Endoscopic projection of the gastroduodenal artery: Anatomical implications for bleeding management.
Peptic ulcers account for 50% of upper gastrointestinal bleeding incidents. Bleedings from large vessels, such as the gastroduodenal artery, are associated with increased mortality. Ulcers located on the posterior wall of the duodenum show the highest risk for erosion of the gastroduodenal artery. Endoscopic management is challenging and rebleeding rates are high due to internal and external confounding factors such as anatomical variability and gastric insufflation. We aimed to correlate macroscopic and endoscopic anatomy for assessment of implications for clinical management. The gastroduodenal artery was dissected in 10 anatomical specimens. The points of contact of the artery with the posterior wall of the duodenum were marked with needles. The endoluminal position of the needles was recorded by standardized gastroscopy and a 3-dimensional virtual reconstruction was carried out for visualization of the artery's course. The artery's proximal and distal points of contact with the duodenum were 27.2mm (range 15-30mm; SD 6.7mm) and 15mm (range 10-20mm; SD 3.5mm), respectively, from the pylorus. The gastroduodenal artery branches from the common hepatic artery within the omentum minus running adjacent to the duodenal wall to the head of the pancreas. From endoscopic perspective, the gastroduodenal artery's course was directed towards the tip of the gastroscope. Due to the peculiar extraluminal course of the gastroduodenal artery the arterial blood flow projects into the direction of the gastroscope during endoscopic intervention. Measures for bleeding control might have to be applied aboral from the bleeding site.


Pineal response types in the frog's brain under white light exposure.
Responses to white light stimulation can be recorded with electrophysiological methods at the level of (1) the pineal system (2) different diencephalic nuclei and (3) the mesencephalic tegmentum. The neurons are classified in six groups according to their discharge characteristics. As some responses present a higher complexity than the classical messages, an integration of the pineal informations during their course toward the brain is suggested in order to support phototactic behavior.


Additive-Free Radical Cascade Reaction of Oxime Esters: Synthesis of Pyrroline-Functionalized Phenanthridines.
A variety of dihydropyrrole-functionalized phenanthridines were efficiently synthesized by the metal-free, radical cascade cyclization reaction of 2-isocyanobiphenyls with γ,δ-unsaturated oxime esters. The C-N/C-C/C-C bonds were formed via the oil bath method in a one-pot procedure with broad substrate applicability. The radical process was supported by kinetic isotope effect studies and radical inhibition studies.


Synthesis and characterization of novel amphiphilic copolymer stearic acid-coupled F127 nanoparticles for nano-technology based drug delivery system.
Pluronic, F127, amphiphilic block copolymers, are used for several applications, including drug delivery systems. The critical micelle concentration (CMC) of F127 is about 0.26-0.8 wt% so that the utility of F127 in nano-technology based drug delivery system is limited since the nano-sized micelles could dissociate upon dilution. Herein, stearic acid (SA) was simply coupled to F127 between the carboxyl group of SA and the hydroxyl group of F127, which formed a novel copolymer named as SA-coupled F127, with significantly lower CMC. Above the CMC 6.9 × 10(-5)wt%, SA-coupled F127 self-assembled stable nanoparticles with Zeta potential -36 mV. Doxorubicin (DOX)-loaded nanoparticles were made, with drug loading (DL) 5.7 wt% and Zeta potential -36 to -39 mV, and the nanoparticles exhibited distinct shape with the size distribution from 20 to 50 nm. DOX-loaded nanoparticles were relatively stable and exhibited DOX dependant cytotoxicity toward MCF-7 cells in vitro. These results suggest that SA-coupled F127 potentially could be applied as a nano-technology based drug delivery method.


Neuropathic Pain Medication Use Does Not Alter Outcomes of Spinal Cord Stimulation for Lower Extremity Pain.
Spinal cord stimulation (SCS) for the treatment of lower extremity pain is believed to the result of increased activity in the descending inhibitory and decreased activity in the ascending excitatory tracts. Evidence suggests that the analgesia afforded by SCS may be altered using certain neuropathic pain medications that also modulate neurotransmitters in these sensory tracts. We hypothesize that neuropathic pain medications may alter the response to SCS therapy. One hundred and fifteen subjects undergoing SCS therapy for lower extremity pain were retrospectively examined. The pharmacologic profile, including stable use of neuropathic and opioid medications, were recorded. Three separate logistic regression models examined the odds ratio of primary outcomes; a successful SCS trial, a 50% decrease in pain or a 50% reduction in opioid use one year after implant. Neither the use of opioids or neuropathic pain medications were associated with changes in the odds of a successful SCS trial or a 50% pain reduction. A higher dose of chronic opioids use prior to a trial was associated with greater odds of having a 50% reduction in opioid use following implant. OR 1.02, 95% CI 1.01-1.02, p-value < 0.01). The use of neuropathic pain medications did not change the odds of either a successful SCS trial, or of experiencing a 50% reduction in pain at one year. The association between higher opioid doses and greater odds of a 50% reduction in opioid use may be the reflective of SCS's ability to reduce opioid reliance in chronic pain patients.


Age-related trends and reference intervals of cross-linked C-telopeptide of type I collagen and procollagen type I N-propeptide from a reference population of Sri Lankan adult women.
Refer ence values of bone turnover markers (BTMs) are determined by factors that are country-specific. In Sri Lanka, unavailability of BTM reference data has led to their non-use in management of osteoporosis. The results of this study can be used as reference data for women in Sri Lanka. This study was performed to establish age-related reference intervals for bone resorption marker; cross-linked C-telopeptide of type I collagen (CTX) and bone formation marker; procollagen type I N-propeptide (PINP) in a group of Sri Lankan adult women. Adult women (n = 347) aged 20-70 years were recruited using age-stratified random sampling technique and categorized into age groups by decades. Serum CTX and PINP concentration were measured using enzyme-linked immunosorbent assay (ELISA). The geometric mean (95% confidence interval) and 2.5th and 97.5th percentiles were calculated. ANOVA was used to compare the means between groups. Mean CTX levels were relatively low and remained unchanged between 20 and 49 years. After the age of 49 years, mean CTXconcentration elevated significantly until the age of 70 years (43%, p < 0.001). Mean PINP concentrations were not significantly different between age categories (p > 0.05). Reference intervals of CTX and PINP were based on 2.5th and 97.5th percentile values. Reference intervals of CTX for the age groups of 20-29, 30-39, 40-49, 50-59, and 60-70 years were 0.19-0.97 ng/mL, 0.18-0.95 ng/mL, 0.20-1.29 ng/mL, 0.17-2.20 ng/mL, and 0.17-2.85 ng/mL respectively. Reference intervals of PINP for the same age groups were 118-810 pg/mL, 119-772 pg/mL, 116-645 pg/mL, 108-684 pg/mL, and 108-715 pg/mL respectively. In Sri Lanka, bone turnover markers are not used in evaluating patients mainly due to lack of normative data. These values can be used as reference data for women in this age group.


Tetrazole Azasydnone (C2 N7 O2 H) And Its Salts: High-Performing Zwitterionic Energetic Materials Containing A Unique Explosophore.
This work reports the first compound containing both a tetrazole and an azasydnone ring, a unique energetic material. Several energetic salts of the tetrazole azasydnone were synthesized and characterized, leading to the creation of new secondary and primary explosives. Molecular structures are confirmed by 1 H and 13 C NMR, IR spectroscopy, and X-ray crystallographic analysis. The high heats of formation, fast detonation velocities, and straight-forward synthesis of energetic azasydnones should capture the attention of future energetics research.


Role of GPR81 in lactate-mediated reduction of adipose lipolysis.
Heavy exercise or oxygen deficit often links with higher levels of arterial lactate and lower levels of plasma free fatty acids (FFA). Treatment with lactate reduces circulating levels of FFA in vivo and lipolysis in adipose tissues in vitro. However, the underlying mechanism has remained unclear. Here we employ pharmacological and genetic approaches to show that GPR81, an orphan G-protein-coupled receptor with relatively restricted expression in the adipose tissues, functions as a receptor for lactate and can mediate an anti-lipolytic effect of lactate. GPR81 may thus function as a sensor of lactate that can modulate the FFA pool under exercise or conditions of oxygen deficit.


DeNovoGear: de novo indel and point mutation discovery and phasing.
We present DeNovoGear software for analyzing de novo mutations from familial and somatic tissue sequencing data. DeNovoGear uses likelihood-based error modeling to reduce the false positive rate of mutation discovery in exome analysis and fragment information to identify the parental origin of germ-line mutations. We used DeNovoGear on human whole-genome sequencing data to produce a set of predicted de novo insertion and/or deletion (indel) mutations with a 95% validation rate.


Clomid or nafoxidine administered to neonatal rats causes reproductive tract abnormalities.
A single injection of either Clomid or Nafoxidine in neonatal rats causes multiple abnormalities of the reproductive tract of the adult female animal. These anomalies include cystic ovaries, ovarian hypoplasia, hilus cell tumors, oviductal hyperplasia, pyometra, epithelial metaplasia, uterine cystic hyperplasia, and tumors of the uterus.


Photothermal tumor ablation in mice with repeated therapy sessions using NIR-absorbing micellar hydrogels formed in situ.
Repeated cancer treatments are common, owing to the aggressive and resistant nature of tumors. This work presents a chitosan (CS) derivative that contains self-doped polyaniline (PANI) side chains, capable of self-assembling to form micelles and then transforming into hydrogels driven by a local change in pH. Analysis results of small-angle X-ray scattering indicate that the sol-gel transition of this CS derivative may provide the mechanical integrity to maintain its spatial stability in the microenvironment of solid tumors. The micelles formed in the CS hydrogel function as nanoscaled heating sources upon exposure to near-infrared light, thereby enabling the selective killing of cancer cells in a light-treated area. Additionally, photothermal efficacy of the micellar hydrogel is evaluated using a tumor-bearing mouse model; hollow gold nanospheres (HGNs) are used for comparison. Given the ability of the micellar hydrogel to provide spatial stability within a solid tumor, which prevents its leakage from the injection site, the therapeutic efficacy of this hydrogel, as a photothermal therapeutic agent for repeated treatments, exceeds that of nanosized HGNs. Results of this study demonstrate that this in situ-formed micellar hydrogel is a highly promising modality for repeated cancer treatments, providing a clinically viable, minimally invasive phototherapeutic option for therapeutic treatment.


Tropane ethyl esters in illicit cocaine: isolation, detection, and determination of new manufacturing by-products from the clandestine purification of crude cocaine base with ethanol.
Seven ethyl homologues of known tropane esters have recently been detected as impurities in the gas chromatographic signature profiles of authentic Peruvian illicit cocaine base and hydrochloride exhibits. Peruvian cocaine base processors are now known to use ethanol for the purification of crude cocaine base. This process is referred to as the "base lavada" or "washed base" process and is a recent substitute method for the potassium permanganate oxidation purification methodology. Seven ethyl ester homologues were formed in illicit cocaine from the transesterification of known tropane methyl esters or possibly ethyl esterification of their respective tropane C-2 carboxylic acids in the presence of ethanol. Exhibits containing these compounds were subjected to gas chromatographic-mass spectrometric analyses to determine their identity and were subsequently synthesized to verify their structures. Quantitative determinations were obtained from ion-pair chromatography isolation followed by gas chromatography with flame ionization detection. Specifically, hexanoylecgonine ethyl ester, cocaethylene, cis-cinnamoylecgonine ethyl ester, trans-cinnamoylecgonine ethyl ester, 3',4',5'-trimethoxybenzoylecgonine ethyl ester, cis-3',4',5'-trimethoxycinnamoylecgonine ethyl ester, and trans-3',4',5'-trimethoxycinnamoylecgonine ethyl ester were detected and characterized. When present, these compounds were detected at levels ranging from 8.6 x 10(-4) to 9.3 x 10(-1)% relative to cocaine.


Peptide transporter TAP mediates between competing antigen sources generating distinct surface MHC class I peptide repertoires.
We recently described a category of TAP-independent peptide-epitopes that are selectively presented by cells with processing defects in the classical MHC class I (MHC-I) pathway. Here, we studied the ER-resident ceramide synthase Trh4 as a prototypic example of these neo-antigens and found that moderate inhibition of TAP permits cell surface presentation of the Trh4 peptide. The absence of this peptide from WT cells was not related to the binding or stability of the Trh4/D(b) complexes, or to the availability of MHC-I heavy chains, but rather to the limited expression of the antigen. Strongly elevated antigen levels were needed to reach comparable peptide display on WT as on TAP-deficient cells. Our data suggest that the normal influx of TAP-transported peptides in the ER during routine processing creates an efficient barrier for peptides from alternative processing routes. Impairment of TAP function, as commonly found in cancers and virus-infected cells, lowers this resistance allowing for MHC-I presentation of other peptide sources.


Anomalous drainage of the right superior vena cava into the left atrium as an isolated anomaly. Rare case report.
A case of cyanotic congenital heart disease with left ventricular hypertrophy is described. Cardiac catheterization showed a right superior vena cava draining into the left atrium without other cardiovascular abnormality. This is the fifth case of this rare congenital anomaly described in the literature and the first one reported in a male. The patient was 7-months-old when diagnosed. Despite the important right-to-left shunt, after a follow-up of 2 years, growth and development are normal.


A model of the upper extremity for simulating musculoskeletal surgery and analyzing neuromuscular control.
Biomechanical models of the musculoskeletal system are frequently used to study neuromuscular control and simulate surgical procedures. To be broadly applicable, a model must be accessible to users, provide accurate representations of muscles and joints, and capture important interactions between joints. We have developed a model of the upper extremity that includes 15 degrees of freedom representing the shoulder, elbow, forearm, wrist, thumb, and index finger, and 50 muscle compartments crossing these joints. The kinematics of each joint and the force-generating parameters for each muscle were derived from experimental data. The model estimates the muscle-tendon lengths and moment arms for each of the muscles over a wide range of postures. Given a pattern of muscle activations, the model also estimates muscle forces and joint moments. The moment arms and maximum moment-generating capacity of each muscle group (e.g., elbow flexors) were compared to experimental data to assess the accuracy of the model. These comparisons showed that moment arms and joint moments estimated using the model captured important features of upper extremity geometry and mechanics. The model also revealed coupling between joints, such as increased passive finger flexion moment with wrist extension. The computer model is available to researchers at http://nmbl.stanford.edu.


Application of a mixture DOE for the prediction of formulation critical temperatures during lyophilisation process optimisation.
During lyophilisation cycle design, primary drying parameters (chamber pressure and shelf temperature) are adjusted to maximize the sublimation rate and prevent cake collapse, by maintaining the product continuously below its critical temperatures. The objective of this study was to employ mixture design of experiments to generate empirical models capable of predicting glass transition of the maximally freeze concentrated solution (Tg') and collapse temperature (Tc) of amorphous protein (BSA and IgG1) formulations. Additionally, the models developed aid the design of high concentration protein formulations with maximised critical temperatures to obtain shorter and more cost-effective lyophilisation cycles. Formulations contain sucrose as cryo/lyo-protectant and arginine/arginine-HCl as multifunctional excipient (e.g. solubility enhancer, viscosity and aggregation suppressor). The impact of formulation components at varied ratios on critical temperatures was evaluated; the amorphous excipients decrease critical temperatures, on the contrary, the protein increases critical temperatures. The robustness of the empirical models generated with BSA formulations was verified with BSA and IgG1 formulations. The models showed greater accuracy in predicting Tg' than the Fox-Flory equation. For the first time, empirical models are reported to predict both critical temperatures. Finally, unconventional collapse events observed for formulations with and without arginine/arginine-HCl at different protein concentrations are also discussed.


RNA-seq analysis of Macrobrachium rosenbergii hepatopancreas in response to Vibrio parahaemolyticus infection.
The Malaysian giant freshwater prawn, Macrobrachium rosenbergii, is an economically important crustacean worldwide. However, production of this prawn is facing a serious threat from Vibriosis disease caused by Vibrio species such as Vibrio parahaemolyticus. Unfortunately, the mechanisms involved in the immune response of this species to bacterial infection are not fully understood. We therefore used a high-throughput deep sequencing technology to investigate the transcriptome and comparative expression profiles of the hepatopancreas from this freshwater prawn infected with V. parahaemolyticus to gain an increased understanding of the molecular mechanisms underlying the species' immune response to this pathogenic bacteria. A total of 59,122,940 raw reads were obtained from the control group, and 58,385,094 reads from the Vibrio-infected group. Via de novo assembly by Trinity assembler, 59,050 control unigenes and 73,946 Vibrio-infected group unigenes were obtained. By clustering unigenes from both libraries, a total of 64,411 standard unigenes were produced. The standard unigenes were annotated against the NCBI non-redundant, Swiss-Prot, Kyoto Encyclopaedia of Genes and Genome pathway (KEGG) and Orthologous Groups of Proteins (COG) databases, with 19,799 (30.73%), 16,832 (26.13%), 14,706 (22.83%) and 7,856 (12.19%) hits respectively, giving a final total of 22,455 significant hits (34.86% of all unigenes). A Gene Ontology (GO) analysis search using the Blast2GO program resulted in 6,007 unigenes (9.32%) being categorized into 55 functional groups. A differential gene expression analysis produced a total of 14,569 unigenes aberrantly expressed, with 11,446 unigenes significantly up-regulated and 3,103 unigenes significantly down-regulated. The differentially expressed immune genes fall under various processes of the animal immune system. This study provided an insight into the antibacterial mechanism in M. rosenbergii and the role of differentially expressed immune genes in response to V. parahaemolyticus infection. Furthermore, this study has generated an abundant list of transcript from M.rosenbergii which will provide a fundamental basis for future genomics research in this field.


Use of methenamine hippurate in male infertility.
In sperm-freezing for infertility patients with low sperm counts, we found that semen containing high numbers of white blood cells, greater than 15 to 20 per high-power field, was both poor in quality and difficult to freeze. In examining these patients carefully, we found that many had smoldering prostatitis and some an overt history of prostatitis. We treated them with methenamine hippurate using various methods and found that by decreasing the white blood cell count in their semen, we could frequently improve the semen quality, particularly sperm motility, also achieve pregnancies in some cases.


Angiography after paint-gun injury of the hand: a case report.
Because the severity and extent of vascular damage may determine the surgical treatment, angiography may be an important preoperative investigation of injection injuries. An example of a paint-gun injury to the hand, in which serious vascular damage was confirmed by angiography, is described.


Insect fat body phosphorylase kinase is Ca2+-independent and acts even at 0 degrees C.
Fat body glycogen phosphorylase in some overwintering insects is known to be activated by cold and, therefore, this enzyme acts as a key enzyme that regulates the production of glycerol or trehalose from glycogen during winter. In this paper we report the mechanism of phosphorylase activation by cold: the major phosphorylase kinase (EC 220.127.116.11) of fat body is bound to glycogen and functions at 0 degrees C, whereas phosphorylase phosphatase does not; thus this may cause a slow but continuous accumulation of the active form of phosphorylase in the cold.


Electrical callus and callus formation by electret.
The callus formed by passing an electric current through bone is called electrodynamic callus. The amount of electrical current determines the quality of the callus (osseous, cartilagenous, or fibrous). Callus forms first at the negative pole and grows toward the positive pole. The callus formed by placing a teflon film electret near the surface of bone is called electrostatic callus. The amount of this callus is larger when the bone is wrapped by the electret film than when the film is laid over the bone.


[The photon therapy of subfoveal choroidal neovascularization in age-dependent macular degeneration. The results of a prospective study in 40 patients].
To determine the effect of external beam radiotherapy on subfoveal choroidal neovascularization in age-related macular degeneration. Between September 1995 and July 1996, 40 patients (9 males and 31 females; mean age 74 years, range 61 to 83 years) were included in a prospective study. Eight patients had classic, well-defined neovascularisations, 32 patients had occult lesions. Complete ophthalmic investigations included visual acuity contrast sensitivity as well as fluorescein and indocyanine green angiographic examinations prior to treatment and 1, 3, 6, and 12 months after radiotherapy. External beam radiotherapy (8-MV photons) was delivered with a total dose of 14.4 Gy in 8 fractions of 1.8 Gy per day (Figures 1 and 2). The field size averaged 5.5 x 4.5 cm. No treatment related morbidity during or after treatment was obtained. After 6 months follow-up the visual acuity was improved in 2 (5%) patients and maintained at pretreatment level in 17 (42%) patients. However, 12 months post treatment a stable situation was found in 6 (15%) patients and a decrease in visual acuity in 34 (85%) patients (Table 1). The central visual fields deteriorated significantly from 16.5 decibel (dB) to 12.4 dB. The enlargement of exudates and neovascular membranes increased 5- to 7-fold. At 12 months after treatment, 3 (7.5%) patients stated that they had improved vision subjectively, 12 (30%) patients had no change and 25 (62.5%) patients suffered from subjective decrease in visual acuity. Using a total dose of 14.4 Gy/1.8 Gy no difference concerning visual acuity and exudative changes in comparison to the natural history on age-related macular degeneration was obtained after 12 months. However, the results of multicenter studies are to be awaited.


Experimental study on anisotropic unloading mechanical behavior of bedded sandstone.
Sandstone is a kind of bedded rock mass commonly used in engineering. The deformation and strength of bedded sandstone impose some problems during excavation. In this study, triaxial unloading tests were conducted on rock specimens (considering seven different bedding angles (β)). The results revealed the following key points: (1) At a constant confining pressure, the elastic modulus was gradually increasing when the bedding angle increased. Furthermore, after initial decreasing, the deformation modulus was increased and had a U-shaped distribution. (2) During the unloading of the axial compression, the rate of axial strain variations was initially increased and then decreased while the bedding angle increased (it has exhibited an inverted U-shaped distribution). However, the peak strength, cohesion, and angle of internal friction of rock specimens showed an initial decreasing and then increasing trend. (3) During the loading and unloading stages, the confining pressure reduces the anisotropy of bedded rock masses. (4) In the triaxial unloading test, the failure of rock specimens can be classified into four modes. When there was a large intersection angle between the bedding plane and the unloading direction, failure developed at the bedding planes.


Inhalation exposure to ethylene induces eosinophilic rhinitis and nasal epithelial remodeling in Fischer 344 rats.
This study investigated the time- and concentration-dependent effects of inhaled ethylene on eosinophilic rhinitis and nasal epithelial remodeling in Fisher 344 rats exposed to 0, 10, 50, 300, or 10,000 ppm ethylene, 6 h/day, 5 days/week for up to 4 weeks. Morphometric quantitation of eosinophilic inflammation and mucous cell metaplasia/hyperplasia (MCM) and nasal mucosal gene expression were evaluated at anatomic sites previously shown to undergo ethylene-induced epithelial remodeling. Serum levels of total IgE, IgG1 and IgG2a were measured to determine if ethylene exposure increased the expression of Th2-associated (IgE and IgG1) relative to Th1-associated (IgG2a) antibody isotypes. Rats exposed to 0 or 10,000 ppm for 1, 3, 5, 10, or 20 days were analyzed to assess the temporal pattern of ethylene-induced alterations in nasal epithelial cell proliferation, morphology and gene expression. Rats exposed to 0, 10, 50, 300, and 10,000 ppm ethylene for 20 days were analyzed to assess concentration-dependent effects on lesion development. Additional rats exposed 4 weeks to 0, 300, or 10,000 ppm ethylene were held for 13 weeks post-exposure to examine the persistence of ethylene-induced mucosal alterations. The data indicate that cell death and reparative cell proliferation were not a part of the pathogenesis of ethylene-induced nasal lesions. Enhanced gene expression of Th2 cytokines (e.g., IL-5, IL-13) and chitinase (YM1/2) in the nasal mucosa was much greater than that of Th1 cytokines (e.g., IFNγ) after ethylene exposure. A significant increase in MCM was measured after 5 days of exposure to 10,000 ppm ethylene and after 20 days of exposure 10 ppm ethylene. Ethylene-induced MCM was reversible after cessation of exposure. No increase in total serum IgE, IgG1 or IgG2a was measured in any ethylene-exposed group. These data do not support involvement of an immune-mediated allergic mechanism in the pathogenesis of ethylene-induced nasal lesions in rats. Repeated inhalation of ethylene can induce a local Th2-mediated response in the nasal mucosa of rats, however the mechanisms which induce nasal inflammatory and epithelial responses are yet to be determined.


Explaining frailty by lifestyle.
To determine whether the effects of lifestyle factors on frailty can be adequately addressed by asking a single self-report question. Cross-sectional study. A sample of Dutch citizens completed the web-based questionnaire "Seniorenbarometer". 610 persons aged 50 years and older. Seven lifestyle factors were assessed: smoking, use of alcohol, intake of vegetables, intake of fruit, having breakfast, exercise, and teeth brushing. The single self-report question of lifestyle was: "Overall, how healthy would you say your lifestyle is?" Frailty was measured by the Tilburg Frailty Indicator. Age was positively associated with a healthy lifestyle (less smoking, more intake of vegetables, fruit and eating breakfast). The lifestyle factors did not improve the prediction of total, physical, psychological, and social frailty, after controlling for the single self-report question. Our study suggests that one general self-report lifestyle question, rather than a list of specific lifestyle factors, suffices for predicting frailty.


[Personalized brain revascularization: computer modeling of the reconstruction zone for carotid endarterectomy].
To develop a technique of computer modeling of hemodynamics before conventional CEE. Classical CEE is performed according to conventional patch technique. Duplex parameters of stenosis and blood flow velocity in the carotid arteries were analyzed by using of a linear transducer 7-7.5 MG (Acuson 128XP scanner, Acuson, USA). Multispiral computed tomography with angiography and subsequent processing of data using the Clear canvas software were performed to visualize the main geometric characteristics of the carotid arteries and features of atherosclerotic plaque. Blood flow hemodynamics is essential in the occurrence of postoperative restenosis. Therefore, computer simulation of blood flow using CFD (Computational Fluid Dynamics) methods based on particular patient's data makes it possible to assess localization of zones with high risk of restenosis. CFD approach implies construction of blood flow parameters at absolutely every point of the vessel considering geometric shape of the vessel and flow characteristics at the entrance and exit from the vessel. Pressure curves at the inlet and outlet are constructed using blood flow velocity curves. Pressure curves are subsequently used in the CFD model. The result of blood flow CFD modeling is non-stationary three-dimensional fields of pressure and velocity in the investigated area. Visual analysis of blood flow dynamics in these fields makes it possible to judge possible problem areas along the blood flow and on the inner wall of the vessel. Patch technique of classical CEE is characterized by great risk of parietal thrombosis and hyperproliferation of neointima that explains more frequent development of restenosis. Computer modeling is valuable to consider some important technical aspects in implementation of various surgical techniques for carotid artery reconstruction. This result demonstrates an importance of achieving the optimal ratio of the diameter of common, internal and external carotid arteries. Modification of patch based on computer simulation is required for these purposes.


Long non-coding RNA SNHG20 promotes non-small cell lung cancer cell proliferation and migration by epigenetically silencing of P21 expression.
Mounting evidence demonstrates that long non-coding RNAs (lncRNAs) are novel transcripts governing multiple biological processes, and their dysregulation is involved in the development and progression of multiple types of cancers. Small Nucleolar RNA Host Gene 20 (SNHG20) is a 2183 bp lncRNA, and its overexpression predicts poor prognosis in colorectal cancer and hepatocellular carcinoma. However, the clinical relevance of SNHG20 and its molecular mechanisms affecting cancer cell phenotype have not been documented. Here, we found that SNHG20 was upregulated in non-small cell lung cancer (NSCLC) tissues compared with normal samples. Higher SNHG20 expression was significantly associated with advanced tumor, lymph node and metastases (TNM) stage and tumor size, as well as poorer overall survival. Moreover, knockdown of SNHG20 repressed NSCLC cell proliferation, migration and induced cell apoptosis. Mechanistic investigations revealed that SNHG20 could interact with EZH2 (enhancer of zeste homolog 2), thereby repressing P21 expression. Furthermore, rescue experiments indicated that SNHG20 functioned as an oncogene partly via repressing p21 in NSCLC cells. Taken together, our findings demonstrate that SNHG20 is a new candidate for use in NSCLC diagnosis, prognosis and therapy.


Production of extracellular enzymes and aflatoxins in solid substrate fermentation with aflatoxigenicAspergillus spp.
AflatoxigenicAspergillus flavus andAspergillus parasiticus were subjected to solid substrate fermentation process for 6 days to determine the formation of aflatoxins and production of extracellular enzymes (amyloglucosidase, cellulase, invertase and proteinase). Both organisms produced enzymes which generally increased with fermentation.Aspergillus flavus produced four enzymes whereasA. parasiticus produced three with no proteinase activity.Aspergillus parasiticus produced aflatoxins B1, B2 and G1 but no G2 andA. flavus produced aflatoxins B1 and B2. Invertase showed the highest activity withA. parasiticus and that corresponded with the highest total toxin produced. The enzyme activities were higher withA. parasiticus thanA. flavus although total toxins produced byA. parasiticus were lower than total toxins produced byA. flavus under the same environmental conditions.


Effects of single versus combinatorial treatment strategies on beta II-tubulin gene expression in axotomized hamster rubrospinal motoneurons.
betaII-tubulin, a regeneration-associated gene, is upregulated in injured peripheral neurons, but significantly less so in injured central neurons. Using a hamster dorsal spinal cord injury (SCI), the ability of single versus combinatorial treatment strategies to alter betaII-tubulin mRNA expression in rubrospinal motoneurons (RSMN) was examined. We have shown that systemic testosterone propionate (TP) treatment in combination with peripheral nerve grafting into a SCI site produces a peripheral-like pattern of betaII-tubulin mRNA expression in injured RSMN. In the present study, selected single- and combinatorial-therapy strategies were tested for their ability to promote a sustained upregulation of betaII-tubulin mRNA levels in injured RSMN. Single treatments of olfactory ensheathing cells (OEC), brain-derived neurotrophic factor (BDNF), or Schwann cells (SC) vs combinatorial treatments (SC+TP, OEC+TP, and OEC+BDNF) were administered to hamsters following a dorsal SCI. Quantitative in situ hybridization in conjunction with a betaII-tubulin cDNA probe was accomplished. All of the single-therapy treatments tested were able to prevent the downregulation of betaII-tubulin mRNA that occurred a week after injury alone, but only BDNF maintained high levels of betaII-tubulin mRNA. In contrast, all combinatorial treatments tested maintained the upregulation of betaII-tubulin mRNA expression in injured RSMN 1 week post-SCI. Targeting both intrinsic and extrinsic components of CNS injury can re-program elements of the molecular response of injured central motoneurons.


Penetrating head & neck trauma - Epidemiology and injury characteristics in terror-related violence, interpersonal violence and deliberate self-harm at a level 1 trauma centre.
Penetrating trauma to the head and neck presents specific clinical challenges. Aetiologies include interpersonal violence, deliberate self-harm and terror-related violence. King's College Hospital is a Major Trauma Centre serving inner-city London boroughs with a high incidence of knife and gun crime. It also received victims of the terrorist attack at London Bridge in June 2017. Data was collected prospectively on all patients presenting with penetrating trauma to the head and neck over a one-year period (August 2016-July 2017). Overall figures for penetrating trauma are the highest since comparable records began with 478 cases (2016/17) compared with 172 (2010/11). Most patients had injuries resulting from interpersonal violence (83%); a group consisting mostly in males (88%) under the age of 30 (69%). The sole fatality among all patients was a result of repeat deliberate self-harm. Terror-related violence victims were equally gender split and older; all patients in this group required surgical intervention and had longer lengths of stay (16.3 days) compared with interpersonal violence (6.3 days) and deliberate self-harm (3 days). Violent crime is increasing. Overall penetrating injury has more than doubled in 6 years. The injury characteristics observed are distinct depending on the assailants and motives. Head and neck trauma requires a multidisciplinary approach, with an understanding of the care needs of patients. Interpersonal violence is the most common aetiology and as such efforts to tackle rising violent crime must involve police and the community. In addition, terror-related violence is evolving in the United Kingdom and globally, and as such healthcare professionals must understand differences in aetiologies to promote optimal patient care.


Independent regulation of basal neurotransmitter release efficacy by variable Ca²+ influx and bouton size at small central synapses.
The efficacy of action potential evoked neurotransmitter release varies widely even among synapses supplied by the same axon, and the number of release-ready vesicles at each synapse is a major determinant of this heterogeneity. Here we identify a second, equally important, mechanism for release heterogeneity at small hippocampal synapses, the inter-synaptic variation of the exocytosis probability of release-ready vesicles. Using concurrent measurements of vesicular pool sizes, vesicular exocytosis rates, and presynaptic Ca²⁺ dynamics, in the same small hippocampal boutons, we show that the average fusion probability of release-ready vesicles varies among synapses supplied by the same axon with the size of the spike-evoked Ca²⁺ concentration transient. We further show that synapses with a high vesicular release probability exhibit a lower Ca²⁺ cooperativity, arguing that this is a direct consequence of increased Ca²⁺ influx at the active zone. We conclude that variability of neurotransmitter release under basal conditions at small central synapses is accounted for not only by the number of release-ready vesicles, but also by their fusion probabilities, which are set independently of bouton size by variable spike-evoked presynaptic Ca²⁺ influx.


Kinematic alignment versus mechanical alignment in primary total knee arthroplasty: an updated meta-analysis of randomized controlled trials.
The purpose of this study was to perform an updated meta-analysis to compare the outcomes of kinematic alignment (KA) and mechanical alignment (MA) in patients undergoing total knee arthroplasty. PubMed, EMBASE, Web of Science, Google Scholar, and the Cochrane Library were systematically searched. Eligible randomized controlled trials regarding the clinical outcomes of patients undergoing total knee arthroplasty with KA and MA were included for the analysis. A total of 1112 participants were included in this study, including 559 participants with KA and 553 patients with MA. This study revealed that the Western Ontario and McMaster Universities Osteoarthritis Index, Knee Society Score (knee and combined), and knee flexion range were better in the patients with kinematic alignment than in the mechanical alignment. In terms of radiological results, the femoral knee angle, mechanical medial proximal tibial angle, and joint line orientation angle were significantly different between the two techniques. Perioperatively, the walk distance before discharge was longer in the KA group than in the MA group. In contrast, other functional outcomes, radiological results, perioperative outcomes, and postoperative complication rates were similar in both the kinematic and mechanical alignment groups. The KA technique achieved better functional outcomes than the mechanical technique in terms of KSS (knee and combined), WOMAC scores, and knee flexion range. PROSPERO trial registration number CRD42021264519. Date registration: July 28, 2021.


Management of patients with severe, coexistent coronary artery and peripheral vascular disease.
The coexistence of severe coronary artery and peripheral vascular lesions is not uncommon. Although diagnostic and sequential therapeutic techniques are standardized, the priority of surgical treatment is unresolved. Eight cases are reported in which simultaneous surgical correction of coronary atherosclerosis and carotid atherosclerosis, abdominal aortic aneurysm, or aortoiliac atherosclerosis was accomplished with success. Two additional cases demonstrate the complications which can occur when coexistent lesions are not corrected simultaneously. The surgical techniques employed are discussed. Because of these results, a further clinical trial seems warranted.


Papillary carcinoma of the thyroid and familial polyposis coli.
A 22-year-old white woman in whom multicentric papillary carcinoma of the thyroid developed two years after prophylactic colectomy for intestinal polyposis is reported. This association has been observed by others. Patients with familial polyposis coli are at risk for a variety of malignancies other than colonic, and careful life-long surveillance is necessary.


Sodium dependence of neutral amino acid uptake into rabbit ileum.
Alanine uses two mediated pathways to enter the rabbit ileal mucosa. Present results suggest that one of them (Km = 4.1 mM) is fully dependent on sodium in the mucosal medium, while the other (Km = 91 mM) is sodium-independent. Similar results are obtained for methionine and serine. Reinterpretation of previous alanine/sodium coupling coefficients suggests that two sodium ions per alanine molecule are transported via the high affinity system.


Peripheral arterial occlusive disease: prognostic value of signs, symptoms, and the ankle-brachial pressure index.
To determine whether different levels of the ankle-brachial pressure index (ABPI) are associated with an increased risk for progressive limb ischemia, nonfatal and fatal cardiovascular events. To investigate the prognostic value of signs and symptoms associated with peripheral arterial occlusive disease (PAOD). Prospective follow-up study. Eighteen general practice centers in the Netherlands. Three thousand six hundred forty-nine participants (53% female) with a mean age of 59 years (range: 40-78 years). Progressive limb ischemia, cardiovascular morbidity and mortality. At baseline, 458 participants had PAOD, defined as an ABPI < 0.95. Among these, 148 (32.2%) had an ABPI < 0.70. Cox proportional hazards models showed that after a mean follow-up period of 7.2 years, PAOD patients with an ABPI < 0.70 were at higher risk for cardiovascular death, compared with participants with a moderately reduced ABPI (< 0.95 - > or = 0.70): HR 2.3 versus 1.2. Older age, complaints of intermittent claudication, abnormal pedal pulses, elevated blood pressure, and coexisting cardiovascular disease at baseline were also significant independent prognostic factors for one or more of the adverse outcome events in these patients. The ABPI is inversely associated with cardiovascular mortality in PAOD patients. A low ABPI is an independent predictor for cardiovascular mortality in PAOD patients.


Efficacy of hydrogastric sonography and spiral Computed Tomography in staging of gastric carcinoma--a comparative study.
Accurate preoperative diagnosis and staging of patients with gastric cancer is essential for optimal treatment. The standard of care for staging gastric carcinoma is helical CT. This study was conducted to compare the efficacy of hydrogastric sonography (HGS) with that of helical CT in the staging of patients with gastric carcinoma. A total of 42 consecutive patients (29 men and 13 women) diagnosed with gastric carcinoma after endoscopy and biopsy were staged on the basis of TNM classification, preoperatively with HGS and helical CT and postoperatively with histopathologic examination (HPE). The findings of HGS and helical CT were compared with those on HPE with respect to TNM stage. Regarding T stage, the accuracy of HGS was 78.6% (kappa = 0.68) and that of helical CT was 66.7% (kappa = 0.48). In evaluating the nodal status, the accuracy of HGS was 66.7% (kappa = 0.52) and that of helical CT was 54.6% (kappa = 0.39). Regarding distant metastases, accuracy was the same with HGS and helical CT (accuracy 95.2%, kappa = 0.89). When compared with HPE, HGS was found to be more accurate than helical CT for assessment of T and N staging. Sonographic and helical CT were equally accurate for the assessment of M stage.


Epidemiology of invasive mold infections in lung transplant recipients.
Invasive mold infections (IMIs) are a major source of morbidity and mortality among lung transplant recipients (LTRs), yet information regarding the epidemiology of IMI in this population is limited. From 2001 to 2006, multicenter prospective surveillance for IMIs among LTR was conducted by the Transplant-Associated Infection Surveillance Network. The epidemiology of IMI among all LTRs in the cohort is reported. Twelve percent (143/1173) of LTRs under surveillance at 15 US centers developed IMI infections. The 12-month cumulative incidence of IMIs was 5.5%; 3-month all-cause mortality was 21.7%. Aspergillus caused the majority (72.7%)of IMIs; non-Aspergillus infections (39, 27.3%) included Scedosporium (5, 3.5%), mucormycosis (3, 2.1%) and "unspecified" or "other" mold infections (31, 21.7%). Late-onset IMI was common: 52% occurred within 1 year posttransplant (median 11 months, range 0-162 months). IMIs are common late-onset complications with substantial mortality in LTRs. LTRs should be monitored for late-onset IMIs and prophylactic agents should be optimized based on likely pathogen.


YTHDF2/m6 A/NF-κB axis controls anti-tumor immunity by regulating intratumoral Tregs.
N6 -methyladenosine (m6 A) in messenger RNA (mRNA) regulates immune cells in homeostasis and in response to infection and inflammation. The function of the m6 A reader YTHDF2 in the tumor microenvironment (TME) in these contexts has not been explored. We discovered that the loss of YTHDF2 in regulatory T (Treg) cells reduces tumor growth in mice. Deletion of Ythdf2 in Tregs does not affect peripheral immune homeostasis but leads to increased apoptosis and impaired suppressive function of Treg cells in the TME. Elevated tumor necrosis factor (TNF) signaling in the TME promotes YTHDF2 expression, which in turn regulates NF-κB signaling by accelerating the degradation of m6 A-modified transcripts that encode NF-κB-negative regulators. This TME-specific regulation of Treg by YTHDF2 points to YTHDF2 as a potential target for anti-cancer immunotherapy, where intratumoral Treg cells can be targeted to enhance anti-tumor immune response while avoiding Treg cells in the periphery to minimize undesired inflammations.


Vitamin E increases biomarkers of estrogen stimulation when taken with tamoxifen.
Vitamin E (alpha-tocopherol acetate, AT) diminishes the antiproliferative effect of tamoxifen on breast cancer cells in vitro. A prospective study of seven women taking tamoxifen for adjuvant therapy of breast cancer. Four who were already taking AT supplements had random core biopsies of the normal breast and again 30 days after discontinuing AT. Three who were not on AT had biopsies before and after adding AT 400 mg for 30 days. Biopsies were stained for estrogen receptor (ER) and the mitogen-activated protein kinase p-ERK. Tissue extracts were assayed for p-ERK by enzyme-linked immunosorbent assay. Serum levels of alpha-tocopherol and tamoxifen were measured. Five out of seven patients had lower tamoxifen levels while taking AT, four of these went to subtherapeutic levels. Biopsies showed 23% of ductal cells were ER positive when patients were off AT and 70% on AT (P = 0.02). P-ERK staining was 21% off AT and 82% on AT. Five of seven patients had significantly higher tissue p-ERK when on AT. Biomarkers of estrogen-stimulation (ER, progesterone receptor, and p-ERK) were higher in breast biopsies of women taking vitamin E supplements while taking tamoxifen. Findings suggest that vitamin E supplements may interfere with the therapeutic effects of tamoxifen.


Understanding allosteric interactions in hMLKL protein that modulate necroptosis and its inhibition.
Mixed Lineage Kinase domain-Like (MLKL), a key player in necroptosis, is a multi-domain protein with an N-terminal 4 helical bundle (4HB) and a pseudokinase domain (PsK) connected by brace helices. Phosphorylation of PsK domain of MLKL is a key step towards oligomerization of 4HB domain that causes cell death. Necrosulfonamide (NSA) binds to the 4HB domain of MLKL to inhibit necroptosis. To understand the molecular details of MLKL function and it's inhibition, we have performed a molecular dynamic study on hMLKL protein in apo, phosphorylated and NSA-bound states for a total 3 μs simulation time. Our simulations show increased inter-domain flexibility, increased rigidification of the activation loop and increased alpha helical content in the brace helix region revealing a form of monomeric hMLKL necessary for oligomerization upon phosphorylation as compared to apo state. NSA binding disrupts this activated form and causes two main effects on hMLKL conformation: (1) locking of the relative orientation of 4HB and PsK domains by the formation of several new interactions and (2) prevention of key 4HB residues to participate in cross-linking for oligomer formation. This new understanding of the effect of hMLKL conformations on phosphorylation and NSA binding suggest new avenues for designing effective allosteric inhibitors of hMLKL.


[Orbito-zygomatic approach for removal of tumors of the skull base].
To evaluate the advantages and indications of orbito-zygomatic approach for removal of tumors of the skull base. Fifteen patients with tumors of the skull base were operated on using obito-zygomatic approach. The advantages and indications of the approach were evaluated. In 7 cases of meningioma, total removal of the tumor was achieved in 6 cases, and subtotal removal in 1. In 4 cases of craniopharyngioma, the tumor were totally removed in 3 cases, and subtotally removed in 1. The tumor were totally removed in 2 cases of trigerminal neurilemoma and 1 case of germinoma. There was one operative death. All patients recovered except 3 who had minor extraocular parasis. This approach ensures additional space, and less cerebral retraction for easy access to skull base tumor, especially the large neoplasm of middle cranial base with or without orbital or posterior cranial base extension.


Aetiology of viral hepatitis among jaundiced patients presenting to a tertiary hospital in Ghana.
Viral hepatitis continues to play significant role in causing morbidity and mortality in sub-Saharan Africa. Apart from the few population based studies available, not many have investigated the burden of these viruses in jaundiced patients. Among the few studies, hepatitis E is the least studied among jaundiced patients. This study was aimed at describing the frequency, distribution and risk of the different hepatitis viruses among jaundiced patients reporting to the second largest teaching hospital in Ghana. From November, 2015 to April, 2016, a cross-sectional study was conducted among jaundiced patients attending the Komfo Anokye Teaching Hospital. Between 3-5 ml of blood was collected from each patient and screened for viral hepatitis agents using both serologic and molecular-based assays. In the 155 patients recruited, hepatitis B was the most prevalent [54.2% (95% CI = 46.0%-62.2%)] followed by hepatitis E [32.9% (95% CI = 25.6-40.9%)]. Most cases of hepatitis E occurred as co-infections with hepatitis B (18%), with the predominant clinical feature being hepatocellular carcinoma. Risk factor variable analysis showed middle and older aged individuals were more at risk of hepatitis B exposure whereas younger age groups (<18 years) were more at risk of hepatitis E virus infection. Hepatitis viruses are still important in the viral aetiology of jaundice in Ghana. Hepatitis B and hepatitis E co-infections could play significant roles in causing severe disease. A more aggressive approach needs to be adopted in order to reduce the morbidity and mortality associated with hepatitis causing viruses in Ghana and other developing countries.


The Aged Heart.
As the US populations ages, emergency medicine providers will require increased understanding of and expertise in the care of older adults presenting to the emergency department. No more is this evident than within the domain of cardiovascular emergency care. Cardiovascular emergencies and complications related to an aging cardiovascular system are some of the most common reasons this patient populations presents for emergency evaluation. This article provides guidance on the nuances of evaluation and treatment associated with these diseases in the older adult population.


Inhibition of Shewanella spp. growth by Syzygium australe and Syzygium luehmannii extracts: natural methods for the prevention of fish spoilage.
Syzygium australe and Syzygium luehmannii fruit and leaf were investigated for their ability to inhibit Shewanella spp. growth. Extracts of both Syzygium spp. displayed potent growth inhibitory properties against all Shewanella spp. tested in disc diffusion and liquid diffusion assays. In general, S. australe extracts were more potent inhibitors of Shewanella spp. growth, and the fruit extracts were generally better than the corresponding leaf extracts. The methanolic S. australe fruit extract was a particularly potent inhibitor of all Shewanella spp. growth, with MIC values as low as 87 µg/mL. The aqueous and ethyl acetate S. australe fruit extracts were similarly potent inhibitors of Shewanella spp. growth, albeit with slightly higher MIC values. Several other Syzygium spp. extracts also were potent bacterial growth inhibitors, albeit with MIC values generally >1000 µg/mL. The most potent S. australe fruit extracts were nontoxic in the Artemia franciscana bioassay, with LC50 values substantially >1000 µg/mL. The potent bacterial growth inhibitory activity and lack of toxicity of the S. australe fruit extracts indicate their potential as natural fish and seafood preservatives.


An Integrated Population Pharmacokinetic Analysis to Characterize Levonorgestrel Pharmacokinetics After Different Administration Routes.
To compare the pharmacokinetics (PK) of the progestin levonorgestrel for various routes of administration, an integrated population PK analysis was performed. This analysis integrated data from 10 clinical pharmacology studies and resulted in a single, comprehensive population PK model (and its applications) describing the PK of levonorgestrel and its variability for 6 levonorgestrel-containing contraceptives: 3 intrauterine systems (IUSs; levonorgestrel [LNG]-IUS 20 [Mirena® ], LNG-IUS 12 [Kyleena® ], and LNG-IUS 8 [Jaydess® /Skyla® ]); 2 oral contraceptives (the progestin-only pill [Microlut® /Norgeston® ] and the combined oral contraceptive [Miranova® ]); and a subdermal implant (Jadelle® ). The levonorgestrel-containing contraceptives administered orally or as an implant act mainly via their systemic (unbound) levonorgestrel exposure, whereas levonorgestrel administered via an IUS is released directly into the uterine cavity, resulting in lower systemic levonorgestrel concentrations. The integrated population PK analysis revealed that the combined oral contraceptive led to the highest levonorgestrel exposure, followed by the progestin-only pill and the implant, which led to similar levonorgestrel exposure, and the IUSs, which led to the lowest levonorgestrel exposure (in decreasing order: LNG-IUS 20, LNG-IUS 12, and LNG-IUS 8). The difference was even more distinct at the end of the indicated duration of use of 3 years (LNG-IUS 8) and 5 years (LNG-IUS 20 and LNG-IUS 12). Comparing the 3 IUSs and the implant, in vivo release rates were highest for the implant, followed by LNG-IUS 20, then LNG-IUS 12, and were lowest for LNG-IUS 8. This is in line with the comparison of the total levonorgestrel concentrations.


Hydration shell differentiates folded and disordered states of a Trp-cage miniprotein, allowing characterization of structural heterogeneity by wide-line NMR measurements.
Hydration properties of folded and unfolded/disordered miniproteins were monitored in frozen solutions by wide-line 1H-NMR. The amount of mobile water as function of T (-80 °C < T < 0 °C) was found characteristically different for folded (TC5b), semi-folded (pH < 3, TCb5(H+)) and disordered (TC5b_N1R) variants. Comparing results of wide-line 1H-NMR and molecular dynamics simulations we found that both the amount of mobile water surrounding proteins in ice, as well as their thaw profiles differs significantly as function of the compactness and conformational heterogeneity of their structure. We found that (i) at around -50 °C ~50 H2Os/protein melt (ii) if the protein is well-folded then this amount of mobile water remains quasi-constant up to -20 °C, (iii) if disordered then the quantity of the lubricating mobile water increases with T in a constant manner up to ~200 H2Os/protein by reaching -20 °C. Especially in the -55 °C ↔ -15 °C temperature range, wide-line 1H-NMR detects the heterogeneity of protein fold, providing the size of the hydration shell surrounding the accessible conformers at a given temperature. Results indicate that freezing of protein solutions proceeds by the gradual selection of the enthalpically most favored states that also minimize the number of bridging waters.


Draft Genome Sequences of Histamine-Producing Photobacterium kishitanii and Photobacterium angustum, Isolated from Albacore (Thunnus alalunga) and Yellowfin (Thunnus albacares) Tuna.
Histamine-producing bacteria are responsible for scombrotoxin (histamine) fish poisoning, a leading cause of fish poisoning in the United States. We report here the draft genome sequences of four histamine-producing (HP) Photobacterium kishitanii strains and nine HP Photobacterium angustum strains isolated from tuna.


Benefits of exercise in old age.
Although exercise capacity declines with age, the decline appears to be slight when measured in healthy, physically active subjects. There is growing evidence that exercise has a positive influence on increasing healthy function and decreasing the impact of diseases common in the elderly. While the dose-response relationship between physical activity and health benefits continues to be studied, there is some evidence that even low- and moderate-intensity exercise programs in older people result in tangible improvements in many physical and psychologic parameters.


Photodynamic enhancement of the activity of antibiotics used in urinary tract infections.
Photodynamic therapy (PDT) has been proven to kill different microbial cells. However, to our knowledge, none of the available reports describes the modulatory effect of this therapy on the antibacterial activity of antibiotics against Escherichia coli rods being the main causative agent of urinary tract infections (UTIs). Therefore, the aim of our study was to verify if the PDT can enhance the antibacterial activity of antibiotics recommended in the treatment of UTIs. An attempt to determine the optimal conditions of PDT to enhance the bactericidal activity of ciprofloxacin, amikacin, and colistin has been made. In order to find the optimal antimicrobial conditions, the efficacy of four protocols associated with the use of different energy doses (70 and 120 J/cm2) and chlorin e6 (Ce6) concentrations (50 and 100 μg/mL) has been verified. The antibacterial effect of combined PDT and antibiotics was assessed by the time-kill assay. The best results were achieved for Ce6 at a concentration of 100 μg/mL and the energy dose 120 J/cm2 for bacterial suspensions treated with ciprofloxacin. Taken together, our results showed that PDT using Ce6 improves the antibacterial activity of antibiotics effectively inhibiting bacterial growth and being promising in the elimination of bacterial UTIs in humans.


Synthesis and Characterization of Gold Nanorods and Their Application for Photothermal Cell Damage [Retraction].
[This retracts the article DOI: 10.2147/IJN.S11600.].


[Second tumors following chemotherapy of malignant tumors].
Alkylating cytostatic agents act in a carcinogenic manner on both human and animal. The results and findings of the animal experiments will be discussed shortly. Also, available data about the total dosages inducing carcinogenesis in humans, median induction times and the organotropy of the second tumors will be deliberated upon. Thus, a first attempt to toxicological quantification of the second tumors after alkylating treatment has been made.


Organization and plasticity of GABA neurons and receptors in monkey visual cortex.
The GABA neurons of monkey area 17 are a morphologically and chemically heterogeneous population of interneurons that are normally distributed most densely within the geniculocortical recipient zones of the visual cortex. In adult monkeys deprived of visual input from one eye, the levels of immunoreactivity for GABA and GAD within neurons of these geniculocortical zones is reduced. Similar changes are seen in the levels of proteins that make up the GABAA receptor sub-type. The effects of monocular deprivation on other substances suggest that specific types of GABA neurons, such as those in which the tachykinin neuropeptide family and parvalbumin coexist with GABA, are greatly influenced by changes in visual input. That some proteins remain normal within deprived-eye neurons and that other proteins are increased indicates the changes in the GABA cells of the cortex are not the result of a general reduction in protein synthesis. Comparisons of what is known about the morphological and synaptic features of GABA cells in area 17 and the characteristics of cells affected by monocular deprivation suggests that certain classes, such as the clutch cell, may be preferential targets of deprivation. Such a selective loss of certain GABA neurons would have broad implications for the possible physiological plasticity of cortical cells, for if ongoing studies determine that specific receptive field properties are affected by monocular deprivation in adults, the correlation of functional properties and classes of GABA cells would be possible.


Spontaneous inter-conversion of insulin fibril chirality.
Amyloid fibrils are associated with many neurodegenerative diseases and are considered to be the energetically most favorable form of proteins. Here we report that a small pH change initiates spontaneous transformation of insulin fibrils from one polymorph to another. As a result, fibril supramolecular chirality overturns both accompanying morphological and structural changes.


Virology and clinical sequelae of long-term antiviral therapy in a North American cohort of hepatitis B virus (HBV)/human immunodeficiency virus type 1 (HIV-1) co-infected patients.
There are limited recent data worldwide on clinical and virological outcomes in hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfected patients on dual active antiretroviral therapy (ART). We completed a retrospective review of 53 coinfected patients. HBV DNA in plasma was tested by PCR (sensitivity <20-<55 IU/ml or ∼100-300 copies/ml, Roche Diagnostics). Quantitative hepatitis B surface antigen (qHBsAg) was measured by an in-house assay (calibration range 0.24-62.5 IU/ml). HBV genotyping was done by line probe assay, and HBV variants determined by sequencing the HBV polymerase (P)/overlapping surface (S) gene. There were 7% (4/53) non-liver related deaths, ∼11% (6/53) had >F2 fibrosis, including 3 with cirrhosis. The median CD4+ T cell count was 415 cells/mm(3) (range 60-1310). 54% (28/51) were HBeAg-positive, and 81% (43/53) on ART had undetectable HBV DNA but only 5% (3/51) lost HBeAg. In 11/53 with HBV sequencing, 90% (10/11) were found to have HBV genotype A (HBV-A) and/or 27% (3/11) had a mixed A/G infection. Anti-HBV drug resistant mutations were detected in 54% (6/11) (i.e., any combination of rtV173L, rtL180M, M204V) and 45% (5/11) had an immune escape mutation (sP120S). In 12 with qHBsAg testing, the majority (9/12) had low-level qHBsAg ∼1-3 log(10) IU/ml. Liver disease occurs in ∼10% of coinfected patients on ART and many have low-level HBV DNA and qHBsAg. In those sequenced most were HBV-A or mixed A/G genotype, and several carry P and S mutants highlighting the complex molecular virology of HBV during HIV coinfection.


A changing climate and the dental profession.
Climate change is the defining crisis of our time and experts fear it is happening faster than first predicted. In November 2021, the UK hosted COP26 where world leaders met to coordinate actions and renew commitments to tackle the problem head on. Whether COP26 galvanised the international community enough to turn a corner remains to be seen; however, as dental professionals, we face significant considerations regarding our opportunities to effect positive change. The aim of this paper is to provide a short account of the impact of dentistry on the environment, as well as to highlight some challenges and the potential for change available to the dental profession to become more sustainability-conscious. In dentistry, the main sources of carbon emissions are travel, procurement and energy use. Prevention of oral and dental disease is the single most important factor in reducing the environmental impact of dentistry long-term. It is essential that clinicians, manufacturers and relevant stakeholders are united in dealing with the environmental crisis to bring about effective change. Clinicians and patients should be encouraged to consciously think about their impact on the environment and to consider what adjustments they can make to their clinical practice and oral health habits.


Clinical significance of metallothioneins in cell therapy and nanomedicine.
Mammalian metallothioneins (MTs) are low molecular weight (6-7 kDa) cysteine-rich proteins that are specifically induced by metal nanoparticles (NPs). MT induction in cell therapy may provide better protection by serving as antioxidant, anti-inflammatory, antiapoptotic agents, and by augmenting zinc-mediated transcriptional regulation of genes involved in cell proliferation and differentiation. Liposome-encapsulated MT-1 promoter has been used extensively to induce growth hormone or other genes in culture and gene-manipulated animals. MTs are induced as a defensive mechanism in chronic inflammatory conditions including neurodegenerative diseases, cardiovascular diseases, cancer, and infections, hence can serve as early and sensitive biomarkers of environmental safety and effectiveness of newly developed NPs for clinical applications. Microarray analysis has indicated that MTs are significantly induced in drug resistant cancers and during radiation treatment. Nutritional stress and environmental toxins (eg, kainic acid and domoic acid) induce MTs and aggregation of multilamellar electron-dense membrane stacks (Charnoly body) due to mitochondrial degeneration. MTs enhance mitochondrial bioenergetics of reduced nicotinamide adenine dinucleotide-ubiquinone oxidoreductase (complex-1), a rate-limiting enzyme complex involved in the oxidative phosphorylation. Monoamine oxidase-B inhibitors (eg, selegiline) inhibit α-synuclein nitration, implicated in Lewy body formation, and inhibit 1-methyl 4-phenylpyridinium and 3-morpholinosydnonimine-induced apoptosis in cultured human dopaminergic neurons and mesencephalic fetal stem cells. MTs as free radical scavengers inhibit Charnoly body formation and neurodegenerative α-synucleinopathies, hence Charnoly body formation and α-synuclein index may be used as early and sensitive biomarkers to assess NP effectiveness and toxicity to discover better drug delivery and surgical interventions. Furthermore, pharmacological interventions augmenting MTs may facilitate the theranostic potential of NP-labeled cells and other therapeutic agents. These unique characteristics of MTs might be helpful in the synthesis, characterization, and functionalization of emerging NPs for theranostic applications. This report highlights the clinical significance of MTs and their versatility as early, sensitive biomarkers in cell-based therapy and nanomedicine.


Alternative induction of alpha/beta interferons and gamma interferon by listeria monocytogenes in mouse spleen cell cultures.
Production of interferon (IFN) by Listeria monocytogenes (LM) in nonimmunized mouse spleen cell cultures was studied. IFN-gamma defined by virtue of its acid stability and antigenicity was produced in spleen cell cultures obtained from ddY mice, C57BL/6 mice, and BALB/c mice in response to heat-killed (HK) LM within 24 hr. On the other hand, production of IFN-alpha/beta was demonstrated in spleen cell cultures obtained from one of four nude mice (BALB/c, nu/nu). Therefore, it is important to know the reason why the spleen cells of mice other than nude mice did produce only IFN-gamma, but did not produce IFN-alpha/beta in response to HK-LM. Spleen cells obtained from ddY mice were fractionated, and the cellular source for IFN production of either IFN-alpha/beta or IFN-gamma induced by HK-LM was investigated. IFN-gamma was produced only by a mixture of T lymphocytes (nylon wool-nonadherent, Thy-1-positive cells) and macrophages by HK-LM. Neither T lymphocytes nor macrophages alone produced IFN by HK-LM. Macrophage-depleted spleen cells produced neither IFN-gamma nor IFN-alpha/beta, but these cells acquired the ability to produce IFN-alpha/beta, not IFN-gamma, only when they had been treated with IFN-alpha/beta. A possible mechanism of both IFN-gamma and IFN-alpha/beta induction by Listeria in mouse spleen cell cultures is discussed.


[Role of innate receptors in chronic inflammation and autoimmunity].
Elucidating the basis of chronic disease courses and the development of appropriate treatment methods for inflammatory diseases still represent a big challenge for medical science, as the mechanisms driving aberrant immune reactions are mostly still unknown. Of particular interest is the identification of checkpoints that regulate the function and differentiation of proinflammatory cells during the pathogenesis, along with methods for modulation of specific checkpoints as a treatment approach. Innate receptors, such as members of the natural killer group 2 family (NKG2X), natural cytotoxicity receptors (NCR) or Toll-like receptors (TLRs), play an important role in modulating the immune response. NKG2 member D (NKG2D) is a potent activating receptor of the immune system, known as a sentinel for cellular danger signals presented by cells exposed to endoplasmic reticulum (ER) stress, cell death or an inflammatory cytokine milieu. NKG2A/C bind the non-classical HLA class I molecule, sense changes in ligand expression associated with malignant transformation and cellular stress and their main function is to send inhibitory or activating signals to NK cells and subsets of T cells. In this review, we present our latest knowledge on the understanding of the role of innate receptors in the context of chronic inflammation and autoimmunity with special emphasis on danger sensor receptors NKG2D and NKG2A/C.


Electro-optics of colloid-polyelectrolyte complexes: counterion release from adsorbed macromolecules.
Complexation between sodium carboxymethylcellulose (NaCMC) and ellipsoidal particles of oppositely charged beta-FeOOH is studied using electric light scattering and electrophoresis. We focus on the complex behavior for overcharging of the particle surface. In this case, the fraction of condensed counterions on NaCMC is found to remain unchanged during polymer adsorption onto a weakly charged particle surface. Using the theory of Sens and Joanny, we evaluate the fraction of condensed counterions and compare it with results for nonadsorbed NaCMC. The polarization of condensed counterions along the chain of the adsorbed macromolecule is proved to create the electro-optical effect in suspensions stabilized by NaCMC adsorption.


Arginine and glutamine supplementation on transthyretin levels in severely burned patients: A systematic review.
The aim of this study was to investigate the influence of supplementation with the immunomodulators arginine and glutamine on transthyretin levels in burn patients. This systematic review followed the protocol proposed and registered in PROSPERO (CRD42021239526) and was carried out following the PRISMA checklist for systematic reviews. Forty-four studies were evaluated. Of the 44, we included 6 for complete analysis. In five of the six clinical trials, glutamine was the most used immunomodulator (0.5 g·kg·d-1 or 12-14 g/d), followed by arginine in three of the clinical trials (10-14 g/d in adults or 2% of total energy value in children). The findings of the studies were that the patients who received either of these supplements presented the following results: increased transthyretin, lymphoproliferative response, and serum glutamine values, as well as shorter stay in the intensive care unit, a significant reduction in C-reactive protein values, and a tendency toward a faster healing of the burns compared with the control groups. In view of the content in the present review, it is possible to affirm that the supplementation of immunomodulators in burn patients is an effective strategy for their treatment, and that the adequate nutritional offer may be a predictor of a favorable outcome. However, regarding the increase in transthyretin values, this finding needs to be considered with reservations as the values can be altered by the inflammatory activity, and not necessarily related to the use of a supplement.


Balancing mucosal immunity: caught between CYLD and Charybdis.
The molecular mechanism of acute lung injury caused by Streptococcus pneumoniae is unclear. In this issue of Immunity, Lim et al. (2007) demonstrate that CYLD, a deubiquinating enzyme, represses the expression of plasminogen activator inhibitor-1, which is critical in preventing tissue damage.


Bacteremia and fungemia complicating neoplastic disease. A study of 364 cases.
During a 14 month period there were 364 episodes of bacteremia and fungemia at Memorial Sloan-Kettering Cancer Center. The first nine months of the study were retrospective, and the next five prospective. In patients with leukemia or lymphoma (group 1), Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus were the most frequently isolated organisms. The mortality in this group was 40.5 per cent. In the patients with solid tumor (group 2), Esch. coli, Staph. aureus, Bacteroides sp. and Candida sp. were most frequent. Mortality was 27.8 per cent. The source of infection in both groups was often indeterminate. High mortality was associated with pulmonary and intraabdominal infection and with Ps. aeruginosa, K. pneumoniae or polymicrobic sepsis. Factors of prognostic significance were the causative microorganism, source of infection and shock. Although mortality was higher in patients with leukopenia than in those with normal leukocyte counts, the differences were not significant. The mortality in this series was low considering the severity of the underlying diseases and the immunosuppressed state of many of the patients. In a prospective, randomly controlled study, mortality was further diminished by infectious disease consultation at the time the positive blood culture was reported. Severe fungal superinfection, predominantly aspergillosis and candidiasis, was found in 52 per cent of the autopsy patients with leukemia or lymphoma (group 1), but in only 8 per cent of those with solid tumors (group 2).


Yoga as part of a package of care versus standard care for schizophrenia.
Yoga is an ancient spiritual practice that originated in India and is currently accepted in the Western world as a form of relaxation and exercise. It has been of interest for people with schizophrenia to determine the efficacy of yoga delivered as a package of care versus standard care. To examine the effects of yoga as a package of care versus standard care. We searched the Cochrane Schizophrenia Group Trials Register (latest 30 March 2017) which is based on regular searches of MEDLINE, PubMed, Embase, CINAHL, BIOSS, AMED, PsychINFO, and registries of clinical trials. We searched the references of all included studies. There are no language, date, document type, or publication status limitations for inclusion of records in the register. All randomised controlled trials (RCTs) including people with schizophrenia comparing yoga as a package of care with standard-care control. The review authors independently selected studies, quality rated these, and extracted data. For binary outcomes, we calculated risk difference (RD) and its 95% confidence interval (CI), on an intention-to-treat (ITT) basis. For continuous data, we estimated the mean difference (MD) between groups and its CI. We employed mixed-effect and fixed-effect models for analysis. We examined heterogeneity (I2 technique), assessed risk of bias for included studies, and created a 'Summary of findings' table using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Three studies are included in this review. All outcomes were short term (less than eight weeks). Useable data were reported for two outcomes only; leaving the study early and quality of life. None of the participants left the studies early and there was some evidence in favour of the yoga package for quality of life endpoint scores (1 RCT, n=80, MD 22.93 CI 19.74 to 26.12, low-quality evidence). Leaving the study early data were equivocal between the treatment groups (3 RCTs, n=193, RD 0.06 CI -0.01 to 0.13, medium-quality evidence, high heterogeneity). Overall, this review has an inordinate number of missing key outcomes, which included mental and global state, social functioning, physical health, adverse effects and costs of care. A small number of small studies were included in this review and these lacked many key outcomes. The sparse data means we cannot state with any degree of certainty if yoga delivered as a package of care is beneficial in comparison to standard care.


In Vitro Effect of Different Airflow Rates on the Aerosol Properties of Nebulized Glycopyrrolate in the eFlow® Closed System and Tiotropium Delivered in the HandiHaler®.
Personalized therapy for patients with COPD requires appropriate choice of drug and delivery device. Inhalers and nebulizers vary in their drug delivery characteristics, particularly the need for passive or active patient inhalation for appropriate drug dispersal and delivery. In this in vitro analysis, we assessed the aerosol performance and drug delivery of two long-acting muscarinic antagonists, glycopyrrolate (GLY; 25 µg solution; 1 ml) and tiotropium (TIO; 18 µg powder) through their respective delivery systems: the eFlow® Closed System (CS) vibrating membrane nebulizer and the HandiHaler® dry-powder inhaler (DPI). The aerosol performances of the eFlow® CS nebulizer and the HandiHaler® were determined using the Next Generation cascade Impactor. The delivered dose of GLY and TIO was determined using different breathing patterns, which varied in tidal volume and peak inspiratory flow rate, respectively, to simulate breathing conditions ranging from normal to severe obstruction. Aerodynamic particle analysis showed generally similar mass median aerodynamic diameter (MMAD, range, 3.6-4.6 µm) and fine particle fraction (FPF, range, 48.2%-63.7%) with GLY delivered using the eFlow® CS nebulizer under all breathing patterns tested. TIO, delivered via the HandiHaler®, showed variations in MMAD (range, 3.8-5.8 µm) and FPF (range, 16.1%-32.4%) under different inspiratory flow rates. The majority of GLY was deposited in stages 2-5 of the impactor, which corresponds with particle sizes in the respirable range (< 5 µm), whereas a large proportion of TIO was deposited in the throat/mouthpiece pre-separator, irrespective of test conditions. The median residual dose of GLY with eFlow® CS was notably lower compared to that of TIO with HandiHaler® (2.4%-4.4% vs. 40%-67%, respectively). These simulation results highlight the different deposition patterns generated by a DPI device and a vibrating membrane nebulizer, which may help inform device selection and treatment decision in COPD management.


Complement and protease inhibitors in the mucocutaneous lymph node syndrome.
Total hemolytic activity of serum (CH50), complement components C3 and C4, alpha 1antitrypsin (alpha 1AT), alpha 1antichymotrypsin (alpha 1X), antithrombin III (AT III), alpha 2 macroglobulin (alpha 2M), and inter-alpha-inhibitor (I-alpha-I) were measured in 23 Japanese and 19 European children with the Mucocutaneous Lymph node Syndrome (MCLS) during the acute phase of disease. Second sera, obtained after day 20 were available from 18 Japanese and 10 European children. In 28 out of 31 children with mild disease, as assessed by the coronary risk score of Asai and Kusakawa, complement was normal or elevated during the acute phase. In 10 out of 11 children with high risk scores, CH50 was below the normal range. One child in this group had ECG changes during the acute phase, one patient died and two others developed coronary aneurysms. C1I was elevated in all 42 cases, alpha 1AT in 40, and alpha 1X in 38 patients. alpha 1AT was depressed in two children, one of whom developed an aneurysm. One of the four children with depression of alpha 1X died of myocardial infarction. Decreased concentrations of AT III, alpha 2M and I-alpha-I were frequent and tended to mark the more severe courses of the disease. A third group of 20 children was evaluated 5 weeks to 6 months after the acute illness. Mean concentrations of all five protease inhibitors were completely normalized in this group. The results of this study indicate that consumption of complement and of protease inhibitors occurs in many cases of MCLS during the acute phase. Determination of CH50 appears to be useful to identify high risk patients early in the course of their illness. Transient deficiency of substances for control of inflammation may in part be responsible for the severe vascular lesions seen in some patients.


Klebsiella serotype-13 capsular polysaccharide: primary structure and depolymerization by a bacteriophage-borne glycanase.
Periodate oxidation and Smith degradation, methylation analysis including uronic acid degradation, partial hydrolysis with acid, bacteriophage degradation, and p.m.r. spectroscopy have been used to elucidate the primary structure of the Klebsiella serotype-13 capsular polysaccharide. The polymer consists of pentasaccharide repeating-units comprising a 4)-beta-D-Manp-(1 leads to 4)-alpha-D-Glcp-(1 leads to 3)-beta-D-Glcp-(1 leads to chain with a 3,4-O-(1-carboxyethylidene)-beta-D-Galp-(1 leads to 4)-alpha-D-GlcAp-(1 leads to branch at position 3 of the mannose. It is shown that there is a glycanase activity associated with particles of Klebsiella bacteriophage No. 13, which catalyses hydrolysis of chain beta-D-Glcp-(1 leads to 4)-beta-D-Manp linkages in the type-13 polysaccharide. The chemical basis of some serological cross-reactions of the Klebsiella K13 antigen is discussed.


[Monogenic heart disease].
The pathogenesis of most cardiovascular disorders is multifactorial and incompletely understood. Besides genetic influences that often arise from multiple genetic loci, the specific nutritional and environmental influences do contribute to the dysfunctional development. Nevertheless, a rather small number of cardiovascular diseases exhibits Mendelian traits, since they are caused by a single gene defect. Examples are familial cardiomyopathies, primary arrhythmias and connective tissues disorders of vessels. More detailed investigations reveal that even these entities are usually not purely monogenic, as they do not appear with the same intensity in all mutation carriers. Hence, there must be further modifying factors that influence the penetrance of the disease. Despite this limitation monogenic diseases allow the identification of the underlying genetic defects and thereby a deeper insight into the pathophysiology. Predictive genetic diagnostics, on the other hand, permit a better adaptation of medical care to the individual risk of offspring that are not yet affected.


Pyrazolo[1,5-a]pyrimidine CRF-1 receptor antagonists.
A series of 3-phenylpyrazolo[1,5-a]pyrimidines was prepared and found to have affinity for the human CRF-1 receptor. The 3-dimensional structure of one of the most potent analogs in this series, 10d, was determined by X-ray crystallography and suggests the spatial requirements for potent CRF-1 receptor binding affinity in this series.


The distribution of cellular retinoic acid-binding protein I during odontogenesis in the rat incisor.
Retinoids are important molecules in various aspects of embryological development. Here the distribution of cellular retinoic acid-binding protein I (CRABPI) was studied in the continuously growing incisor of adult rats using an affinity-purified rabbit polyclonal antibody. CRABPI was present throughout the presecretory and secretory ameloblast layer. The protein disappeared from that layer during its maturation phase. The adjacent dental mesenchyme of the developing pulp stained positively for CRABPI, especially in the layer immediately beneath the fully differentiated odontoblasts. Little CRABPI was present in the odontoblast layer itself. The distribution of CRABPI, both in the undifferentiated basal region of the incisor tooth and associated with the cells during hard-tissue formation, suggests a role for this molecule during differentiation and hard-tissue genesis.


Correction: Association Between State Indoor Tanning Legislation and Google Search Trends Data in the United States From 2006 to 2019: Time-Series Analysis.
[This corrects the article DOI: 10.2196/26707.].


[АComparative analysis of the magnitude of the distance and lens-induced objective accommodative response in patients with different refraction].
To study the magnitude of objective accommodative response (OAR) with account to the method of image defocusing. The latter can be realized by bringing the object nearer to the eye or by adding a minus lens in front of the viewer. We examined 63 patients (126 eyes) with different refraction aged from 7 to 31 years. All patients underwent a series of OAR measurements on WR-5100K Grand Seiko Binocular Open-Field Autorefkeratometer under different conditions, including negative spherical lenses of -3.0 D and -5.0 D, test optotypes corresponding to visual acuity of 0.2 and 0.7 and presented at a distance of 5 m, and a set of variably sized optotypes presented at a distance of 33 cm and 20 cm. A disparity was found between the magnitude of accommodative responses evoked through different means: placing a negative lens in front of the viewer while he/she looks into the distance or bringing the object closer to the eye. In almost all cases lens-induced responses were less pronounced than distance-induced. In all myopic children, accommodative lag was longer at near than at distance. Generally, in all groups, OAR to distant objects as well as responses to a 3.0 D accommodative task at near did not depend on the size of the object. There was an insignificant and statistically unreliable difference for objects placed 20 cm away (5.0 D accommodative task): OAR to a smaller font was stronger than that to a larger one. In children and adults with emmetropia, hyperopic children, and myopic adults, longer accommodative lags were characteristic of lens-induced responses. In children with myopia, longer lags were observed at near. Moreover, at near, OAR to a smaller font was stronger than that to a larger one.


Velar Movements during speech in two Wernicke aphasic patients.
The articulatory gestures of the velum in two Wernicke aphasic patients were examined to compare their performances with those of an apraxic patient by means of the fiberoptic technique. In contrast to the marked variability in the apraxic performance in terms of velum height and segmental duration, the two fluent aphasic subjects showed a relatively high degree of consistency in velar movements throughout several repetitions of nonsense syllables and meaningful words. In addition, both patients exhibited a normal pattern of anticipatory coarticulation. Analyses of the velar movement patterns during the speech-sound error processes of both patients suggested that these errors were not due to an impairment at the level of articulatory programming but to an error in the selection of a target phoneme.


Comprehensive Evaluation of Vocal Outcomes and Quality of Life after Total Laryngectomy and Voice Restoration with J-Flap and Tracheoesophageal Puncture.
Tracheoesophageal puncture with a voice prosthesis is the gold standard for speech rehabilitation in patients that receive a laryngopharyngectomy. However, a novel surgical technique, using a tubularized anterolateral tight flap, named "J-flap," has been demonstrated to produce adequate voice restoration. We aimed to compare the outcomes and the quality of life of patients who underwent voice rehabilitation with both techniques. We enrolled patients that underwent laryngopharyngectomy and voice restoration surgery. The control group received a tracheoesophageal puncture with a voice prosthesis, while the study group received J-flap reconstruction. A total of 20 patients received voice prosthesis rehabilitation, while 18 received J-flap reconstruction. Speech and vocal outcomes and quality of life metrics were collected. The objective phonatory performances and the acoustic voice analysis did not outline a significant difference. Speech pathologists judged the consonant pronunciation in the J-flap group as less accurate (p < 0.001). The voice handicap index revealed a moderate impairment for the J-flap group (p < 0.001). Quality of life scores were higher for the voice prosthesis group. Voice prostheses and J-flaps share similar objective phonatory outcomes. Quality of life was more impaired in the J-flap group. In our view, these two techniques possess complementary characteristics in clinical practice, taking into account health care system regulations and patients' social background.


Congenital hydrops fetalis describes an abnormal accumulation of fluid in two or more compartments in a fetus. The disease is categorized based on the aetiology: immune- and non-immune hydrops fetalis. Today, the non-immune form is the most common. Once born, the child is initially handled symptomatically and will often need intensive care and treatment. Even though approximately one in five cases is still idiopathic, genetic diagnostic tools have become increasingly important in the diagnostic process. The prognosis depends on the aetiology and the gestational age when diagnosed and at birth, as argued in this review.


Sutureless amniotic membrane transplantation for partial limbal stem cell deficiency.
To evaluate the results of sutureless amniotic membrane (AM) transplantation using fibrin glue for reconstructing corneal surfaces with partial limbal stem cell deficiency (LSCD). Retrospective noncomparative interventional case series. Eleven eyes of nine patients that had LSCD with 120 degrees to almost 360 degrees of limbal involvement underwent superficial keratectomy to remove the conjunctivalized pannus followed by AM transplantation using fibrin glue. Additional sutureless AM patch (ProKera; Bio-Tissue, Inc, Miami, Florida, USA) was used in seven patients, and mitomycin C was applied on the cornea in four eyes and during fornix reconstruction in seven eyes. The surgery was repeated in three eyes for residual pannus. During a mean follow-up of 14.2 +/- 7.7 months (range, six to 26 months), all eyes maintained a smooth and stable corneal epithelial surface without recurrent erosion or persistent epithelial defect, and showed less stromal cloudiness and vascularization. Best-corrected visual acuity improved in nine eyes (81.8%). Corneal epithelialization proceeded by epithelial growth over AM (n = 4), accompanied by dissolution of AM (n = 4) or a combination of both (n = 3). No complication was noted regarding initial or repeated uses of fibrin glue. AM transplantation using fibrin glue appears to be a safe and effective method of restoring a stable corneal epithelium for cases with partial LSCD. This approach avoids the need of transplanting limbal epithelial stem cells.


Author Correction: Development and long-term evaluation of a new 68Ge/68Ga generator based on nano-SnO2 for PET imaging.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


The scope for pneumococcal vaccines that do not prevent transmission.
The pneumococcal vaccine pipeline holds candidates developed with the aim to prevent the majority if not all pneumococcal disease. Herd protection is a critical component of the overall impact of current pneumococcal conjugate vaccines (PCVs) and is a prerequisite for disease elimination through an infant vaccination programme. We assessed the scope of a hypothetical pneumococcal vaccine candidate (HPVC) with high clinical efficacy against all pneumococci but that fails to induce such indirect protection. We found that, despite a lack of impact on unvaccinated individuals, HPVC use in infancy may offer similar or superior impact among young children if compared to current PCVs. Hence, it could provide a more affordable alternative to PCVs in particular in settings where most pneumococcal disease is concentrated in children.


The ubiquitin-specific protease 8 antagonizes melatonin-induced endocytic degradation of MT1 receptor to promote lung adenocarcinoma growth.
The human genome encodes two melatonin receptors (MT1 and MT2) that relay melatonin signals to cellular interior. Accumulating evidence has linked melatonin to multiple health benefits, among which its anticancer effects have become well-established. However, the implications of its receptors in lung adenocarcinoma have so far remained incompletely understood. This study aims to investigate the response of the MT1 receptor to melatonin treatment and its dynamic regulation by ubiquitin-specific protease 8 (USP8) in lung adenocarcinoma. The mRNA levels of MT1 and MT2 receptors were analyzed with sequencing data. The expression and localization of the MT1 receptor with melatonin treatment were investigated by immunoblotting, immunofluorescence and confocal microscopy assays. Endocytic deubiquitylases were screened to identify MT1 association. The effects of USP8 were assessed with shRNA-mediated knockdown and small molecule inhibitor. The combined efficacy of melatonin and USP8 suppression was also evaluated using xenograft animal models. Bioinformatic analysis revealed increased expression of the MT1 receptor in lung adenocarcinoma tissues. Melatonin treatment leads to the downregulation of the MT1 receptor in lung adenocarcinoma cells, which is attributed to receptor endocytosis and lysosomal degradation via the canonical endo-lysosomal route. USP8 negatively regulates the endocytic degradation of the MT1 receptor incurred by melatonin exposure and thus protects lung adenocarcinoma cell growth. USP8 suppression by knockdown or pharmacological inhibition effectively deters cancer cell proliferation and sensitizes lung adenocarcinoma cells to melatonin in vitro. Furthermore, USP8 silencing significantly potentiates the anticancer effects of melatonin in xenograft tumor models. The MT1 receptor responds to melatonin treatment and is endocytosed for lysosomal degradation that is counteracted by USP8. The inhibition of USP8 demonstrates tumor-suppressive effects and thus can be exploited as potential therapeutic strategy either as monotherapy or combined therapy with melatonin.


Light microscopic detection of sugar residues in glycoconjugates of salivary glands and the pancreas with lectin-horseradish peroxidase conjugates. II. Rat.
Salivary glands and pancreases from male rats were stained with a battery of ten different lectin-horseradish peroxidase conjugates. Qualitative and quantitative differences were observed in the content of terminal sugar residues in stored secretory glycoproteins in parenchymal cells of glands having a similar histological structure. Heterogeneity in the content of secretory glycoconjugates was also found between cells in the same exocrine glands, which were previously thought to be identical on the basis of classical morphological and histochemical staining studies. Similar differences were observed in the structure of glycoconjugates associated with the apical surface of epithelial cells lining glandular excretory ducts. Intercalated ducts presented a gland specific staining pattern different from that of the glandular secretory cell population, whereas striated duct and interlobular duct epithelial cells stained similarly in all major rat exocrine glands. A comparison of lectin binding patterns in identical histological sites in the mouse, reported in a companion paper, is provided, and the similarities and differences between these two rodent species are discussed. In addition to providing valuable information concerning the localization and structure of tissue complex carbohydrates, a comparison of staining in the same tissue sites with labelled lectins reported biochemically to have similar binding specificity has revealed interesting differences in the binding specificity of these macromolecules.