT yielded highly reproducible metrics of the left ventricular trabeculated layer that correlated well with metrics defined by cardiac MR. • Cardiac CT appears to be equivalent to cardiac MR for the quantification of the left ventricular trabeculated layer.


Three-dimensional portable document format: a simple way to present 3-dimensional data in an electronic publication.
Three-dimensional (3D) models of teeth and soft and hard tissues are tessellated surfaces used for diagnosis, treatment planning, appliance fabrication, outcome evaluation, and research. In scientific publications or communications with colleagues, these 3D data are often reduced to 2-dimensional pictures or need special software for visualization. The portable document format (PDF) offers a simple way to interactively display 3D surface data without additional software other than a recent version of Adobe Reader (Adobe, San Jose, Calif). The purposes of this article were to give an example of how 3D data and their analyses can be interactively displayed in 3 dimensions in electronic publications, and to show how they can be exported from any software for diagnostic reports and communications among colleagues.


Long-term prevention of allergic diseases by using protein hydrolysate formula in at-risk infants.
This prospective, long-term study assessed the effects of a protein hydrolysate formula on allergy prevention in infants with a family history of allergy. Infants were randomly assigned to receive either the hydrolysate formula (n = 92) or an adapted cow milk formula (n = 85) alone or with breast-feeding for 4 months. The groups did not differ in family allergy history scores or cord blood IgE levels. After 4 months, total IgE levels and allergic reactions did not differ significantly between groups, although the hydrolysate group had a lower prevalence of eczema. At 12 months of age, neither IgE levels nor allergic reactions were significantly different. At 2 years of age, however, 18 allergic reactions had occurred in the hydrolysate group and 31 had occurred in the control group; the differences were significant for eczema (p < 0.001) but not for asthma. At 4 years of age, allergic signs were found in 11 children in the hydrolysate group and in 17 children in the control group; the difference was significant only for eczema (p < 0.01). These results suggest that early feeding of a protein hydrolysate formula to infants at risk for allergies had a long-term preventive effect on the prevalence of eczema but not of asthma.


Activation of MyoD-dependent transcription by cdk9/cyclin T2.
Myogenic transcription is repressed in myoblasts by serum-activated cyclin-dependent kinases, such as cdk2 and cdk4. Serum withdrawal promotes muscle-specific gene expression at least in part by down-regulating the activity of these cdks. Unlike the other cdks, cdk9 is not serum- or cell cycle-regulated and is instead involved in the regulation of transcriptional elongation by phosphorylating the carboxyl-terminal domain (CTD) of RNA polymerase II. While ectopic expression of cdk2 together with its regulatory subunits (cyclins E and A) inhibits myogenic transcription, overproduction of cdk9 and its associated cyclin (cyclin T2a) strengthens MyoD-dependent transcription and stimulates myogenic differentiation in both MyoD-converted fibroblasts and C2C12 muscle cells. Conversely, inhibition of cdk9 activity by a dominant negative form (cdk9-dn) represses the myogenic program. Cdk9, cyclinT2 and MyoD can be detected in a multimeric complex in C2C12 cells, with the minimal cdk9-binding region of MyoD mapping within 101-161 aa of the bHLH region. Finally, cdk9 can phosphorylate MyoD in vitro, suggesting the possibility that cdk9/cycT2a regulation of muscle differentiation includes the direct enzymatic activity of the kinase on MyoD.


Modified Eversion Carotid Endarterectomy (mECEA): Analysis of Clinical and Financial Outcomes.
Several carotid endarterectomy techniques have been described, including conventional carotid endarterectomy (CCEA) performed with patch repair and eversion carotid endarterectomy (ECEA) performed with transection of the internal carotid artery. We describe our simplified technique of modified eversion carotid endarterectomy (mECEA) with longitudinal arteriotomy limited to the carotid bulb, without transection of the internal carotid artery and present our analysis of its safety, efficacy, and cost effectiveness. A retrospective review of all carotid endarterectomies performed by 3 vascular surgeons over a 3-year period was completed. About 197 mECEA were performed during the study period. Follow-up data were obtained on 77.7% of patients. A comparison was made with the contemporary literature with respect to outcomes for both CCEA and ECEA. Between January 2012 and December 2014, a total of 197 mECEA were performed. The perioperative stroke and death rates for those undergoing mECEA was 0.5% and 0.5%, respectively. Late stroke and death rates were 3.0% and 5.1%, respectively. Perioperative rate of myocardial infarction was 1.0%. Early restenosis rates of >70% occurred in 1.4%, whereas late restenosis of >70% occurred in 2.7%. Mean operating time for those undergoing mECEA was 57.9 min. Average costs savings for mECEA compared to CCEA were $5,835. This simplified technique has comparable outcomes to those described in the contemporary literature for both CCEA and ECEA with respect to postoperative neurologic events as well as restenosis rates. In our institution, the short mean operative times with mECEA has led to reduced resource utilization.


Endo-extralaryngeal needle carrier instrument.
The author reports on an instrument which is suitable for stitching from inside to outside under laryngomicroscopic control without opening the larynx. The instrument, as well as the operation techniques based on the instrument, permit the simple treatment of vocal cord synechiae and of laryngostenosis consequent to bilateral paralysis of the recurrent laryngeal nerve.


Indomethacin enhancement of spleen-cell responsiveness to mitogen stimulation in tumorous mice.
Spleen cells removed from C57Bl/6J mice bearing a methylcholanthrene-induced fibrosarcoma (MC-16) demonstrate suppressed responsiveness of phytohemagglutinin (PHA) and bacterial lipopolysaccharide (LPS) induced mitogenesis as compared to non-tumorous mice. A similar depression of PHA-induced mitogenesis was observed with spleen cells from C3H/HeJ mice bearing syngeneic mammary adenocarcinomas (C3HBA). The administration of indomethacin, a non-competitive irreversible prostaglandin (Pg) synthesis inhibitor, (75 or 100 mug/mouse, IP) on an alternate day basis to groups of tumor-bearing mice of both strains, significantly enhanced immune cell responsiveness to mitogenic stimulation. The addition of indomethacin (10 mug/ml) to cultures of spleen cells from these tumor-bearing mice, as well as to DBA/1J mice bearing the Cloudman S-91 melanoma, enhanced spleen-cell responsiveness to mitogen-induced DNA synthesis by as much as 156%. Indomethacin administration in vivo or in vitro had no significant effect on mitogen-induced DNA synthesis of spleen cells from non-tumor-bearing animals. It is hypothesized that tumors, or tumor-cell antigens, increase Pg production of a population of spleen cells, and that the increased Pg content of the spleen may be important in controlling immune responsiveness in mice.


Influence of denture brushing on the surface properties and color stability of CAD-CAM, thermoformed, and conventionally fabricated denture base resins.
To assess the influence of denture brushing on the surface roughness, hardness, and color stability of conventional, thermoformed, and CAD-CAM denture base materials. Seven different denture base materials were included in this study; conventional heat-polymerized acrylic resin (PMMA) served as control, polyamide, acetal, two categories of milled acrylic discs (AvaDent and IvoCad), and two categories of 3D-printed resins (NextDent and FormLabs). The specimens were constructed according to manufacturers' instructions and then subjected to simulated brushing (20,000 cycles). According to the brushing method, the specimens were split into three groups, no brushing, brushing with water, and brushing with toothpaste. Surface roughness, hardness, and color change were evaluated before and after brushing. Collected data were analyzed using ANOVA, and post-hoc Tukey's tests (α = 0.05). A significant difference was noted between the surface roughness of the tested materials before and after denture brushing (p < 0.05), and milled resin showed the least Ra values. Denture brushing with water significantly increased the Ra of PMMA (p = 0.004) and IvoCad (p = 0.032), while brushing using toothpaste did not show a significant increase. The brushing protocols did not alter the hardness of tested materials except that of PMMA (p = 0.001). The color stability of the tested materials showed comparable results with both brushing protocols. The tested properties showed variations between the types of denture base resins. Hardness and color stability of CAD-CAM and thermoformed denture base resins were not altered by denture brushing and showed comparable results with both brushing methods. Surface roughness was the only property that showed alteration after denture brushing.


Promoting adherence to psychopharmacological treatment among prisoners with mental health problems: Follow-up of a randomized controlled trial.
This study presents follow-up results regarding a treatment adherence programme (TAP) for prisoners, the initial effectiveness of which we previously evaluated in a randomized controlled trial. Here we used an experimental design with two randomized groups and assessment at four time points: baseline (pre-intervention), at 3 months (post-intervention), and at 6 and 9 months after baseline. Participants were 151 prisoners with mental health problems (Mage = 41.85, SD = 10.31) who were randomly assigned to either the TAP or treatment as usual (TAU). Prisoners who completed the TAP showed a greater improvement in treatment adherence at 3 and 9 months, compared with those who received TAU. There were no significant differences between the groups in subjective well-being under medication. The availability of an easy-to-apply, universal programme that is able to promote treatment adherence in the prison context could make a positive contribution to the general health of inmates.


Antioxidative effects of N-acetylcysteine, lipoic acid, taurine, and curcumin in the muscle of Cyprinus carpio L. exposed to cadmium.
We investigated the muscle tissue of a teleost Cyprinus carpio L. to find out whether N-acetylcysteine (NAC), alpha-lipoic acid (LA), taurine (TAU), and curcumin (CUR) were able to counteract oxidative stress induced by acute exposure to cadmium (Cd). The muscle tissue was dissected 96 h after a single intraperitoneal injection of Cd (5 mg kg(-1)) and of antioxidant substances (50 mg kg(-1)). Using spectrophotometry, we determined the glutathione redox status, lipid peroxidation levels and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione disulphide reductase (GR). Accumulation of Cd in the muscle was analysed using inductively coupled plasma - optical emission spectrometry (ICP-OES).All substances lowered Cd levels in the following order of efficiency; LA=NAC>TAU=CUR. Cadmium increased SOD activity, but CAT activity declined, regardless of antioxidant treatment. Treatment with CUR induced GPx activity. Treatment with TAU lowered Cd due to higher total glutathione (tGSH). The most effective substances on lipid peroxidation were LA and NAC due to a greater Cd-lowering potential. It seems that the protective role of TAU, LA, and NAC is not necessarily associated with antioxidant enzymes, but rather with their own activity.


Scintillation Proximity Assay (SPA)-Based Radioligand Binding for PPARα, PPARγ, and PPARδ Receptors.
Peroxisome proliferator-activated receptors (PPARs) have been exploited as drug targets for combating multiple diseases. Several activators with different selectivity for the PPAR α, γ, and δ subtypes have been introduced into the market or have reached advanced clinical trials. Binding assays are of utmost importance for the discovery and profiling of such PPAR ligands. Binding assays are often based on radioligands, in particular, tritiated molecules are applied. We developed synthetic procedures for tritiating various PPAR agonists and applied these radioligands for setting up a scintillation proximity assay (SPA) for PPAR α, γ, and δ. These SPAs allow to assess the binding affinities of PPAR α, γ, and δ ligands, along with their respective subtype selectivity profiles. Therefore, SPA is an important tool for hit discovery and lead optimization campaigns aimed at identifying next-generation PPAR ligands.


Teaching banking skills to mildly mentally retarded adolescents.
In this study, two experiments evaluated a classroom training program designed to teach basic banking skills to three mildly mentally retarded adolescents. The participants were taught to open savings and checking accounts during Experiment I and to conduct banking transactions during Experiment II. The banking transaction skills acquired in Experiment II maintained at high levels and generalized to two novel environments for two participants, whereas moderate generalization and maintenance scores were obtained by the third participant. The average performance of the mentally retarded participants compared favorably with the scores obtained by 10 college student volunteers in both the percentage of correct responses and the pattern of incorrect responses.


NSAIDs, gastrointestinal toxicity and inflammatory bowel disease.
Non-steroidal antiinflammatory drugs (NSAIDs) are currently one of the most widely used drugs. The use of NSAIDs is associated with gastrointestinal toxicity, affecting both upper gastrointestinal tract (peptic ulcer disease) and lower gastrointestinal tract (NSAID-induced enteropathy). NSAIDs use has been associated with an increased risk of clinical relapse in inflammatory bowel disease patients. In this article, we review the upper and lower gastrointestinal toxicity of NSAIDs, with a focus on the risks and specific data of these drugs in inflammatory bowel disease patients, giving recommendations for its appropriate use in the clinical practice. Although evidence is scarce, short-term use of NSAIDs appears to be safe, and the data available suggest that selective COX-2 inhibitors are the safer option. NSAIDs should be avoided as long-term treatment or with high doses, especially in patients with active inflammation.


Courses of diabetic retinopathy.
A follow-up study on 93 patients suffering from diabetic preretinopathy showed different courses of development. Predominantly occlusive types of microangiopathy were significantly more predisposed to a rapid progression of lesions than predominantly exudative types or occlusive exudative types. In addition, transition of one type into the other and reversibility of all symptoms were observed.


Meningitis due to Haemophilus influenzae type e biotype 4.
Haemophilus influenzae type e biotype 4 was isolated from the cerebrospinal fluid of a 16-month-old child with meningitis. This is the first isolation, from a case of meningitis, of this organism that has been biotyped.


An outcome study on complications using routine ultrasound assistance for internal jugular vein cannulation.
Ultrasound guidance for central venous cannulation is advised by recent guidelines, but is not being applied in everyday practice. The purpose of this study was to determine the reduction in complications when applying an ultrasound locating device for internal jugular vein catheterization. An observational study was conducted from November 2004 to October 2005 in a tertiary neurosurgical hospital on 300 patients undergoing internal jugular vein cannulation using an ultrasound technique. Patients were not randomized and operators were trained using theoretical and practical courses. Prior to the study, the investigators, who were consultant anaesthesiologists, had to perform at least 20 successful supervised cannulations. Cannulation was successful in all cases. The incidence of arterial puncture was 2.7%, and multiple venous punctures represented the main minor complication (14%). Bivariate analysis of the overall complications revealed no significant correlation with age group, American Society of Anesthesiologists' (ASA) classification, body mass index, or position and diameter of the vein. Ultrasound cannulation of the internal jugular vein minimized complications. These could be avoided when new ultrasound probes and specific needles are introduced.


Non-linear enhancement of mRNA delivery efficiencies by influenza A derived NS1 protein engendering host gene inhibition property.
Nucleic acid induced immunogenicity remains a significant impediment in biomedical therapeutics because the innate immune system is a complex network overlaid with functional redundancies. Herein we report that non-structural protein 1 (NS1), an immune evasion protein derived from influenza A virus, when co-delivered in mRNA format is a potent mRNA transfection enhancer without toxicity. Transfection enhancement is mediated by NS1's effector domain through inhibition of IRF3 and PKR, activators of early anti-viral responses as well as CPSF30, a non immunostimulating protein. Importantly, host gene inhibition mediated via CPSF30 inhibition is a highly effective immune evasion mechanism because it blocks de novo gene expression non-specifically and inhibits global anti-viral responses during mRNA transfection. We show that only NS1 with CPSF30 inhibition property can enhance modified mRNA transfections. Furthermore, transfection efficiency of unmodified mRNA, if co-delivered with NS1-TX91 mRNA, can exceed that of modified mRNA in HepG2, RAW 264.7 and HeLa cells. The novel impact of NS1-TX91 lays the foundation of a virus inspired immune evasion genes co-delivery approach that can address problems arising from RNA immunogenicity for non-vaccine mRNA therapeutics in an affordable and scalable way. It is also transferable to applications that benefits from active inhibition of material-induced immunogenicity.


Intraindividual comparison of MRI-derived liver surface nodularity score at 1.5 T and 3 T.
To compare the MRI-derived liver surface nodularity (LSN) scores acquired on both 1.5 T and 3 T. Forty chronic liver disease patients who underwent gadoxetic acid-enhanced MRI at both 1.5 and 3 T were included. Axial hepatobiliary phase images with the same voxel size were used to calculate the LSN score in both liver lobes with a quantitative software. Rank correlation, Wilcoxon test, and Bland-Altman limits of agreement were used for statistical analysis. There was a weak correlation between the right and left liver lobe on 1.5 T (rs = 0.331, p = 0.037) and 3 T (rs = 0.381, p = 0.015). The correlation between 1.5 T and 3 T on both liver lobes showed a very strong correlation (right, rs = 0.927, p < 0.001; left, rs = 0.845, p < 0.001). LSN scores differed significantly between both lobes on 1.5 T (median, 1.201 vs. 0.674, right vs. left) and 3 T (1.076 vs. 0.592) (all p < 0.001). LSN scores differed significantly between 1.5 T and 3 T on both lobes (all p < 0.001). The Bland-Altman plot comparing 1.5 T and 3 T on right and left liver lobes showed a systemic bias of 0.08 and 0.07, respectively. LSN scores differed significantly on 1.5 T vs. 3 T and right vs. left liver lobe. Caution should be made when comparing LSN scores derived from different field strengths or the hepatic lobe. Interplatform, interlobar reproducibility should be resolved to use LSN scores, which is relatively easy to perform without additional hardware or images.


Effect of leukemia inhibitory factor on human cytotrophoblast differentiation along the invasive pathway.
Leukemia inhibitory factor (LIF) is a pleiotropic secreted cytokine that was shown to be essential for blastocyst implantation in mice. Since it is well documented that LIF is produced by the human endometrium, we wondered if this cytokine was capable of modulating the invasive behaviour of human cytotrophoblastic cells (CTB). CTB were isolated and purified from first trimester abortions, separated or not into cells bearing a laminin or a fibronectin receptor (alpha 6 beta 4 or alpha 5 beta 1 respectively) using specific monoclonal antibodies and magnetic particles. We observed that rhLIF inhibited the secretion of gelatinases and of hCG by CTB but remained without effects on the secretion of fetal fibronectin (fFN). These effects were exerted on different CTB subsets: although rhLIF inhibited the secretion of gelatinases by alpha 6 positive cells, it stimulated the fFN secretion by alpha 5 positive cells. The inhibitory effect of rhLIF on the secretion of hCG was mainly due to its effect on the hCG secretion of alpha 5 positive CTB. Taken together these results suggest that in vitro LIF inhibits the differentiation of CTB towards an invasive phenotype by inhibiting the secretion of metalloproteinases, by increasing the deposition of fFN into the extracellular matrix and by inhibiting the differentiation of CTB into syncytium.


Use of molecular diagnostics in sexually transmitted diseases. Critical assessment.
This review describes and assesses the use of molecular assays for the diagnosis of sexually transmitted diseases (STDs). Specifically, data from literature on currently available commercial systems as well as that of imminently to be released assay formats are presented. The focus is on evaluations of two molecular diagnostic techniques--hybridization and amplification for the direct detection of Chlamydia trachomatis and Neisseria gonorrhoeae (gonococci, GC)--the use of urine as a specimen for the diagnosis of these pathogens in humans, a confirmatory probe assay for GC, and finally the description of a hybridization assay for pathogens significant in vaginitis and bacterial vaginosis. Although viral pathogens are a significant part of the STD problem, and molecular techniques have been described for their identification, they are not being discussed here. With the exception of the Virapap DNA hybridization assay for human papillomavirus (Digene Diagnostic, Silver Spring, MD), suitable molecular clinical laboratory assays for viral detection have not been developed for genital samples.


Replication and transcription: shaping the landscape of the genome.
As the relationship between nuclear structure and function begins to unfold, a picture is emerging of a dynamic landscape that is centred on the two main processes that execute the regulated use and propagation of the genome. Rather than being subservient enzymatic activities, the replication and transcriptional machineries provide potent forces that organize the genome in three-dimensional nuclear space. Their activities provide opportunities for epigenetic changes that are required for differentiation and development. In addition, they impose physical constraints on the genome that might help to shape its evolution.


Factors influencing delayed gastric emptying after pylorus-preserving pancreatoduodenectomy.
Delayed gastric emptying (DGE) is the most frequent postoperative complication after pylorus-preserving pancreatoduodenectomy (PPPD). This study was undertaken to determine which factors influence the development of DGE after PPPD. We studied 150 consecutive patients who underwent PPPD performed by one surgeon between 1996 and 2000. The variables analyzed were age, gender, diagnosis, laboratory data, operative time, transfusion, preoperative cholangitis, and complications. The operative factors included were route of the afferent jejunal limb (retromesenteric versus antemesenteric), type of pancreatoenteric anastomosis, and preservation of the right gastric artery. DGE was defined as nasogastric drainage for more than 10 days or delay of regular diet until 14 days postoperatively. Univariate analysis showed preoperative cholangitis, intraabdominal complication, and the jejunal reconstruction method were significantly associated with DGE. Preservation of the right gastric artery was not associated with gastric emptying ability. Multivariate analysis by logistic regression showed that DGE was significantly more frequent among patients with preoperative cholangitis (15 of 36 [41.7%] versus 19 of 114 [16.7%], p=0.0031), postoperative intraabdominal complications (15 of 36 [41.7%] versus 10 of 114 [8.8%], p = 0.0001), and in the retromesenteric group (33 of 104 [31.7%] versus 3 of 46 [6.5%], p = 0.0174). Preoperative cholangitis and postoperative leakage problems affect gastric emptying after PPPD during the early postoperative period. The retromesenteric route is not recommended for pancreato- and biliary-enteric anastomosis. We speculate that retromesenteric passage of afferent jejunum can cause venous congestion and bowel edema, which can in turn retard the recovery of jejunal peristalsis at the duodenojejunostomy site resulting in disturbance from food passage.


Web-based tool for cancer family history collection: A prospective randomized controlled trial.
Approximately 1% of individuals have a hereditary cancer predisposition syndrome, however, the majority are not aware. Collecting a cancer family history (CFH) can triage patients to receive genetic testing. To rigorously assess different methods of CFH collection, we compared a web-based tool (WBT) to usual care (clinician collects CFH) in a randomized controlled trial. New gynecologic oncology patients (seen 9/2019-9/2021) were randomized to one of three arms in a 2:2:1 allocation ratio: 1) usual care clinician CFH collection, 2) WBT completed at home, or 3) WBT completed in office. The WBT generated a cancer-focused pedigree and scores on eight validated cancer risk models. The primary outcome was collection of an adequate CFH (based on established guidelines) with usual care versus the WBT. We enrolled 250 participants (usual care - 110; WBT home - 105; WBT office - 35 [closed early due to COVID-19]). Within WBT arms, 109 (78%) participants completed the tool, with higher completion for office versus home (33 [94%] vs. 76 [72%], P = 0.008). Among participants completing the WBT, 63 (58%) had an adequate CFH versus 5 (5%) for usual care (P < 0.001). Participants completing the WBT were significantly more likely to complete genetic counseling (34 [31%] vs. 15 [14%], P = 0.002) and genetic testing (20 [18%] vs. 9 [8%], P = 0.029). Participant and provider WBT experience was favorable. WBTs for CFH collection are a promising application of health information technology, resulting in more comprehensive CFH and a significantly greater percentage of participants completing genetic counseling and testing.


Extraction of cardiac and respiratory motion cycles by use of projection data and its applications to NMR imaging.
A technique of extracting cardiac and respiratory motion cycles by use of projection data is proposed and studied. These extracted cardiac and respiratory motion cycles are applied to the cine imaging of heart and motion artifact reduction in abdominal imaging instead of the conventional ECG gating devices. The basic concepts and their applications are discussed. Experimental results on human volunteers obtained with the KAIS 2.0-T whole-body NMR imaging system together with the pulse sequences used for the experiments are presented.


Direct purification of recombinant hepatitis B core antigen from two different pre-conditioned unclarified Escherichia coli feedstocks via expanded bed adsorption chromatography.
Direct recovery of hepatitis B core antigen (HBcAg) from unclarified Escherichia coli homogenates via expanded bed adsorption chromatography (EBA) has been explored in this study. Streamline DEAE was selected as the anion exchanger to recover HBcAg from heat-treated and non-heat-treated unclarified feedstocks. The use of anion-exchanger for direct extraction of proteins from unclarified feedstock is not preferred due to lack of specificity of its ligand. In this study, thermal treatment of the unclarified feedstock at 60 degrees C has resulted in 1.2- and 1.8-fold increases in yield and purity of HBcAg, respectively, compared with that purified from non-heat-treated feedstock. Heating the crude feedstock has resulted in denaturation and precipitation of contaminants in the feedstock, hence reducing non-specific interactions between the cell debris and adsorbent. The selectivity of the anion-exchanger has also been increased as shown in the breakthrough curve obtained. Enzyme-linked immunosorbent assay showed that the antigenicity of the HBcAg from heat-treated unclarified feedstock is still preserved.


Standard v lightweight wheelchair propulsion in spinal cord injured patients.
Twenty-six male SCI subjects (six quadriplegics, eight "high paraplegics," and 12 "low paraplegics") propelled both standard and lightweight wheelchairs at a "sprint pace" (Sp) for 400 feet, and at a "duration pace" (Du) for four continuous minutes. Pulse, blood pressure and respirations were measured before and after each trial, and V was calculated. Appropriate training and rest periods were given; order of wheelchair testing was randomized. A questionnaire was later administered. Variations in pulse, systolic blood pressure, and respirations were significant between myelopathic levels (P less than 0.01), but were not affected by the type of wheelchair used. Quadriplegic V was less (P less than 0.01) than that of either paraplegic group for Sp and Du trials; for Sp, lightweight wheelchair V is faster (P less than 0.01) than standard wheelchair V for all groups.


Influence of land development on stormwater runoff from a mixed land use and land cover catchment.
Mitigating for the negative impacts of stormwater runoff is becoming a concern due to increased land development. Understanding how land development influences stormwater runoff is essential for sustainably managing water resources. In recent years, aggregate low impact development-best management practices (LID-BMPs) have been implemented to reduce the negative impacts of stormwater runoff on receiving water bodies. This study used an integrated approach to determine the influence of land development and assess the ecological benefits of four aggregate LID-BMPs in stormwater runoff from a mixed land use and land cover (LULC) catchment with ongoing land development. It used data from 2011 to 2015 that monitored 41 storm events and monthly LULC, and a Personalized Computer Storm Water Management Model (PCSWMM). The four aggregate LID-BMPs are: ecological (S1), utilizing pervious covers (S2), and multi-control (S3) and (S4). These LID-BMPs were designed and distributed in the study area based on catchment characteristics, cost, and effectiveness. PCSWMM was used to simulate the monitored storm events from 2014 (calibration: R2 and NSE>0.5; RMSE <11) and 2015 (validation: R2 and NSE>0.5; RMSE <12). For continuous simulation and analyzing LID-BMPs scenarios, the five-year (2011 to 2015) stormwater runoff data and LULC change patterns (only 2015 for LID-BMPs) were used. Results show that the expansion of bare land and impervious cover, soil alteration, and high amount of precipitation influenced the stormwater runoff variability during different phases of land development. The four aggregate LID-BMPs reduced runoff volume (34%-61%), peak flow (6%-19%), and pollutant concentrations (53%-83%). The results of this study, in addition to supporting local LULC planning and land development activities, also could be applied to input data for empirical modeling, and designing sustainable stormwater management guidelines and monitoring strategies.


The impact of accountability on local officials' behavior in the pandemic prevention and control in China based on utility maximization.
The COVID-19 pandemic is a public health crisis and an inspection of national governance systems and crisis response capabilities of countries globally. China has adopted a tough accountability system for officials and has succeeded in containing the spread of the pandemic. This study aimed to assess the impact of accountability on local officials' behavior in the pandemic prevention and control based on the official promotion tournament theory and utility maximization analysis framework. The panel data of 237 Chinese cities were extracted with local officials' characteristics, confirmed cases, Baidu migration index, Baidu search index according to city names, and data were excluded with local officials' relocation or sub-provincial cities between January 1, 2020 and May 5, 2020. Promotion gain and accountability cost were constructed by adopting promotion speed indicator, and the research hypotheses were assumed based on the utility maximization. It was the first time to apply the interaction model to empirically investigate the relationship between the promotion speed of local officials and the COVID-19 confirmed cases. Our study showed that the promotion speed of provincial governors and mayors significantly affected the number of confirmed cases (β = - 11.615, P < 0.01). There was a significant interaction between the promotion speeds of provincial governors and mayors (β = - 2594.1, P < 0.01), indicating that they had a coordinated effect on the pandemic control. Additionally, mayors with different promotion speeds made a significant difference in controlling the imported cases and those who promoted faster better controlled the imported cases (β = - 0.841, P < 0.01). Mayors with full-time postgraduate education, titles, and majors in science and engineering had a better effect on controlling the number of confirmed cases. Our study provides evidence that the official accountability system has played an important role in containing the pandemic, which suggests that local officials motivated by the accountability system would respond to the pandemic actively for higher utility. Furthermore, provincial governors and mayors have played a coordinated effect in pandemic control. The above evidences reveal that implementing the official accountability system could improve the government's emergency management capability and the efficiency of pandemic control. Therefore, adopting a strict accountability system could be effective in pandemic containment globally, especially in centralized countries.


Comprehensive molecular and clinical characterization of SLC1A5 in human cancers.
Although SLC1A5 has been reported to be closely associated with some cancer types, a comprehensive and systematic assessment of SLC1A5 across human cancers is lacking. Thus, Pan-cancer analysis of SLC1A5 was performed across 30 types of human cancers in this study. We examined mRNA expression, protein expression, copy number variation (CNV), DNA methylation, clinical relevance, cell functions, drug response and total immune infiltrates of SLC1A5 in more than 9000 patients across 30 human cancer types from The Cancer Genome Atlas (TCGA) dataset. Additionally, nine independent Gene Expression Omnibus datasets, more than 800 cancer cell lines from the Cancer Cell Line Encyclopedia dataset and the Project Achilles dataset were used to validate our findings in the TCGA dataset. Landscapes of SLC1A5 were established across multiple cancers. We showed that SLC1A5 is upregulated in multiple cancers, particularly in digestive and respiratory system cancers. SLC1A5 upregulation may be driven by CNV gain and DNA hypomethylation in human cancers. Furthermore, SLC1A5 overexpression is associated with tumor progression and poor survival in multiple cancers. Moreover, we systematically explored the potential effects of SLC1A5 expression on cell functions and drug response in human cancers. SLC1A5 knockdown showed significant proliferation-inhibiting effects in most human cancer types, especially in the digestive system and KRAS-mutant cancers. SLC1A5 expression is associated with proliferation activities of KRAS-mutant cancer cell lines and drug response of many anti-cancer drugs. Finally, we demonstrated that SLC1A5-realted tumor immune microenvironment characteristics showed strong heterogeneity in human cancers. Taken together, our findings highlight the important roles of SLC1A5 in tumorigenesis, progression, prognosis and therapy.


Anion Exchange Composite Membranes Composed of Quaternary Ammonium-Functionalized Poly(2,6-dimethyl-1,4-phenylene oxide) and Silica for Fuel Cell Application.
Anion exchange membranes (AEMs) with good alkaline stability and ion conductivity are fabricated by incorporating quaternary ammonium-modified silica into quaternary ammonium-functionalized poly(2,6-dimethyl-1,4-phenylene oxide) (QPPO). Quaternary ammonium with a long alkyl chain is chemically grafted to the silica in situ during synthesis. Glycidyltrimethylammoniumchloride functionalization on silica (QSiO2) is characterized by Fourier transform infrared and transmission electron microscopic techniques. The QPPO/QSiO2 membrane having an ion exchange capacity of 3.21 meq·g-1 exhibits the maximum hydration number (λ = 11.15) and highest hydroxide ion conductivity of 45.08 × 10-2 S cm-1 at 80 °C. In addition to the high ion conductivity, AEMs also exhibit good alkaline stability, and the conductivity retention of the QPPO/QSiO2-3 membrane after 1200 h of exposure in 1 M potassium hydroxide at room temperature is about 91% ascribed to the steric hindrance offered by the grafted long glycidyl trimethylammonium chain in QSiO2. The application of the QPPO/QSiO2-3 membrane to an alkaline fuel cell can yield a peak power density of 142 mW cm-2 at a current density of 323 mA cm-2 and 0.44 V, which is higher than those of commercially available FAA-3-50 Fumatech AEM (OCV: 0.91 V; maximum power density: 114 mW cm-2 at current density: 266 mA cm-2 and 0.43 V). These membranes provide valuable insights on future directions for advanced AEM development for fuel cells.


Adaptation of pancreatic amylase activity to enhanced parenteral carbohydrate intake in rats, and electron microscopic findings.
The present study records a rise of amylase activity in rat pancreatic tissue after a long-term administration of high carbohydrate diets (14% excess of glucose administered orally or subcutaneously as 30% glucose solution) in comparison to a normal diet. It was concluded that the pancreas obtains information on intestinal food composition along the humoral pathway. Electron microscopic investigations revealed no impairment of the acinar cells of the pancreas, but only changes that may be considered as a structural expression of the various phases of activity of the acinar cells.


The effect of computers for weight loss: a systematic review and meta-analysis of randomized trials.
The use of computers to deliver education and support strategies has been shown to be effective in a variety of conditions. We conducted a systematic review and meta-analysis to evaluate the impact of computer-based technology on interventions for reducing weight. We searched MEDLINE, CENTRAL, CINAHL, PsycINFO, Google Scholar and ClinicalTrials.gov (all updated through June 2010) for randomized controlled trials evaluating the effect of computer-based technology on education or support interventions aimed at reducing weight in overweight or obese adults. We calculated weighted mean differences (WMD) and 95% confidence intervals (CI) using random effects models. Eleven trials with 13 comparisons met inclusion criteria. Based on six comparisons, subjects who received a computer-based intervention as an addition to the standard intervention given to both groups lost significantly more weight (WMD -1.48 kg, 95% CI -2.52, -0.43). Conversely, based on six comparisons, subjects for whom computer-based technology was substituted to deliver an identical or highly comparable intervention to that of the control group lost significantly less weight (WMD 1.47 kg, 95% CI 0.13, 2.81). Significantly different weight loss seen in "addition" comparisons with less than six months of follow-up (WMD -1.95 kg, 95% CI -3.50, -0.40, two comparisons) was not seen in comparisons with longer follow-up (-1.08 kg, 95% CI -2.50, 0.34, four comparisons). Analyses based on quality and publication date did not substantially differ. While the addition of computer-based technology to weight loss interventions led to statistically greater weight loss, the magnitude (<1.5 kg) was small and unsustained.


Soret and Dufour effects on a Casson nanofluid flow past a deformable cylinder with variable characteristics and Arrhenius activation energy.
In this study, the effects of variable characteristics amalgamated with chemical reaction and Arrhenius activation energy are analyzed on a two-dimensional (2D) electrically conducting radiative Casson nanoliquid flow past a deformable cylinder embedded in a porous medium. The surface of the cylinder is deformable in the radial direction i.e., the z-axis. The impression of Soret and Dufour's effects boosts the transmission of heat and mass. The flow is analyzed numerically with the combined impacts of momentum slip, convective heat, and mass conditions. A numerical solution for the system of the differential equations is attained by employing the bvp4c function in MATLAB. The dimensionless protuberant parameters are graphically illustrated and discussed for the involved profiles. It is perceived that on escalating the velocity slip parameter and porosity parameter velocity field depreciates. Also, on escalating the radiation parameter and heat transfer Biot number a prominent difference is noticed in an upsurge of the thermal field. For growing values of Brownian motion and thermophoretic parameters, temperature field augments. On escalating the curvature parameter and porosity parameter, drag force coefficient upsurges. The outcome of the Soret number, mass transfer Biot number, and activation energy parameter is quite eminent on the concentration distribution for the sheet in comparison to the deformable cylinder. A comparative analysis of the present investigation with an already published work is also added to substantiate the envisioned problem.


Effect of the Endocannabinoid System in Memory Updating and Forgetting.
Most memories of life experiences will be forgotten or modified over time. Although several studies have investigated the processes underlying memory formation, the mechanisms behind memory updating and forgetting remain unclear. The endocannabinoid system has been shown to be closely involved in various memory processes such as consolidation, destabilization, and extinction. Here, we investigate the role of the endocannabinoid system in memory updating, behavioral flexibility, and forgetting. We found that the hippocampal infusion of CB1 antagonist prevented memory updating in the immediate footshock (context pre-exposure facilitation effect) and reversal learning. Also, CB1 antagonist accelerated forgetting in inhibitory avoidance. Thus, by indicating the important role played by the endocannabinoid system, our results extend current knowledge of the mechanisms underpinning memory updating and forgetting.


Differentiation of Human Induced Pluripotent Stem Cells into Mature and Myelinating Schwann Cells.
In the peripheral nervous system, Schwann cells (SCs) play a crucial role in axonal growth, metabolic support of neurons, and the production of myelin sheaths. Expansion of SCs after extraction from human or animal nerves is a long and often low-yielding process. We established a rapid cell culture method using a defined serum-free medium to differentiate human induced pluripotent stem cells (iPSCs) into SCs in only 21 days. The SC identity was characterized by expression of SRY-Box Transcription factor 10 (SOX10), S100b, glial fibrillary acidic protein (GFAP), P75, growth-associated protein 43 (GAP43), and early growth response 2 (EGR2) markers. The SC purity reached 87% as assessed by flow cytometry using the specific SOX10 marker, and 69% based on S100b expression. When SCs were cocultured with iPSC-derived motor neurons two-dimensionally or three-dimensionally (3D), they also expressed the markers of myelin MBP, MPZ, and gliomedin. Likewise, when they were seeded on the opposite side of a porous collagen sponge from motor neurons in the 3D model, they were able to migrate through it and colocalize with motor axons after 8 weeks of maturation. Moreover, they were shown by transmission electron microscopy to form myelin sheaths around motor axons. These results suggest that the use of autologous iPSC-derived SCs for clinical applications such as the repair of peripheral nerve damage, the treatment of spinal cord injuries, or for demyelinating diseases could be a valuable option. Impact Statement Peripheral nerve injuries can cause the complete paralysis of the upper or lower limbs, which considerably reduces the quality of life of patients. To repair this injury, many approaches have been developed by tissue engineering. Combining biomaterials with Schwann cells (SCs) has been shown to be an effective solution for stimulating nerve regeneration. However, the challenge faced concerns the strategy for obtaining autologous SCs to treat patients. A promising approach is to differentiate them from the patient's own cells, previously induced into pluripotent stem cells. We propose a fast culture method to generate functional SCs differentiated from induced pluripotent stem cells.


Seizure control and pharmacokinetics of antiepileptic drugs in pregnant women with epilepsy.
The main concerns associated with epilepsy during pregnancy consist of maternal and fetal risks from uncontrolled seizures, and harmful effects of the treatment on the development of the offspring. Although seizure control is maintained in the majority, worsening occurs in a fraction of childbearing women with epilepsy. As multiple factors associated with pregnancy may have a negative impact on epilepsy, a careful analysis of the situation should be performed in those who deteriorate. Emotional and behavioural influence, including insufficient sleep and treatment non-compliance, as well as physical factors, such as emesis and pelvic distortion, should receive attention. The serum concentrations of almost all antiepileptic drugs decrease during pregnancy, particularly those which are metabolised by glucuronidation. The inter-individual variability is pronounced. In highly protein-bound drugs, such as phenytoin and valproate, unbound drug is less affected than total concentrations. Lamotrigine and levetiracetam concentrations may decrease by more than 50% in the course of pregnancy; monohydroxyoxcarbazepine by up to 30-40%. Appropriate clinical follow-up tailored to individual needs and supported by therapeutic drug monitoring should be performed in pregnant women with epilepsy. Education concerning reproductive issues is an essential part of the epilepsy service to fertile women.


Transarterial chemoembolization with doxorubicin-loaded beads for inoperable or recurrent colorectal cancer.
We aimed to assess the safety and efficacy of transarterial chemoembolization (TACE) with doxorubicin-loaded CalliSpheres® beads (DEB-TACE) for the treatment of patients with inoperable or recurrent colorectal cancer (CRC). This retrospective study recruited 12 consecutive patients with histology confirmation of CRC who received DEB-TACE between August 2017 and April 2020. There were 9 male and 3 female, with a mean age 62.5 ± 14.9 (range 29-84). Patients' characteristics, medical imaging data, complications and DEB-TACE procedure were retrospectively reviewed. The disease control rate was defined as the sum of complete response, partial response and stable disease. DEB-TACE was successfully performed in all patients. All patients showed local disease control 1 month after DEB-TACE. Disease control rates were 90.9% and 70.0% at 3 and 6 months after DEB-TACE procedure, respectively. Disease-free interval was 11.0 to 81.8 months. Five patients (41.7%) received prior chemotherapy treatments. No severe complications or procedure-related deaths were observed. The median overall survival was 15.9 months, and median progression-free survival was 13.4 months. DEB-TACE is a safe and effective treatment and could be a option for patients with inoperable or recurred CRC.


Congenital isolated right radial club hand.
Congenital radial club hand (RCH) is an uncommon congenital anomaly characterized by various degrees of deficiency along the preaxial or radial side of the extremity. We present one such case of Type 4 congenital isolated RCH who presented to a tertiary care center in the Middle East.


Evolution of risk for neurologic deficit after descending and thoracoabdominal aortic repair.
Cross-clamp time has been reported to correlate with risk of neurologic deficit after thoracoabdominal aortic aneurysm repair. Introduction of cerebrospinal fluid drainage and distal aortic perfusion (adjunct) has greatly reduced the incidence of neurologic deficit. We reevaluated the effect of cross-clamp time before and after introduction of adjunct during a 13-year period. Between 1991 and 2004, we repaired 1,106 thoracic and thoracoabdominal aortic aneurysms. Four hundred one patients were female and 705 were male (median age, 67 years). Selective use of adjunct was begun in late 1992, with its routine use by 1993. Aortic cross-clamp times have increased significantly (34 seconds/year; p < 0.0001) since 1991. Despite this increase in cross-clamp time, neurologic deficit rates have declined from the first to the fourth quartile (p < 0.02). This decrease in neurologic deficit is most pronounced with the extent II thoracoabdominal aortic aneurysms (21.1% to 3.3%). The use of the adjunct increased the cross-clamp time by a mean of 12 minutes (p < 0.0001), but was associated with a significant protective effect against neurologic deficit (odds ratio = 0.4; p < 0.0002). Although other previously established risk factors remained significantly associated with neurologic deficit, cross-clamp time is no longer significant. Adjunct significantly reduced the risk of neurologic deficit, despite increasing cross-clamp time. The use of the adjunct appears to blunt the effect of the cross-clamp time and may provide the surgeon the ability to operate without being hurried. Because cross-clamp time has been effectively eliminated as a risk factor with the use of the adjunct, using this variable to construct risk models becomes irrelevant in our experience.


Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma (ESCC) remains one of the deadly cancer types. Comprehensively dissecting the molecular characterization and the heterogeneity of ESCC paves the way for developing more promising therapeutics. Expression profiles of multiple ESCC datasets were integrated. ATAC-seq and RNA-seq were combined to reveal the chromatin accessibility features. A prognosis-related subtype classifier (PrSC) was constructed, and its association with the tumor microenvironment (TME) and immunotherapy was assessed. The key gene signature was validated in clinical samples. Based on the TME heterogeneity of ESCC patients, potential subtype-specific therapeutic agents were screened. The common differentially expressed genes (cDEGs) in ESCC were identified. Up-regulated genes (HEATR1, TIMELESS, DTL, GINS1, RUVBL1, and ECT2) were found highly important in ESCC cell survival. The expression alterations of PRIM2, HPGD, NELL2, and TFAP2B were associated with chromatin accessibility changes. PrSC was a robust scoring tool that was not only associated with the prognosis of ESCC patients, but also could reflect the TME heterogeneity. TNS1high fibroblasts were associated with immune exclusion. TG-101348 and Vinorelbine were identified as potential subtype-specific therapeutic agents. Besides, the application of PrSC into two immunotherapy cohorts indicated its potential value in assessing treatment response to immunotherapy. Our study depicted the multi-dimensional characterization of ESCC, established a robust scoring tool for the prognosis assessment, highlighted the role of TNS1high fibroblasts in TME, and identified potential drugs for clinical use. A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.


Survival in a zombie apocalypse.
The Resident Evil 3 remake was in development long before the coronavirus outbreak, but it holds up a mirror to the strange times we live in today, says Jacob Aron.


First report on the isolation of Chlamydia abortus from female dromedary camels with ovarian hydrobursitis.
This study sought to isolate Chlamydia abortus (C. abortus) from camels with ovarian hydrobursitis (OVHB). To accomplish this goal, bursal tissue (n = 5) and bursal fluid (n = 6) samples were collected from 11 female dromedary camels with unilateral OVHB. A quantitative polymerase chain reaction (qPCR) was used for the preliminary detection of C. abortus in the infected samples. For the purpose of isolation, the prepared samples were inoculated into embryonated chicken eggs. Giemsa, Gimenez, and direct immunofluorescence (DIF) staining were used to detect any chlamydial inclusions in the infected yolk sacs. A second qPCR was then performed on the infected yolk sacs. The C. abortus gene was detected in 83.8% of the infected bursal tissue and bursal fluid samples. All the yolk sac smears treated with Giemsa, Gimenez, and DIF staining revealed intracytoplasmic inclusion bodies. Moreover, hemorrhagic patches, massive congestion, macerated yolk sacs, and dwarfism were observed in the infected chicken embryos. The C. abortus gene was also found in 63.6% of the infected yolk sacs. In conclusion, this is the first report of C. abortus isolation from female dromedary camels with OVHB, which represents a key step toward developing a practical vaccine and avoiding fertility problems in female camels.


An empirical evaluation of the Arizona sexual experience scale and a simple one-item screening test for assessing antipsychotic-related sexual dysfunction in outpatients with schizophrenia and schizoaffective disorder.
We examined the reliability and construct validity of the 5-Item Arizona Sexual Experience Scale (ASEX) in patients with schizophrenia or schizoaffective disorder. In addition, we assessed the performance of two 1-item screening questions to detect sexual dysfunction as defined by a cut-off scoring criteria of sexual dysfunction for the ASEX. One question was a general question about any side effects. The second question asked specifically about sexual dysfunction. Altogether 247 participants with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder provided data at a single interview. Results indicated that the ASEX has good internal consistency and construct validity for the patients with schizophrenia and schizoaffective disorder. The point-biserial correlations and logistic regression found a high degree of agreement between the one-item specific screening question for sexual dysfunction and the ASEX. Overall, sensitivity (85%), specificity (63.7%), and positive (83%) and negative (67.1%) predictive values for the specific one-item screening question were satisfactory. The single general side effect question performed poorly (sensitivity=11.3%; specificity=92.5%; positive predictive value=76%; negative predictive value=33%). The current findings demonstrate the highly acceptable psychometric properties of the ASEX in patients with schizophrenia or schizoaffective disorder. In addition, a specific one-item screening question is of clinical utility in patients with schizophrenia or schizoaffective disorder.


Terrain and its effects on fog occurrence.
Fog is a very complex phenomenon, relevant to both atmospheric physics and chemistry, contributing to the atmospheric inputs of both nutrients and pollutants to the environment. Fog occurrence is affected by numerous factors. The aim of this study is to examine the effects of terrain on fog occurrence. Namely, we studied in detail how altitude, slope and landform influence the probability of fog occurrence using the generalized additive model. In particular, we investigated how different explanatory variables might modify (deform) the trend and the seasonal component of the probability of fog occurrence. We used long-term records of daily fog occurrence measured in 1981-2017 at 56 professional meteorological stations in Romania, reflecting different environments and geographical areas. The altitude of the sites under review ranged between 13 and 2504 m above sea level, the coverage of localities at different altitudes being highly uneven. Out of the terrain variables considered, the most decisive influence was found to be altitude. We have included information on slope and landform, which refined and bettered the basic model. Our model results indicated a significant decrease in the probability of fog occurrence over the examined period. The behaviour of fog differed according to the altitude, the most profound effects being observed for ground-level fog and fog above flat terrain. The probability of fog occurrence at different altitudes varied mostly in summer and autumn, whereas it was very similar in winter.


Weight change and fracture risk in patients with diabetic kidney disease: A nationwide population-based study.
The increased risk of fracture has been associated with weight loss in patients with diabetes or chronic kidney disease. However, the relationship between weight changes over time and fracture risk in patients with diabetic kidney disease is still unknown. A total number of 78,922 patients with diabetic kidney disease, aged ≥ 40 years, were selected using the Korean National Health Insurance Service database, between 2009 and 2012. They were followed up until the end of 2018. Weight change was defined as the difference in body weight from the index year to 2 years later. Weight changes were then divided into five categories, ranging from weight loss of ≥10% to weight gain of ≥10%. Fractures were identified in 9,847 patients with diabetic kidney disease, over a median follow-up of 5.2 years. The risk of composite fracture of the vertebral, hip, or other sites increased as the weight change increased. Specifically, patients with ≥10% weight loss (hazard ratio [HR], 1.286; 95% confidence interval [CI], 1.184-1.398) and ≥10% weight gain (HR, 1.198; 95% CI, 1.080-1.330) showed a higher HR compared to those with ≤ 5% weight change after adjusting for several confounding factors. Higher HR of vertebral and hip fractures was also seen with increased weight loss or gain. In particular, patients with ≥10% weight loss showed the highest HR for hip fractures (HR, 1.738; 95% CI, 1.489-2.028). Both weight loss and weight gain increase the risk of fracture in patients with diabetic kidney disease. Therefore, patients with diabetic kidney disease who experience weight changes should be made aware of the risk of fracture.


Echographic and Doppler screening of the forearm arteries in professional volleyball players.
We evaluated nine professional volleyball players by clinical, echographic, and Doppler technique examination of the forearm and digital arteries to determine vascular damage caused by repeated trauma. The results of these tests showed that one-third of the subjects had vascular lesions in the right hand; only one of these was symptomatic. This suggests that noninvasive screening should be recommended and included in the regular medical check-ups of professional athletes in whom repeated trauma to the hand is likely, such as volleyball players.