Cerebral glucose metabolism abnormalities in patients with major depressive symptoms in pre-dialytic chronic kidney disease: statistical parametric mapping analysis of F-18-FDG PET, a preliminary study.
The aim of the present study was to investigate the relationship between depressive symptoms and cerebral glucose metabolism in pre-dialytic chronic kidney disease (PDCKD) patients. Twenty-one patients with stage 5 CKD and 21 healthy volunteers underwent depressive mood assessment and statistical parametric mapping (SPM) using F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET). Several voxel clusters of significantly decreased cerebral glucose metabolism were found in PDCKD patients. The largest cluster was left prefrontal cortex (Brodmann area [BA] 9). The second largest cluster was also left prefrontal cortex (BA 9). The third largest clusters were right prefrontal cortex (BA 10) and right basolateral prefrontal cortex (BA 46). Other brain areas also showed decreased cerebral glucose metabolism including left anterior cingulate gyrus (BA 32), left premotor cortex (BA 6), left transverse temporal gyrus (BA 41), left superior temporal gyrus (BA 42), right basolateral prefrontal cortex (BA 44), right inferior parietal lobule (BA 39), left middle temporal gyrus (BA 19), and left angular gyrus (BA 39). Hypermetabolized brain areas, however, were not found in PDCKD patients compared to normal controls. For the right orbitofrontal cortex there was a negative correlation of cerebral glucose metabolism with Hamilton Depression Rating Scale (HDRS) in PDCKD patients (BA 11). PDCKD patients with depressive symptoms had decreased cerebral glucose metabolism in several brain areas. For the right orbitofrontal cortex there was a negative correlation with HDRS in PDCKD patients. The present findings provide functional neuroimaging support for abnormal cerebral glucose metabolism in PDCKD patients with depressive symptoms.


Glued intraocular lens in eyes with deficient capsules: retrospective analysis of long-term effects.
To assess the long-term (6-12 years) results and complications of glued transscleral-fixated intraocular lens (IOL). Dr. Agarwal's Eye Center, Chennai, India. Retrospective case series. Eyes with glued IOL of more than 5-year follow-up were evaluated. Visual acuity (logarithm of the minimum angle of resolution [logMAR]), IOL tilt, corneal topography, corneal endothelial cell density, intraocular pressure, central corneal thickness, central foveal thickness, and ocular residual astigmatism (ORA) were evaluated. Overall, 91 eyes (63 patients) with mean postoperative 8.2 ± 2.3 years were analyzed. The duration was 10 to 12 years in 31 eyes (34%), 9 years in 14 eyes (15.3%), and 6 to 9 years in 46 eyes (50.5%). No subscleral haptic was visible in 50% eyes. Mild, moderate, and severe grade of haptic visibility was noted in 33.5%, 9.4%, and 7%, respectively. The corrected distance visual acuity (CDVA) was 0.50 ± 0.50 logMAR. Clinically, no tilt was seen in 87 eyes (95.6%), whereas detectable tilt was seen in 4 eyes (4.3%). The optical coherence tomography microtilt was 0.8 ± 1.7 and 0.4 ± 1.2 degrees in 90- and 180-degree axes, respectively. The mean iris vault was 0.45 mm, and the mean ORA was 1.10 ± 1.00 diopter. Complications were glaucoma (7.6%), IOL luxation (4.4%), retinal detachment (3.2%), macular edema (4.3%), corneal decompensation (3.2%), uveitis (2.1%), and uveitis-glaucoma-hyphema syndrome (1%). Haptic reposition (3.2%), retinal detachment surgery (3.2%) keratoplasty (1%), pupilloplasty (2.1%), and IOL explantation (1%) were the second surgeries performed. Glued IOL has shown good anatomical and functional stability with minimal incidence of vision-threatening complications on long-term.


The protective effect of different airway humidification liquids to lung after tracheotomy in traumatic brain injury: The role of pulmonary surfactant protein-A (SP-A).
The purpose of this study was to establish a rat model of a brain injury with tracheotomy and compared the wetting effects of different airway humidification liquids, afterward, the best airway humidification liquid was selected for the clinical trial, thus providing a theoretical basis for selecting a proper airway humidification liquid in a clinical setting. Rats were divided into a sham group, group A (0.9% NaCl), group B (0.45% NaCl), group C (0.9% NaCl+ambroxol) and group D (0.9% NaCl+Pulmicort). An established rat model of traumatic brain injury with tracheotomy was used. Brain tissue samples were taken to determine water content, while lung tissue samples were taken to determine wet/dry weight ratio (W/D), histological changes and expression levels of SP-A mRNA and SP-A protein. 30 patients with brain injury and tracheotomy were selected and divided into two groups based on the airway humidification liquid instilled in the trachea tube, 0.45% NaCl and 0.9% NaCl+ambroxol. Blood was then extracted from the patients to measure the levels of SP-A, interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α). The difference between group C and other groups in lung W/D and expression levels of SP-A mRNA and SP-A protein was significant (P<0.05). In comparison, the histological changes showed that the lung tissue damage was smallest in group C compared to the three other groups. Aspect of patients, 0.45% NaCl group and 0.9% NaCl+ambroxol group were significantly different in the levels of SP-A, IL-6, IL-8 and TNF-α (P<0.01). In the present study, 0.9% NaCl+ambroxol promote the synthesis and secretion of pulmonary surfactant, and has anti-inflammatory and antioxidant effects, which inhibit the release of inflammatory factors and cytokines, making it an ideal airway humidification liquid.


Biliary complications in right lobe living donor liver transplantation.
Living donor liver transplantation is an alternative to deceased donor liver transplantation in the face of insufficient deceased donor liver grafts. Unfortunately, the incidence of biliary complication after living donor liver transplantation is significantly higher than that after deceased donor liver transplantation using grafts from non-cardiac-death donations. The two most common biliary complications after living donor liver transplantation are bile leakage and biliary anastomotic stricture. Early treatment with endoscopic and interventional radiological approaches can achieve satisfactory outcomes. If treatment with these approaches fails, the salvage measure for prompt rectification will be surgical revision, which is now seldom performed. This paper also discusses risk factors in donor biliary anatomy that can affect recipients.


Black box analysis of the skin senses as a multiple communication channel.
The skin senses have been investigated as a multichannel parallel information system. In psychophysical experiments using two cold two warmth and two vibration stimuli the capability of these senses have been determined for transmitting independent parallel information. A black box model is used to describe interactions within the system between pairs of signals causing two different response components in a multiple response after multimodal activation. The theory distinguishes two kinds of interaction, those between internal noise sources and between internal signal sources. It appears that the skin senses show only a very small interaction of their respective noise sources whereas their signal sources interact extensively. The repercussions for the skin as a parallel information transmitter is discussed shortly in the context of a development of an optimum "skin vision" system, which should project an environment onto the skin, employing both the sense of touch and the sense of temperature.


Continuous monitoring of oxygen saturation in prehospital patients with severe illness: the problem of unrecognized hypoxemia.
The continuous measurement of arterial oxygen saturation using pulse oximetry (SpO2) has become popular for critically ill hospitalized patients. Its use in the ambulance transfer of similarly ill patients has been infrequently documented. This study examines the use of prehospital pulse oximetry, with special reference to the ability of ambulance attendants to recognize hypoxemia. Using a prospective single-blind case series method, a convenience sample of adult patients transferred by ambulance designated Code 3 (serious but not life threatening) or Code 4 (serious and life threatening) to a regional base hospital were examined for the presence of hypoxemia. An Ohmeda finger pulse oximeter probe was attached to all patients. Prior to the study, oxygen treatment was reviewed and ambulance personnel were instructed on the use of the instrument. The continuous oxygen saturation record was not revealed to the attendant(s) during the cell. Administration of oxygen was monitored, and a study form was completed by the attendant at the completion of the call. Overall, 50 patients were included in the study. The most common complaints were chest pain 21 (37%) and shortness of breath 15 (27%). The average age was 64 years, with a range of 32-82. Hypoxemia, defined as SpO2 of less than 90% for more than 1 minute, was detected in 14 patients. Attendants recognized hypoxemia on clinical grounds in only 4 patients (sensitivity = 28%). Forty-one (82%) patients received various amounts of supplemental oxygen; many patients remained hypoxemic despite therapy.(ABSTRACT TRUNCATED AT 250 WORDS)


Deleterious impact of hyperglycemia on cystic fibrosis airway ion transport and epithelial repair.
Cystic fibrosis (CF)-related diabetes (CFRD) is associated with faster pulmonary function decline. Thus, we evaluated the impact of hyperglycemia on airway epithelial repair and transepithelial ion transport, which are critical in maintaining lung integrity and function. Non-CF and CF airway epithelial cells were exposed to low (LG) or high (HG) glucose before ion current and wound repair rate measurements. CFTR and K+ currents decreased after HG treatments. HG also reduced the wound healing rates of non-CF and CF cell monolayers. Although CFTR correction with VRT-325 accelerated the healing rates of CF cells monolayers under LG conditions, this improvement was significantly abrogated under HG conditions. Our data highlights a deleterious impact of hyperglycemia on ion transport and epithelial repair functions, which could contribute to the deterioration in lung function in CFRD patients. HG may also interfere with the beneficial effects of CFTR rescue on airway epithelial repair.


Spatio-temporal patterns of road traffic noise pollution in Karachi, Pakistan.
We studied the spatial and temporal patterns of noise exposure due to road traffic in Karachi City, Pakistan, and found that levels of noise were generally higher during mornings and evenings because of the commuting pattern of Karachi residents. This study found the average value of noise levels to be over 66 dB, which could cause serious annoyance according to the World Health Organization (WHO) outdoor noise guidelines. Maximum peak noise was over 101 dB, which is close to 110 dB, the level that can cause possible hearing impairment according to the WHO guidelines. We found that noise pollution is not an environmental problem reserved for developed countries, but occurs in developing countries as well. For this reason, steps might be required to reduce noise levels caused by road traffic.


Rapid detection of cytomegalovirus structures in cerebrospinal fluid and brain biopsies by polymerase chain reaction.
The joint application of stereotactic brain biopsy and DNA amplification methods, like the polymerase chain reaction (PCR) are diagnostic purposes that allows in approximately 24 h to clarify the viral etiology of central nervous system infections. We demonstrate PCR results from the brain biopsy of an HIV-1 patient with two cerebral lesions. Beside the neuropathological diagnosis of a B-cell non-Hodgkin lymphoma the experimental results are indicative of active transcription of cytomegalovirus (CMV) in cerebral tissue. The markedly higher amount of CMV-specific RNA found in the biopsy specimens and CSF suggest the presence of an active infection with viral replication. CT-guided stereotactic brain biopsies followed by PCR fulfill the demands of a clinician, namely to get the results as fast as possible to initiate adequate treatment.


[Technology transfer between academic laboratories and industrial laboratories: licensing].
The time when academic and industrial research were operating in two separate worlds is now over. Technology transfer from one to the other is now frequent and organized. It starts by filing a patent. Of course, provided the amounts at stake for developing a product, especially in the healthcare field, a non patent-protected invention has virtually no chance of eventually reaching the community. But this is only the first step of a long process which starts by licensing deals of which we will examine the main common clauses.


In Situ Surface-Initiated ATRP Mediated by Gallium-Based Liquid Metal Nanodroplets.
Surface-initiated atom transfer radical polymerization (SI-ATRP) is one of the most popular methods for surface modifications with functional polymer films, which has attracted significant attention in recent years. Herein, a facile method of gallium-based liquid metal (GLM) nanodroplets mediated SI-ATRP to prepare polymer brushes on GLM surfaces is reported. The ATRP initiator modified GLM (GLM-Br) nanodroplets act as a substrate for the in situ SI-ATRP and participate as a reducing agent to reduce Cu(II) deactivators to Cu(I) activators. UV-vis spectra confirm the feasibility of the in situ SI-ATRP and indicate that the thickness and density of polymer brushes play an important role in performing a successful ATRP on GLM nanodroplets surfaces. Homo- and block copolymers, poly(3-sulfopropyl methacrylate potassium salt) (PSPMA) and poly((2-dimethylamino)ethyl methacrylate-b-(3-sulfopropyl methacrylate potassium salt)) P(DMAEMA-b-SPMA) are successfully grafted to the GLM nanodroplets. Polymer brushes modified GLM nanodroplets show potential applications such as friction reduction and oil-water emulsion separation. GLM nanodroplets mediated SI-ATRP provides a novel and robust approach to preparing multifunctional GLM nanodroplets for different applications.


Vitamin interdependencies predicted by metagenomics-informed network analyses and validated in microbial community microcosms.
Metagenomic or metabarcoding data are often used to predict microbial interactions in complex communities, but these predictions are rarely explored experimentally. Here, we use an organism abundance correlation network to investigate factors that control community organization in mine tailings-derived laboratory microbial consortia grown under dozens of conditions. The network is overlaid with metagenomic information about functional capacities to generate testable hypotheses. We develop a metric to predict the importance of each node within its local network environments relative to correlated vitamin auxotrophs, and predict that a Variovorax species is a hub as an important source of thiamine. Quantification of thiamine during the growth of Variovorax in minimal media show high levels of thiamine production, up to 100 mg/L. A few of the correlated thiamine auxotrophs are predicted to produce pantothenate, which we show is required for growth of Variovorax, supporting that a subset of vitamin-dependent interactions are mutualistic. A Cryptococcus yeast produces the B-vitamin pantothenate, and co-culturing with Variovorax leads to a 90-130-fold fitness increase for both organisms. Our study demonstrates the predictive power of metagenome-informed, microbial consortia-based network analyses for identifying microbial interactions that underpin the structure and functioning of microbial communities.


Development of magnesium-based biodegradable metals with dietary trace element germanium as orthopaedic implant applications.
From the perspective of element biosafety and dietetics, the ideal alloying elements for magnesium should be those which are essential to or naturally presented in human body. Element germanium is a unique metalloid in the carbon group, chemically similar to its group neighbors, Si and Sn. It is a dietary trace element that naturally presents in human body. Physiological role of Ge is still unanswered, but it might be necessary to ensure normal functioning of the body. In present study, novel magnesium alloys with dietary trace element Ge were developed. Feasibility of those alloys to be used as orthopaedic implant applications was systematically evaluated. Mg-Ge alloys consisted of α-Mg matrix and eutectic phases (α-Mg + Mg2Ge). Mechanical properties of Mg-Ge alloys were comparable to current Mg-Ca, Mg-Zn and Mg-Sr biodegradable metals. As-rolled Mg-3Ge alloy exhibited outstanding corrosion resistance in vitro (0.02 mm/y, electrochemical) with decent corrosion rate in vivo (0.6 mm/y, in rabbit tibia). New bone could directly lay down onto the implant and grew along its surface. After 3 months, bone and implant were closely integrated, indicating well osseointegration being obtained. Generally, this is a pioneering study on the in vitro and in vivo performances of novel Mg-Ge based biodegradable metals, and will benefit the future development of this alloy system. The ideal alloying elements for magnesium-based biodegradable metals should be those which are essential to or naturally presented in human body. Element germanium is a unique metalloid in the carbon group. It is a dietary trace element that naturally presents in human body. In present study, feasibility of Mg-Ge alloys to be utilized as orthopedic applications was systematically investigated, mainly focusing on the microstructure, mechanical property, corrosion behavior and biocompatibility. Our findings showed that Mg-3Ge alloy exhibited superior corrosion resistance to current Mg-Ca, Mg-Zn and Mg-Sr alloys with favorable biocompatibility. This is a pioneering study on the in vitro &in vivo performances of Mg-Ge biodegradable metals, and will benefit the future development of this alloy system.


The Ancestral Shape of the Access Proton Path of Mitochondrial ATP Synthases Revealed by a Split Subunit-a.
The passage of protons across membranes through F1Fo-ATP synthases spins their rotors and drives the synthesis of ATP. While the principle of torque generation by proton transfer is known, the mechanisms and routes of proton access and release and their evolution are not fully understood. Here, we show that the entry site and path of protons in the lumenal half channel of mitochondrial ATP synthases are largely defined by a short N-terminal α-helix of subunit-a. In Trypanosoma brucei and other Euglenozoa, the α-helix is part of another polypeptide chain that is a product of subunit-a gene fragmentation. This α-helix and other elements forming the proton pathway are widely conserved across eukaryotes and in Alphaproteobacteria, the closest extant relatives of mitochondria, but not in other bacteria. The α-helix blocks one of two proton routes found in Escherichia coli, resulting in a single proton entry site in mitochondrial and alphaproteobacterial ATP synthases. Thus, the shape of the access half channel predates eukaryotes and originated in the lineage from which mitochondria evolved by endosymbiosis.


Calibration of the ERG photostimulus with standard photometer and photodiode.
A method for quantifying the ERG photostimulus is presented. The units of measure are reasonably straightforward and yet consistent with laws of photochemistry and psychophysics. Application of these laws facilitates measurement with readily available photometric instrumentation.


A Case Report of a Severe, Unusually Delayed Anaphylactoid Reaction to Intravenous N-Acetylcysteine During Treatment of Acute Acetaminophen Toxicity in an Adolescent.
Anaphylactoid reactions are well-documented adverse events associated with the intravenous administration of N-acetylcysteine (NAC) in patients with acetaminophen overdose. Most reactions are mild, occurring within the first 1-5 hours of initiation. This report presents the case of an adolescent with a delayed, life-threatening anaphylactoid reaction 24.5 hours after starting NAC, where discontinuing NAC could have resulted in fulminant hepatic failure (FHF) and death. A 17-year-old previously healthy female presented with nausea, vomiting, and abdominal pain 10 hours after an acute acetaminophen ingestion. Her 11-hour serum acetaminophen concentration was above the treatment line (149 μg/mL), and she had elevated transaminases (AST = 202 U/L, ALT = 284 U/L). She was treated with intravenous NAC, which was suspended for 3 hours after she developed an apparent life-threatening anaphylactoid reaction with angioedema and respiratory distress 24.5 hours after treatment initiation. Given her high risk of progression to FHF, NAC was resumed at double the previous rate along with scheduled corticosteroids and antihistamines after resolution of her symptoms. Her AST increased to 10,927 U/L, and INR peaked at 3.6, but she had no further anaphylactoid symptoms. She was discharged in her normal state of health after 6 days. Discontinuing NAC in this case of severe, delayed anaphylactoid reaction could have resulted in FHF requiring liver transplant. The reason for her reaction is unclear but could be related to patient risk factors or medication error. Guidelines for reinitiation of NAC after development of delayed anaphylactoid reactions are not well-established. Close observation beyond the first 1-5 hours of NAC administration is warranted.


Lobular carcinoma in situ of the breast. An approach to rational treatment.
A review of 3299 benign breast lesions was carried out. Lobular carcinoma in situ (LCIs) was discovered in 52 cases; and of these, 44 had been treated by biopsy alone. During the follow-up period averaging 15.9 years, 11 patients developed invasive breast cancer (IBC): 9 ipsilateral lesions, and 4 contralateral. This was about 12 times the frequency expected. The development of IBC had no relation to the patient's age, nor could any correlation be drawn between the time periods which elapsed from the time of the diagnosis of the in situ cancer to the development of IBC. The ipsilateral occurrence of IBC was not isgnificantly different from the contralateral. Careful lifelong follow-up seems to be the rational treatment for women whose breast biopsy shows LCIs.


Integrating clinical staging and phenomenological psychopathology to add depth, nuance, and utility to clinical phenotyping: a heuristic challenge.
Psychiatry has witnessed a new wave of approaches to clinical phenotyping and the study of psychopathology, including the US National Institute of Mental Health's Research Domain Criteria, clinical staging, network approaches, the Hierarchical Taxonomy of Psychopathology, the general psychopathology factor, and a revival of interest in phenomenological psychopathology. The question naturally emerges about what the relationship between these new approaches is. Are they mutually exclusive and competing approaches, or can they be integrated in some way and be used to enrich each other? In this Personal View, we propose a possible integration between clinical staging and phenomenological psychopathology. Domains identified in phenomenological psychopathology (eg, selfhood, embodiment, and affectivity) can be overlaid on clinical stages to enrich and deepen the phenotypes captured in clinical staging (creating high-resolution clinical phenotypes). This approach might be useful both ideographically and nomothetically, to complement diagnosis, enrich clinical formulation, inform treatment of individual patients, and help to guide aetiology research, prediction of clinical trajectory and treatment. Overlaying phenomenological domains on clinical stages might require reformulating these domains in dimensional rather than categorial terms. This integrative project requires assessment tools (some of which are already available) that are sufficiently sensitive and thorough to pick up on the range of relevant psychopathology. The proposed approach offers opportunities for mutual enrichment: clinical staging might be enriched by introducing greater depth to phenotypes; phenomenological psychopathology might be enriched by introducing stages of severity and disorder progression to phenomenological analysis.


Developmental transcriptional regulation by SUMOylation, an evolving field.
SUMOylation is a reversible post-translational protein modification that affects the intracellular localization, stability, activity, and interactions of its protein targets. The SUMOylation pathway influences several nuclear and cytoplasmic processes. The expression of many genes, in particular those involved in development is finely tuned in space and time by several groups of proteins. There is growing evidence that transcriptional regulation mechanisms involve direct SUMOylation of transcriptional-related proteins such as initiation and elongation factors, and subunits of chromatin modifier and remodeling complexes originally described as members of the trithorax and Polycomb groups in Drosophila. Therefore, it is being unveiled that SUMOylation has a role in both, gene silencing and gene activation mechanisms. The goal of this review is to discuss the information on how SUMO modification in components of these multi-subunit complexes may have an effect in genome architecture and function and, therefore, in the regulation of gene expression in time and space.


Isolation of cardiac myofibrils and myosin light chains with in vivo levels of light chain phosphorylation.
Conditions are described for the preparation of functional myofibrils and myosin light chains from freeze-clamped beating hearts with the state of light chain phosphorylation chemically 'frozen' during the extraction procedure. Myofibrils were shown to be functionally intact by measurement of Ca2+ binding and ATPase activity. Highly purified cardiac myosin light chains could be routinely isolated from myofibrillar preparations using ethanol fractionation together with ion-exchange chromatography. Analysis of light chains for covalent phosphate indicated that basal levels of phosphorylation of the 18--20 000 dalton light chain of myosin in rabbit hearts beating in situ or in a perfusion apparatus were 0.3--0.4 mol/mol. Covalent phosphate content of the light chain fraction did not change during perfusion of hearts with 10 microM epinephrine.


Fatigue, anxiety and depression overrule the role of oncological treatment in predicting self-reported health complaints in women with breast cancer compared to healthy controls.
Women with breast cancer often attribute their health problems as side effects caused by oncological treatments. The aim of the study was to examine and compare self-reported health complaints (SHC) in postmenopausal patients with breast cancer to healthy controls. Women with breast cancer (N = 196) filled in 5 questionnaires 1-2 years after surgery; SHC Inventory, Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES), Fatigue - Functional Assessment of Cancer Therapy-Fatigue subscale (FACIT-F), Fatigue Visual Analog Scale (Fatigue VAS), and Hospital Anxiety and Depression Scale (HADS). Controls comprised 101 blood donors who reported on the questionnaires except for HADS. Bonferroni adjustment and p < 0.0017 was considered statistically significant for SHC Inventory, p < 0.05 for the remaining questionnaires. The patients, mean age 58.0 (SD 9.5), reported significantly more self-reported health complaints, whereof 6 of 29 complaints were significantly elevated compared to the controls, mean age 57.0 (SD 5.8) (p < 0.001). HADS scores in patients fell into normal range, mean 6.3 (SD 5.7). A subgroup of 48 patients experienced more frequent and severe symptoms in all the questionnaires compared to the remaining 148 patients, and the 101 controls. Among the patients, fatigue, anxiety and depression explained 49% of the total variance in self-reported health complaints (p ≤ 0.001). Most women with breast cancer (76%) reported health complaints equal to the healthy controls. Fatigue, anxiety and depression, not oncological treatments, were significant predictors for the complaints.


Untangling the web: mechanisms underlying ER network formation.
The ER is a continuous membrane system consisting of the nuclear envelope, flat sheets often studded with ribosomes, and a polygonal network of highly-curved tubules extending throughout the cell. Although protein and lipid biosynthesis, protein modification, vesicular transport, Ca(2+)dynamics, and protein quality control have been investigated in great detail, mechanisms that generate the distinctive architecture of the ER have been uncovered only recently. Several protein families including the reticulons and REEPs/DP1/Yop1p harbor hydrophobic hairpin domains that shape high-curvature ER tubules and mediate intramembrane protein interactions. Members of the atlastin/RHD3/Sey1p family of dynamin-related GTPases interact with the ER-shaping proteins and mediate the formation of three-way junctions responsible for the polygonal structure of the tubular ER network, with Lunapark proteins acting antagonistically. Additional classes of tubular ER proteins including some REEPs and the M1 spastin ATPase interact with the microtubule cytoskeleton. Flat ER sheets possess a different complement of proteins such as p180, CLIMP-63 and kinectin implicated in shaping, cisternal stacking and cytoskeletal interactions. The ER is also in constant motion, and numerous signaling pathways as well as interactions among cytoskeletal elements, the plasma membrane, and organelles cooperate to position and shape the ER dynamically. Finally, many proteins involved in shaping the ER network are mutated in the most common forms of hereditary spastic paraplegia, indicating a particular importance for proper ER morphology and distribution in large, highly-polarized cells such as neurons. This article is part of a Special Issue entitled: Functional and structural diversity of endoplasmic reticulum.


Assessing Adult Patients with Facial Deformities for Injectable Treatment: Do Current Classification Systems and Methodologies Meet Important Patient Needs?
Many individuals are affected by facial deformities. Injectable aesthetic treatments can often be used to improve appearance and/or dynamic function. However, to best meet the needs of these patients, broadly applicable methodologies are required for classifying the deformity, assessing severity, and developing a treatment strategy. To assess whether any published systems could be used for this purpose. Thirty-eight searches were conducted in PubMed (1999-2019; in English). Forty-two publications were identified describing novel classification systems for adult facial deformity. They were analyzed against a checklist of 10 characteristics defining an "optimal" system-based on appropriate anatomical coverage, wide usability across types of deformity, user-friendliness, applicable underlying methodology, and ability to guide treatment with injectables. None of the systems met more than 7 of the 10 checklist criteria; none were usable across multiple types of deformity or provided a recommendation for treatment with injectables. There remains a need for a broadly applicable system for classifying adult facial deformities ahead of injectable therapy. The checklist provides a developmental framework. With the increasing popularity and accessibility of injectables, this diverse and complex demographic is at risk of mismanagement without superior methods for devising treatment strategies.


Molecular phylogeny of all human enterovirus serotypes based on comparison of sequences at the 5' end of the region encoding VP2.
Sixty-six human enterovirus serotypes have been described using antibody neutralization, with antigenic variants defined within several serotypes. Despite the availability of sequence data for numerous enteroviruses, the molecular basis of serotype is unknown. Previous studies by others have identified four major phylogenetic groups within the human enteroviruses, but there has been no complete database of homologous sequences for all human enterovirus serotypes. We have determined the homologous partial VP2 sequences for the 12 prototype strains for which VP2 sequence was unavailable and for eight well-characterized antigenic variants. Phylogenetic analysis of all prototype strains produced four major groups, consistent with published enterovirus phylogenies. Many antigenic variants, however, failed to cluster with their respective prototype strains, suggesting that this portion of VP2 may be inappropriate for consistent molecular inference of serotype and for detailed study of enterovirus evolution.


Bioinspired structural transition of synthetic polymers through biomolecular ligand binding.
Inspired by ligand binding-triggered structural transition of biopolymers in living systems, we demonstrated the structural transition of thermoresponsive poly(N-isopropylacrylamide) through specific ligand binding of artificially evolved peptides to the polymer.


Biomechanical Considerations of Patching Material for Posterior Scleral Reinforcement Surgery.
To characterize biomechanical properties of genipin-crosslinked human dura mater as reinforcing material for posterior scleral reinforcement (PSR) and to compare it with crosslinked human sclera. Donor dura mater and sclera were crosslinked in the same optimized genipin solution. Resistance to enzyme degradation for both materials were investigated by exposing the materials to accelerated enzyme degrading. Elastic modulus and tensile strength were measured by biomechanics testing equipment. Crosslinked human dura mater was used as reinforcing patch in PSR on 57 adult pathologic myopic eyes. The patients were followed up for an average 3 years. The main outcome was eye globe axial length change and safety profile of the reinforcing material. Crosslinked dura mater demonstrated similar percentage weight loss to crosslinked sclera when exposed to enzymatic solution. Dura mater has higher density than sclera. The retaining elastic modulus after enzyme exposure was 72.02 MPa for crosslinked dura mater while 53.88 MPa for crosslinked sclera, 34% greater for crosslinked dura mater, P = 0.0186). At the end of 3 years follow-up, the mean globe axis of the surgery eyes was reduced by 1.29 mm (from 30.81 to 29.51 mm, P < 0.0001, paired t-test). Visual acuity (BCVA logMar) improved by 0.10 logMar unit which is an improvement of five letters (P = 0.0184, paired t-test). No material specific complication was noted. Crosslinked human dura mater may be superior to crosslinked human sclera as reinforcing material for PSR to manage progression of high myopia. This material was well tolerated on human eye.


Melatonin protects against ketorolac induced gastric mucosal toxic injuries through molecular mechanism associated with the modulation of Arylakylamine N-Acetyltransferase (AANAT) activity.
Ketorolac tromethamine (KT), is a widely used non-steroidal anti-inflammatory drug (NSAID) for treating moderate to severe pain. However, the use of KT has been restricted due to its highly toxic attributes that lead to severe gastric ulceration and bleeding. The protective effects of exogenous melatonin (MT) has been reported in conditions associated with gastro-intestinal disorders. This study aims at exploring the role of gastric endogenous MT level and it's metabolizing enzyme AANAT, at the onset of ketorolac mediated toxicities in the gastric mucosa. Gastric mucosal damage was induced in experimental rats by oral administration of graded doses of KT, where 50 mg/kg b.w. of KT was observed to incur maximum gastric lesions. However, gastric damages were found to be protected in rats, pre-treated with 60 mg/kg b.w. of MT. Post-sacrifice, mean ulcer index, oxidative status, total melatonin levels and enzyme activities associated with MT biosynthesis and catabolism were estimated. The results reveal that KT decreases AANAT activity with a concomitant decline in endogenous MT level which cumulatively aggravates gastric toxicity. Moreover, exogenous MT administration has been found to be protective in ameliorating this ulcerogenic process in rats, challenged with KT. Biochemical and histo-pathological observations revealed the reduction in oxidative stress level and replenishment of depleted gastric MT levels in MT pre-treated animals, which might be the causative factors in conferring protection to the gastric tissues and residing mitochondria. The results revealed a correlation between depleted gastric MT level and ulcer formation, which unveiled a novel ulcerogenic mechanism. This may bring forth future therapeutic relevance for treating patients suffering from KT mediated acute gastric toxicities.


Background-free imaging of luminescent nanodiamonds using external magnetic field for contrast enhancement.
We demonstrate a way of contrast increasing in wide-field optical images of diamond nanocrystals containing nitrogen-vacancy (NV) centers surrounded by an autofluorescing material, as in the case of intercellular imaging. Subtraction of an image taken in the presence of an external magnetic field of about 25 mT from an image of the same area measured when the field was absent eliminates the background and enhances the contrast because luminescence of the NV centers decreases in the presence of the field while the auto luminescence is not affected.


Chiropractic care of a pediatric patient with myasthenia gravis.
To describe the chiropractic care of a pediatric patient with complaints associated with myasthenia gravis. Clinical features A 2-year-old girl was provided chiropractic care at the request and consent of her parents for complaints of ptosis and generalized muscle weakness (ie, lethargy), particularly in the lower extremities. Prior to entry into chiropractic management, magnetic resonance imaging of the brain and acetylcholine receptor antibody tests were performed with negative results. However, the Tensilon test was positive and the diagnosis of myasthenia gravis was made by a pediatrician and seconded by a medical neurologist. Intervention and outcome The patient was cared for with contact-specific, high-velocity, low-amplitude adjustments to sites of vertebral subluxation complexes in the upper cervical and sacral spine. The patient's response to care was positive and after 5 months of regular chiropractic treatment her symptoms abated completely. There are indications that patients suffering from disorders "beyond low back pain" as presented in this case report may derive benefits from chiropractic intervention/management.


Plasma homovanillic acid in neuroleptic responsive and nonresponsive schizophrenics.
Changes in plasma homovanillic acid (HVA) were investigated in neuroleptic responsive and nonresponsive schizophrenics in order to delineate parameters of dopamine regulation, which may underlie differences in neuroleptic responsivity. Nineteen schizophrenics were treated with haloperidol for 6 weeks. HVA was sampled at baseline, 24 hr after initial neuroleptic dose, and after 6 weeks of treatment. Subjects were pretreated with debrisoquin in order to reduce the peripheral production of HVA. The responders had an initial rise in HVA at 24 hr after first neuroleptic dose, followed by a decline back to baseline over the 6 weeks of treatment. The nonresponders' HVA failed to rise at 24 hr after first neuroleptic dose. At 6 weeks of treatment their HVA had fallen to significantly below baseline. Thus, a rise in HVA 24 hr after the first dose of neuroleptic predicted treatment response; a fall in HVA at 6 weeks to below pretreatment values was associated with neuroleptic nonresponse.


Magnesium bioactive glass hybrid functionalized polyetheretherketone with immunomodulatory function to guide cell fate and bone regeneration.
Polyetheretherketone (PEEK) is being increasingly recognized as a highly promising polymer implant in orthopaedics due to its advantageous biocompatibility, favorable processability, and radiation resistance. Nonetheless, the long-term application of PEEK implants in vivo faces challenges due to unfavorable post-implantation inflammatory and immune reactions, which result in suboptimal osseointegration rates. Hence, biofunctionalizing the surface of PEEK implants emerges as a viable strategy to enhance osseointegration and increase the success rate. In this study, we developed a multifunctional PEEK implant through the in-situ incorporation of chitosan-coated bioactive glass nanoparticles (BGNs). This approach can impart immunomodulatory properties and enhance the potential for osseointegration. The resulting biofunctionalized PEEK material exhibited multiple beneficial effects. For instance, it facilitated M2 phenotypic polarization of macrophages, diminished the expression of inflammatory factors, and enhanced the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. Moreover, it exhibited an improved capacity for osseointegration when tested in vivo. The findings of the experiment highlighted the pivotal and complex role of the biofunctionalized PEEK implant in maintaining typical bone immunity and metabolism. The study proposes that the application of chitosan-BGNs presents a straightforward approach to developing multifunctional implants with the ability to promote biomineralization and immunomodulation, specifically tailored for orthopaedic applications.


Vectorization of Nucleic Acids for Therapeutic Approach: Tutorial Review.
Oligonucleotides present a high therapeutic potential for a wide variety of diseases. However, their clinical development is limited by their degradation by nucleases and their poor blood circulation time. Depending on the administration mode and the cellular target, these macromolecules will have to cross the vascular endothelium, to diffuse through the extracellular matrix, to be transported through the cell membrane, and finally to reach the cytoplasm. To overcome these physiological barriers, many strategies have been developed. Here, we review different methods of DNA vectorization, discuss limitations and advantages of the various vectors, and provide new perspectives for future development.


Unusual presentation of thyrotoxicosis as bradycardia, acute renal failure and hyperuricemia in an elderly patient.
Bradycardia with renal system involvement in patients with thyrotoxicosis has rarely been reported. We report a 72-year-old woman with unusual presentations of sinus bradycardia and normothermia accompanied by acute renal failure and hyperuricemia in thyrotoxicosis. The electrocardiogram changes in this patient included sinus bradycardia (50 beats per minute), followed by atrial fibrillation (84 beats per minute), and finally sinus rhythm with T wave inversion (80 beats per minute). Her renal function and hyperuricemia completely recovered after appropriate antithyroid therapy. A high index of suspicion is needed for early diagnosis and antithyroid treatment in patients with unusual manifestations of thyrotoxicosis in general clinical practice.


Calorimetric evidence for allosteric subunit interactions associated with inhibitor binding to band 3 transporter.
A calorimetric endotherm occurring at 68 degrees C (the C-transition) has been assigned previously to the integral domain of band 3 and was shown to be shifted to 78 degrees C after covalent binding of 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS). In this study, we correlate the fractional appearance of the shifted C-transition with the fraction of DIDS bound to the band 3 monomer population. Our results show a distinctly nonlinear correlation plot with the appearance of the shifted C-transition lagging behind DIDS labeling of the band 3 monomer population. The lag suggests that both monomers of a band 3 dimer must be labeled by DIDS in order for the shifted C-transition to appear at 78 degrees C, implying that the thermal unfolding of the integral domain of band 3 is modulated by allosteric interactions between subunits. This is the first in situ structural evidence supporting ligand-mediated subunit interactions within a "carrier"-type transporter protein oligomer.


A Mechanistic Model for Predicting the Physical Stability of Amorphous Solid Dispersions.
In this paper, we establish a mechanistic model for the prediction of amorphous solid dispersion (ASD) stability. The novel approach incorporates fundamental physical parameters, principally supersaturation, diffusivity, and interfacial energy, to model crystallization in ASDs accounting for both kinetic and thermodynamic drivers. API dependent decoupling coefficients were also considered which allowed dynamic mechanical analysis to probe molecular mobility, with viscosity measurements, across an exceptionally broad range of temperatures to support ASD stability simulations. ASDs are multicomponent systems in which the amorphous form of active pharmaceutical ingredients (APIs) are molecularly dispersed within a carrier. This gives rise to a transiently supersaturated API solution upon dissolution which increases the driving force for oral absorption and results in increased bioavailability as compared to that of the crystalline API. A major shortcoming of ASDs, however, is that there is the potential for amorphous APIs to revert to their more stable crystalline form during storage, despite the use of polymer carriers to stabilize formulations and limit recrystallization. Hot melt extrusion (HME) has been employed as the preparation method for ASDs used in this study as it is well-suited for the formation of uniform dispersions. The ASDs were stored under controlled temperature conditions, in the absence of humidity, to determine recrystallization kinetics. Our mechanistic model, considering both crystal nucleation and growth processes, describes temporal ASD stability through a system of coupled differential equations that connect the physiochemical properties of the ASD system to drug recrystallization. The model and prolonged time scale of crystallization observed highlight the importance of considering both thermodynamic and kinetic factors in the preparation of stable ASDs. Experimental observations were found to be in good agreement with predictions of the model confirming its utility in predicting the temporal physical stability of amorphous solid dispersions through a mechanistic lens.


Plastic bending in a semiconducting coordination polymer crystal enabled by delamination.
Coordination polymers (CPs) are a class of crystalline solids that are considered brittle, due to the dominance of directional coordination bonding, which limits their utility in flexible electronics and wearable devices. Hence, engineering plasticity into functional CPs is of great importance. Here, we report plastic bending of a semiconducting CP crystal, Cu-Trz (Trz = 1,2,3-triazolate), that originates from delamination facilitated by the discrete bonding interactions along different crystallographic directions in the lattice. The coexistence of strong coordination bonds and weak supramolecular interactions, together with the unique molecular packing, are the structural features that enable the mechanical flexibility and anisotropic response. The spatially resolved analysis of short-range molecular forces reveals that the strong coordination bonds, and the adaptive C-H···π and Cu···Cu interactions, synergistically lead to the delamination of the local structures and consequently the associated mechanical bending. The proposed delamination mechanism offers a versatile tool for designing the plasticity of CPs and other molecular crystals.


Type A Aortic Dissection Occurring After Previous Cardiac Surgery.
We retrospectively reviewed our experience of total arch replacement in patients undergoing repair of an ascending aortic dissection following previous cardiac surgery. Data were collected for patients with acute type A aortic dissection following previous cardiac surgery between January 2005 and December 2014. Clinical and prognostic features were retrospectively analyzed. Twenty-eight eligible patients (nonelective: 10, elective: 18) were identified. There was a mean period of 44.5 months between the first operation and the subsequent surgery. The overall 30-day mortality rate was 21.4%; 30.0% for nonelective patients and 16.7% for elective patients. Postoperative morbidity rate was higher among nonelective patients versus elective group. During follow-up, two patients died: one from intracranial hemorrhage and the other from a noncardiac cause. One patient received endografting as a result of the true lumen being compressed by the false lumen following aortic repair. When hemodynamically stable, patients with acute ascending aortic dissection following previous cardiac surgery may have improved outcomes if the surgery can be performed on an elective basis.


Core biopsies can be used to distinguish differences in expression profiling by cDNA microarrays.
The primary focus of this work was to determine the feasibility of obtaining representative expression array profiles from clinical core biopsies. For this purpose we performed six 16-gauge needle core biopsies and an excision biopsy on each of two different human xenografts, one from an Ewing's sarcoma cell line and the second from neuroblastoma cell line grown in Beige-Scid mice. Three of the six core biopsies were processed separately and the remaining three were pooled and processed together. As the initial RNA material isolated from the core biopsies was not sufficient for microarray analysis, an amplification procedure using a modified Eberwine protocol was performed, and the amplified products applied onto a 6000-feature human cDNA microarray. Comparisons of the array results from core biopsies (amplified RNA) and surgical specimens (non-amplified RNA) showed maintenance of the expression profile as assessed by hierarchical clustering. Gene expression profiles obtained from microarray analysis clearly differentiated the Ewing's sarcoma from the neuroblastoma with both core and excisional biopsies as starting material. Pooling the core biopsies did not improve the concordance with excisional biopsies. In conclusion, our results suggest that core biopsies can be used as a suitable and reliable material for the determination of tumor genetic profiles.


Angiogenic Potential of Multipotent Stromal Cells from the Umbilical Cord: an In Vitro Study.
The mechanisms of proangiogenic activity of multipotent stromal cells from human umbilical cord were analyzed in vitro. The absence of secreted forms of proangiogenic growth factor VEGF-A in the culture medium conditioned by umbilical cord-derived multipotent stromal cells was shown by ELISA. However, the possibility of paracrine stimulation of cell proliferation, mobility, and directed migration of endothelial EA.hy926 cells was demonstrated by using MTT test, Transwell system, and monolayer wound modeling. The capacity of multipotent stromal cells to acquire the phenotype of endothelium-like cells was analyzed using differentiation media of three types. It was found that VEGF-A is an essential but not sufficient inductor of differentiation of umbilical cord-derived multipotent stromal cells into CD31+ cells.


Survival after surgical treatment of breast cancer.
The principle objective of locoregional treatment in breast cancer is to eradicate local disease in the breast and local lymph nodes. Surgery in breast cancer provides locoregional control of the disease by resection appropriate to oncological principles, i.e. complete resection with tumour-free margins. Type and extent of breast surgery is dependent on tumour stage; beyond that and even more importantly, prognosis of an individual patient depends upon its stage at diagnosis. We reviewed the current literature, working out stage-specific survival and disease-free survival (DFS). The reported data were considered, according to stage and type of surgery, and a clear survey up to 20 years after surgery was depicted. Additionally, we assessed quality of life after breast cancer surgery. Overall survival (OS) rates after 5 years range from 93-84% in women diagnosed with stage I disease to 18% in women diagnosed with stage IV disease. In the management of stages I and II breast cancer, breast conservation with lumpectomy and radiation is a preferable alternative to mastectomy, with equivalent patient outcome. In stages III and IV breast cancer, surgery allows local control of the disease, but prognosis depends predominantly on the response to systemic treatment, as does prognosis in all breast cancer patients. The reported data distributing patients outcome according to stage and surgical treatment provide a clear summary in order to estimate an individual patient's risk.


The Role of Image-guided Radiotherapy in the Treatment of Anorectal Cancer Using Prone Belly-board Positioning.
To evaluate Radiation Therapy Oncology Group planning target volume margins of 7-10 mm for radiation therapy in anorectal cancer using prone belly-board positioning without image guidance. 375 kV cone beam computed tomography image-guided radiotherapy (IGRT) images from 20 patients treated for anorectal cancer were retrospectively analyzed for setup shifts. We calculated the total translational shift for each patient and the frequency with which setup shifts exceeded 7 mm and 10 mm. A total of 42.7% of treatments required shifts >7 mm and 20.8% >10 mm. The mean translational shift was 7.1 mm. 70% of patients experienced shifts ≥7 mm in 20% or more of their treatments and 25% of ≥10 mm in 20% or more of their treatments; 15% experienced shifts ≥10 mm in over half of their treatments. van Herk calculations suggest margins of 12.8 mm are necessary for accuracy without IGRT. IGRT using a prone belly board and 7-10 mm margins requires daily image-guidance to prevent planning target volume misses and ensure optimal dose delivery.


The relationship of subtle differences in fasting serum triglycerides with subtle differences in the electrocardiogram: a study of the PR interval.
The nonmedical community has long recognized the well-observed fact that both medical and nonmedical matters can be expressed in gradations. Witness the continuum from hot to cold, from mad to glad, from fat to thin as but a few simple confirmations. In contrast, the medical establishment, by act if not by word, still struggles to establish absolutes. This is well-exemplified by such diagnoses as diabetes mellitus or no diabetes mellitus even though common sense would suggest that there must be degrees of this metabolic problem (possibly 21 or 32 percent diabetes mellitus). This report underlines the presence and importance of degrees of lipid metabolism versus degrees of electrocardiopathy. Additionally, this experiment suggest that such relationships become more meaningful as one focuses onto the subtleties of such a relationship.


Frequency of low molecular weight IgM in human cord blood.
Thirty cord blood sera from healthy neonates and five sera from still-born infants (two with suspected infections and high IgM) were assessed for the presence of low molecular weight (LMW) IgM using two independent sensitive techniques, viz. filtration chromatography and immunoblotting. The first technique revealed this LMW moiety in 4 of 22 sera, all from healthy full-term infants, and it constituted 4-25% of the total IgM. LMW IgM was not found in any of the 30 sera using the immunoblotting technique or in 15 healthy adult sera, but was found consistently in rheumatoid sera used as positive controls.


Endoscopic Urethroplasty Using Buccal Graft for Male Membranous Urethral Stricture.
To demonstrate a new minimally invasive endoscopic approach to urethroplasty. The procedure was performed in a male patient with prior history of prostate cancer managed by radiation who subsequently developed an 8 mm flow-limiting membranous urethral stricture. After stricture dilation a 1 cm wide strip of superficial mucosa was resected from the bladder neck past the area of stricture, creating a bed for the graft to lay. Buccal mucosa graft was harvested in standard fashion. With the graft outside the urethra and using the RD 180 endoscopic suturing device, a suture is placed in the proximal end of the graft, then through the bladder neck, and back through the graft. As the suture is pulled, the pulley phenomenon advances the graft into place on the bladder neck. The graft is then anchored to the posterior urethra with secure straps. A catheter is placed to hold the graft flat during the healing process. The procedure lasted 2.5 hours without any complications. Estimated blood loss was 50cc, and the patient was discharged after the procedure. Catheter was removed at 4weeks. Cystoscopy at 10weeks post-op showed good graft viability, with peak flow improving to 20 mL/s compared to 4 mL/s preoperatively. At 6months, he continues to do well without evidence of recurrent urethral stricture. Endoscopic urethroplasty using buccal graft appears to offer a safe and effective repair option for management of ureteral strictures.


Crystal structure of Li3Ga(BO3)2.
The crystal structure of trilithium gallium bis-(orthoborate), Li3Ga(BO3)2, is isotypic with Li3Al(BO3)2 in a triclinic cell in space-group type P-1. The three Li and the unique Ga atom are coordinated by four O atoms each in tetra-hedra, and the two B atoms are coordinated by three O atoms in orthoborate triangles. Chains with composition [Ga2(BO3)4]6- extend along the a axis. The Li atoms inter-leave these chains in tetra-hedral inter-stices. A comparison is made between the structure model of the title compound and that of a previously reported model for a compound with the same composition [Abdullaev & Mamedov (1972 ▸). Zh. Strukt. Khim. 13, 943-946.].


Treatment of movement disorders in dystonia-choreoathtosis cerebral palsy.
Symptomatic treatment of cerebral palsy (CP) is difficult, with variable beneficial effect. The choice of therapy is guided by the main clinical features (spasticity, dystonia/choreoathetosis), by the experience of experts, and by the results of open-label trials and a few controlled studies. Treatments of spasticity are not discussed in depth here. From open-label trials and a few controlled studies in dystonia/choreoathetosis CP, it appears that treatment should be started at a low dose and increased slowly, and that more beneficial effects are obtained on upper extremity function, face and jaw dystonia and drooling, and in children. L-Baclofen or antiepileptic drugs are rarely effective and poorly tolerated whereas benzodiazepines may be moderately helpful. Local injections of botulinum toxin help to reduce pain and limit the amplitude of some movements (violent neck movements with high risk of symptomatic radiculomyelopathy). In a rare subtype of dystonia-choreathetosis CP with little spasticity and MRI lesions, bilateral pallidal stimulation (GPi) has shown mild to moderate improvement of dystonia (in open-label small series and in one controlled study) with no cognitive or mood adverse effects. Optimal placement of the leads was a major (but not exclusive) factor for good outcome but results cannot be predicted on an individual basis and larger studies are needed.


Irradiation biology of male brown marmorated stink bugs: is there scope for the sterile insect technique?
Brown marmorated stink bugs, Halyomorpha halys Stål (Hemiptera: Pentatomidae), are regularly intercepted, but there are few eradication tools. Currently, no sterile insect technique program exists for Hemiptera. Adult males were irradiated at 4-60 Gy, mated and their progeny reared for two generations, with mortality assessed at F1 egg, F1 adult and F2 egg stages. The F1 eggs showed a dose response to irradiation between 4 and 36 Gy, with 97% sterility at 16 Gy, and higher doses producing complete egg mortality. Only rare F1 survivors had progeny, but the F2 generation showed identical responses between maternal and paternal lines; most egg batches showed either very low or very high mortality. Irradiation with 16 Gy resulted in 98.5% sterility, cumulative over F1 and F2. Lack of a dose response at the F2 generation precludes the use of irradiation-induced inherited sterility. The conventional sterile insect technique appears possible by irradiation of males from ∼12 to 16 Gy. The effect of radiation dose on females is not known, thus we cannot conclude whether bi-sex release is feasible so for now the release of males only is recommended. More work is needed on the competitive fitness of irradiated males, and logistics such as mass rearing or field collection, in order to determine the feasibility of the approach.


"Baby on board": Reducing risk taking in adult drivers in a simulated driving game.
Two studies examined the effects of different socio-affective factors on risk driving behaviour. In Experiment 1, 87 adult drivers we asked to play a computer-based driving game after being exposed to a series of images that depicted infants, police or neutral information (control condition). In Experiment 2 we tested a further 60 adult drivers. We found a significant effect of our manipulation on driving behaviour, with performance being significantly less risky in the infant condition than in the police and control conditions. In addition, this advantage was not simply due to variations in emotions typically associated with infant pictures. The results of this study highlight the importance of studying the role of socio-affective context when investigating factors that influence driving behaviour.


Supplemental dietary phytosterin protects against 4-nitrophenol-induced oxidative stress and apoptosis in rat testes.
4-Nitrophenol (PNP), is generally regarded as an environmental endocrine disruptor (EED). Phytosterin (PS), a new feed additive, possesses highly efficient antioxidant activities. The transcription factor, nuclear factor-erythroid 2-related factor 2 (Nrf2), is an important regulator of cellular oxidative stress. Using rats, this study examined PNP-induced testicular oxidative damage and PS-mediated protection against that damage. The generation of MDA and H2O2 upon PNP and PS treatment was milder than that upon treatment with PNP alone. This mitigation was accompanied by partially reversed changes in SOD, CAT, GSH and GSH-Px. Moreover, PNP significantly reduced the caudal epididymal sperm counts and serum testosterone levels. Typical morphological changes were also observed in the testes of PNP-treated animals. PNP reduced the transcriptional level of Nrf2, as evaluated by RT-PCR, but it promoted the dissociation from the Nrf2 complex, stabilization and translocation into the nucleus, as evaluated by immunohistochemistry and Western blotting. In addition, PNP enhanced the Nrf2-dependent gene expression of heme oxygenase-1 (HO-1) and glutamate-cysteine ligase catalytic subunit (GCLC). These results suggest that the Nrf2 pathway plays an important role in PNP-induced oxidative damage and that PS possesses modulatory effects on PNP-induced oxidative damage in rat testes.


EAAT1 variants associated with glaucoma.
Glaucoma is one of the leading causes of blindness characterized by progressive loss of retinal ganglion cells (RGCs) and their axons. We reported that glutamate/aspartate transporter (GLAST) knockout mice showed progressive RGC loss and optic nerve degeneration that are similar to glaucoma. To explore the possibility that rare variants in the EAAT1 gene (the human homolog of GLAST) cause susceptibility to glaucoma, we performed targeted sequencing of EAAT1 in 440 patients with glaucoma and 450 control subjects. We identified 8 rare variants in 20 out of 440 patients, including 4 synonymous and 4 missense variants located at protein coding regions. One of these rare variants (rs117295512) showed significant association with the risk of glaucoma (OR = 10.44, P = 0.005). Furthermore, the allele frequency for loss-of-function EAAT1 variants, pAla169Gly and pAla329Thr, was 5.5 folds higher in the glaucoma (1.1%) compared with the control cohort (0.2%). These findings suggest that these rare variants may contribute to the pathogenesis of glaucoma and that loss-of-function variants in EAAT1 are present in a small number of patients with glaucoma.


Health improvements of older adults based on benefit duration: Lessons from Korean social pension policies.
The social pension, introduced in 2008 in Korea, has now become the most prominent old age income for most older adults. As of May 2022, it paid a monthly benefit of around USD 275 for 6.0 million older persons aged 65 and over who belong to the bottom 70% of the income and asset distribution. Although social pension's objectives focus on alleviating old age poverty and increasing income levels, it also encompasses a clear implication on health: social pension benefit can be spent on items or activities that improve the beneficiary's health. Using the Korean Longitudinal Study on Ageing data, between 2006 and 2018, and the Propensity Score Matching combined with Generalized Difference-In-Differences based on event study design, this study investigates the effects of receiving the social pension on objective measures of health that are representative of health and well-being in old age, by benefit duration. Study results showed that continually receiving social pension significantly improved beneficiaries' grip strength and cognitive ability. Grip strength was improved by 2.3-kg in the fifth year of receiving social pension. Additionally, the cognitive ability (K-MMSE score) was improved by 1.309 points in the first year. Results of descriptive analysis suggested that the social pension may have benefitted the health of the beneficiaries by improving their nutrition, health care utilization, and physical activities, and reducing financial strain and associated stress level. To the best of our knowledge, this is the first study to investigate the cumulative effects of nation-wide social pension programs on older adults' objective health measures by benefit duration up to five years, in a high-income country setting where old age income security systems are under-developed.


Human infections caused by Staphylococcus argenteus in Germany: genetic characterisation and clinical implications of novel species designation.
We report a series of Staphylococcus argenteus infections from Saarland, Germany. Travel histories were unremarkable for extra-European sojourns, indicating an autochthonous transmission mode. Multilocus sequence typing revealed that all isolates were members of the clonal complex CC2250. In only one case, guideline-adherent treatment with an isoxazolyl penicillin was prescribed. Our report illustrates the perils of novel species designations, which may lead to misconceptions and suboptimal treatment choices among clinicians.


Measurement of Metabolome Samples Using Liquid Chromatography-Mass Spectrometry, Data Acquisition, and Processing.
We present a protocol for metabolomic sample measurement using hydrophilic interaction chromatography (HILIC) combined with high-resolution Orbitrap mass spectrometry (MS). We also introduce a raw data processing method using MZmine 2 software, and include a list of 111 metabolite peaks (with their m/z values and retention times) previously identified in metabolome samples using this method.


General Practitioners' Empathy and Health Outcomes: A Prospective Observational Study of Consultations in Areas of High and Low Deprivation.
We set out to compare patients' expectations, consultation characteristics, and outcomes in areas of high and low socioeconomic deprivation, and to examine whether the same factors predict better outcomes in both settings. Six hundred fifty-nine patients attending 47 general practitioners in high- and low-deprivation areas of Scotland participated. We assessed patients' expectations of involvement in decision making immediately before the consultation and patients' perceptions of their general practitioners' empathy immediately after. Consultations were video recorded and analyzed for verbal and non-verbal physician behaviors. Symptom severity and related well-being were measured at baseline and 1 month post-consultation. Consultation factors predicting better outcomes at 1 month were identified using backward selection methods. Patients in deprived areas had less desire for shared decision-making (P <.001). They had more problems to discuss (P = .01) within the same consultation time. Patients in deprived areas perceived their general practitioners (GPs) as less empathic (P = .02), and the physicians displayed verbal and nonverbal behaviors that were less patient centered. Outcomes were worse at 1 month in deprived than in affluent groups (70% response rate; P <.001). Perceived physician empathy predicted better outcomes in both groups. Patients' expectations, GPs' behaviors within the consultation, and health outcomes differ substantially between high- and low-deprivation areas. In both settings, patients' perceptions of the physicians' empathy predict health outcomes. These findings are discussed in the context of inequalities and the "inverse care law."


Early detection and prognosis prediction for colorectal cancer by circulating tumour DNA methylation haplotypes: A multicentre cohort study.
Early detection and prognosis prediction of colorectal cancer (CRC) can significantly reduce CRC-related mortality. Recently, circulating tumour DNA (ctDNA) methylation has shown good application foreground in the early detection and prognosis prediction of multiple tumours. This multicentre cohort study evaluated ctDNA methylation haplotype patterns based on archived plasma samples (collected between 2010 and 2018) from 1138 individuals at two medical centres: Fudan University Shanghai Cancer Center (Shanghai, China) and Southern Medical University Nanfang Hospital (Guangzhou, Guangdong, China), including 366 healthy individuals, 182 patients with advanced adenoma (AA), and 590 patients with CRC. Samples were processed using the ColonES assay, a targeted bisulfite sequencing method that detects ctDNA methylation haplotype patterns in 191 genomic regions. Among these 1138 samples, 748 were used to develop a classification model, and 390 served as a blinded cohort for independent validation. The study is registered at https://register.clinicaltrials.gov with the unique identifier NCT03737591. The model obtained from unblinded samples discriminated patients with CRC or AA from normal controls with high accuracy. In the blinded validation set, the ColonES assay achieved sensitivity values of 79.0% (95% confidence interval (CI), 66%-88%) in AA patients and 86.6% (95% CI, 81%-91%) in CRC patients with a specificity of 88.1% (95% CI, 81%-93%) in healthy individuals. The model area under the curve (AUC) for the blinded validation set was 0.903 for AA samples and 0.937 for CRC samples. Additionally, the prognosis of patients with high preoperative ctDNA methylation levels was worse than that of patients with low ctDNA methylation levels (p = 0.001 for relapse-free survival and p = 0.004 for overall survival). We successfully developed and validated an accurate, noninvasive detection method based on ctDNA methylation haplotype patterns that may enable early detection and prognosis prediction for CRC. The Grant of National Natural Science Foundation of China (No.81871958), National Natural Science Foundation of China (No. 82203215), Shanghai Science and Technology Committee (No. 19140902100), Scientific Research Fund of Fudan University (No.IDF159052), Shanghai Municipal Health Commission (SHWJRS 2021-99), and Shanghai Sailing Program (22YF1408800).


Beryllium-7 measurements of wind erosion on sloping fields in the wind-water erosion crisscross region on the Chinese Loess Plateau.
Soil erosion is complex in the wind-water erosion crisscross region of the Chinese Loess Plateau, as interleaving of wind and water erosion occurs on both temporal and spatial scales. It is difficult to distinguish wind erosion from the total erosion in previous studies due to the untraceable of aeolian particles and the limitation of feasible methods and techniques. This study used beryllium-7 measurements to study wind erosion in the wind-water erosion crisscross region on the Chinese Loess Plateau arms to delineate wind erosion distribution, to analyze its implication to erosive winds and surface microrelief, and to determine correlations between erosion rates and slope gradients. Results obtained using beryllium-7 measurements based on observation plots were verified with saltating particle collection method, and were also verified on a field scale. Results indicated that the effective resultant erosion wind was from northward, which was proved by the eight-directional distributed saltating particles. The microrelief of the ground surface contributed to the formation of high or low erosion centers. Wind erosion rates increased with a linear (R2≥0.95) or exponential (R2≥0.83) fitting increase in the slope gradients as reported in previous studies. Compared to wind erosion on field scale, both the plots and fields exhibited similar distribution patterns in wind erosion isolines. We also determined that the wind erosion rate for two fields estimated, based on equations developed from plot scale was acceptable. This study validates the feasibility of beryllium-7 measurements for soil-wind erosion field experiments and the potential to expand this approach to real field conditions.


Arsenic exposure from food exceeds that from drinking water in endemic area of Bihar, India.
Extensive evidence of elevated arsenic (As) in the food-chain, mainly rice, wheat and vegetables exists. Nevertheless, the importance of exposure from food towards total As exposure and associated health risks in areas with natural occurring As in drinking water is still often neglected, and accordingly mitigations are largely focused on drinking water only. In this study, the contribution of food over drinking water to overall As exposure was estimated for As exposed populations in Bihar, India. Increased lifetime cancer risk was predicted using probabilistic methods with input parameters based on detailed dietary assessment and estimation of As in drinking water, cooked rice, wheat flour and potato collected from 91 households covering 19 villages. Median total exposure was 0.83 μg/kgBW/day (5th and 95th percentiles were 0.21 and 11.1 μg/kgBW/day) and contribution of food (median = 49%) to overall exposure was almost equal to that from drinking water (median = 51%). More importantly and contrary to previous studies, food was found to contribute more than drinking water to As exposure, even when drinking water As was above the WHO provisional guide value of 10 μg/L. Median and 95th percentile excess lifetime cancer risks from food intake were 1.89 × 10-4 and 7.32 × 10-4 respectively when drinking water As was below 10 μg/L and 4.00 × 10-4 and 1.83 × 10-3 respectively when drinking water As was above 10 μg/L. Our results emphasise the importance of food related exposure in As-endemic areas, and, perhaps surprisingly, particularly in areas with high As concentrations in drinking water - this being partly ascribed to increases in food As due to cooking in high As water. These findings are timely to stress the importance of removing As from the food chain and not just drinking water in endemic areas.


Simple Diverting Colostomy for Sacral Pressure Ulcers: Not So Simple After All.
Surgeons are often asked to provide a diverting colostomy to enable healing or simplify management of sacral pressure ulcers. However, little evidence exists regarding the safety of a diversion in this often compromised patient population. We hypothesized that malnourished patients with sacral pressure ulcers have poor outcomes with fecal diversion. ACS-NSQIP (2012-2018) was used to identify patients who underwent elective diverting colostomy for sacral pressure ulcers. Demographics, comorbidities, and perioperative details were recorded. Postoperative complications and 30-day mortality were compared between patients with moderate/severe hypoalbuminemia (< 2.5 g/dL) vs those with albumin > 2.5 g/dL. We identified a total of 863 patients who underwent elective diverting colostomy for sacral pressure ulcer. Mean age was 57.5 years old. Rate of associated comorbidities was high, with most patients classified as ASA class 3 or 4. Over 40% of patients had a preoperative albumin level < 2.5 g/dL. Thirty-day overall postoperative mortality was 6.7%. This was significantly higher in patients with hypoalbuminemia (11.4% vs. 3.5%, p < 0.001). On multivariable regression analysis, preoperative albumin < 2.5 g/dL was independently associated with mortality (OR 1.92, p = 0.039). Other factors associated with mortality included increased age (OR 1.04 per year, p < 0.001), preoperative sepsis (OR 1.66, p = 0.003), and Black race (OR 2.2, p = 0.01). Diverting colostomy performed for patients with sacral pressure ulcers is associated with a substantial risk of postoperative death. Surgeons should carefully consider risks of diversion in this patient population, especially in malnourished patients with hypoalbuminemia.


Antifungal action and induction of resistance by β-aminobutyric acid against Penicillium digitatum to control green mold in orange fruit.
Green mold, caused by Penicillium digitatum, is the most economically important postharvest disease of orange fruit worldwide. The aim of this study was to evaluate the effect of β-aminobutyric acid (BABA) treatment on the inhibition of P. digitatum both in orange fruit and in vitro as well as the possible mechanisms of action. BABA at 125 mM significantly inhibited mycelial growth, spore germination, and germ tube elongation of P. digitatum by 93.3, 90.3, and 90.5%, respectively. The relative electrical conductivity of mycelium was increased for a period of 0-36 h after treated with BABA at 125 mM. Furthermore, BABA caused a high level of malondialdehyde (MDA) in P. digitatum mycelia during four days of incubation. The ergosterol content in the plasma membrane of P. digitatum was significantly lower in BABA-treated mycelia. Also, protein and sugar leakage were increased with BABA treatment compared with that in the control. Besides, BABA caused a considerable reduction in the total lipid content of P. digitatum mycelia at 125 mM. Scanning electron microscopy (SEM) of P. digitatum treated with BABA at 125 mM showed shrunken, distorted, and collapsed mycelia. The application of BABA at 125 mM in orange fruit inoculated with P. digitatum suppressed disease incidence and disease severity by 74.6 and 77.3%, respectively, compared to untreated fruit. Moreover, the activity of defense-related enzymes, including peroxidase (POD), polyphenoloxidase (PPO), and phenylalanine ammonia-lyase (PAL) were significantly enhanced in the orange fruit treated with BABA at 125 mM.


Controlling a spillover pathway with the molecular cork effect.
Spillover of reactants from one active site to another is important in heterogeneous catalysis and has recently been shown to enhance hydrogen storage in a variety of materials. The spillover of hydrogen is notoriously hard to detect or control. We report herein that the hydrogen spillover pathway on a Pd/Cu alloy can be controlled by reversible adsorption of a spectator molecule. Pd atoms in the Cu surface serve as hydrogen dissociation sites from which H atoms can spillover onto surrounding Cu regions. Selective adsorption of CO at these atomic Pd sites is shown to either prevent the uptake of hydrogen on, or inhibit its desorption from, the surface. In this way, the hydrogen coverage on the whole surface can be controlled by molecular adsorption at a minority site, which we term a 'molecular cork' effect. We show that the molecular cork effect is present during a surface catalysed hydrogenation reaction and illustrate how it can be used as a method for controlling uptake and release of hydrogen in a model storage system.


Detection of complex chromosome rearrangements using optical genome mapping.
Chromosomal structural variations (SVs) are a main cause of human genetic disease. Currently, karyotype, chromosomal microarray analysis (CMA), and fluorescent in situ hybridization (FISH) form the backbone of current routine diagnostics (CRD). These methods have their own limitations. CRD cannot identify cryptic balanced SVs and complex SVs even if these techniques were performed either simultaneously or in a sequential manner. Optical genome mapping (OGM) is a novel technology that can identify several classes of SVs with higher resolution, but studies on the applicability of OGM and its comparison with CRD are inadequate for difficult and complicated chromosomal SVs are lacking. Herein, seven patients with definite complicated SVs involving at least two breakpoints (BPs) were recruited for this study. The results of BPs and SVs from OGM were compared with those from CRD. The results showed that all BPs of five samples and partial BPs of two samples were detected by OGM. The undetected BPs were all close to the repeat-rich gap region. Besides, OGM also detected additional SVs including a cryptic balanced translocation, two additional complex chromosomal rearrangement (CCR). OGM yielded the additional information, such as the orientation of acentric fragments, BP positions, and genes mapped in the BP region for all the cases. The accuracy of additional SVs and BPs detected by OGM was verified by FISH panel and next-generation sequencing and Sanger sequencing. Taken together, OGM exhibit a better performance in detecting chromosomal SVs compared to the CRD. We suggested that OGM method should be utilized in the clinical examination to improve the efficiency and accuracy of genetic disease diagnosis, supplemented by FISH or karyotyping to compensate for the SVs in the repeat-rich gap region if necessary.


New media for culture to blastocyst.
To develop sequential media for extended culture of embryos in human IVF, with use of a mouse embryo assay. The BlastAssist system was developed. Blastocyst culture has been our routine method since 1994, using earlier media IVF and M3 in sequence. Experimental laboratory study. University Hospital and university research unit. F1 hybrids between CD1 female and BDF male mice. Two-cell mouse embryos were cultured 4 days in test media; 1 day in phase 1 medium followed by 3 days in phase 2 medium. Percentage of expanded and hatched blastocysts. Compared with a two-cell block in the old culture system, more than 80% went to the blastocyst stage in the new media. The new medium system was based on a heavily modified low-glucose Earle's balanced salt solution. Additions were pyruvate, lactate, amino acids, human serum albumin, and Synthetic Serum Replacement. In contrast to regular tissue culture cells, embryos required an increased concentration of EDTA. The final media produced a blastocyst frequency of 94% and a day 4 hatching frequency of 71%. With the high blastocyst frequency demonstrated here, the combination of blastocyst culture and single ET should be an effective means of treatment in patients and could help to eliminate multiple gestations. The BlastAssist system is commercially available.


Contamination artifact that mimics in-situ carcinoma on contrast-enhanced digital mammography.
Contrast-enhanced digital mammography (CEDM) is an advanced breast imaging technique using iodinated intravenous contrast to detect breast cancer. This article describes imaging features of a skin contamination artifact on CEDM that mimics in-situ carcinoma in a case series. Five patients were identified whose CEDM images demonstrated apparent calcifications and non-mass enhancement suspicious for in-situ carcinoma, with no subsequent evidence of disease. Retrospective image analysis was performed on the unprocessed image data, processed images, and imaging parameters. Dual-energy mammographic technique was performed on two breast phantoms with varying degrees of topical contrast contamination. Temporal analysis confirmed the suspicious finding was neither an abnormality of the compression paddle nor the receptor. Comparison of LE and HE images demonstrated the suspicious finding attenuated near the K-edge of iodine, suggesting contrast contamination. Iodinated contrast applied to the surface of breast phantoms replicated the artifact, with a pattern of apparent enhancement similar to the appearance of in-situ carcinoma. Skin contamination with iodinated contrast can result in an artifact on post-contrast digital mammography that mimics the appearance of in-situ carcinoma.


Nanomedicine in cancer therapy.
Cancer remains a highly lethal disease in the world. Currently, either conventional cancer therapies or modern immunotherapies are non-tumor-targeted therapeutic approaches that cannot accurately distinguish malignant cells from healthy ones, giving rise to multiple undesired side effects. Recent advances in nanotechnology, accompanied by our growing understanding of cancer biology and nano-bio interactions, have led to the development of a series of nanocarriers, which aim to improve the therapeutic efficacy while reducing off-target toxicity of the encapsulated anticancer agents through tumor tissue-, cell-, or organelle-specific targeting. However, the vast majority of nanocarriers do not possess hierarchical targeting capability, and their therapeutic indices are often compromised by either poor tumor accumulation, inefficient cellular internalization, or inaccurate subcellular localization. This Review outlines current and prospective strategies in the design of tumor tissue-, cell-, and organelle-targeted cancer nanomedicines, and highlights the latest progress in hierarchical targeting technologies that can dynamically integrate these three different stages of static tumor targeting to maximize therapeutic outcomes. Finally, we briefly discuss the current challenges and future opportunities for the clinical translation of cancer nanomedicines.


Evaluating the use of angiotensin-converting enzyme inhibitors for older nursing home residents with chronic heart failure.
Despite their well noted therapeutic benefits for heart failure (HF), angiotensin-converting enzyme (ACE) inhibitors may be underprescribed and underdosed among older nursing home patients. To assess the use of ACE inhibitor therapy in older (> or =70 years) nursing home residents with systolic heart failure (HF). A cross-sectional, retrospective analysis. Five long-term care facilities in Providence, Rhode Island. Adults aged 70 years or older with left ventricular (LV) ejection fractions < or =40%. New York Heart Association (NYHA) class, comorbid diseases, and cardiac medications with logistic regression analysis to clarify their bearing on the prescription of ACE inhibitors. Of the 819 nursing home residents who were evaluated, 119 (24 men, 95 women) fulfilled exacting entry criteria, i.e., heart failure signs/symptoms and documented LV systolic dysfunction. Forty-one of these 119 (35%) older persons were receiving ACE inhibitor therapy, predominantly in doses (< or =50 mg captopril/day or < or =5 mg enalapril/ day) less than those of proven therapeutic efficacy. Compared with older residents not receiving ACE inhibitors, those receiving ACE inhibitors included fewer with NYHA Class I HF (0 vs 21%, P = .017), more men (58 vs 28%, P< or =.01), and more people with hypertension (61 vs 35%, P< or =.01). In contrast, diuretics were prescribed more frequently among those not receiving ACE inhibitors (83 vs 56%, P< or =.001). ACE inhibitors are underprescribed and underdosed among elderly nursing home patients carefully screened to include systolic HF and no contraindications to the medication. ACE inhibitors are particularly underused in those elderly with NYHA Class I HF and in those receiving diuretics.


Diversity of adenosine deaminase in children with EBV-related diseases.
Adenosine deaminase (ADA) is an enzyme involved in purine metabolism with an important role in cellular immunity. Thus, this study investigated the association between ADA and Epstein-Barr virus (EBV)-related diseases. We retrospectively collected data from all children admitted to the Children's Hospital of Soochow University, Suzhou, China, between May 1, 2018, and March 31, 2019, who underwent plasma EBV-DNA polymerase chain reaction, alanine aminotransferase (ALT), and ADA testing. Of 6868 children, 1877 had an elevated level of ADA, and 4991 had a level within the normal range. Multivariate logistic regression analysis indicated that ALT (adjusted odds radio [aOR] = 1.001, 95% confidence interval [CI]: 1.001-1.002), EBV infection (aOR = 8.486, 95% CI: 6.753-10.663), inflammatory disease (aOR = 3.915, 95% CI: 3.198-4.794), autoimmune disease (aOR = 2.307, 95% CI: 1.823-2.920), and malignant disease (aOR = 1.381; 95% CI: 1.101-1.734) were risk factors for an elevated ADA level. Furthermore, the ADA levels among EBV-related diseases significantly differed, including infectious mononucleosis, atypical EBV infection, respiratory infection, malignant disease, and other diseases (P < 0.05). In addition, the ADA level positively correlated with the Epstein-Barr viral load (r = 0.501, P < 0.05). This large, retrospective study identified a correlation between ADA and EBV-related diseases, which may help clinicians detect these diseases earlier based on the plasma ADA concentration.


Evaluation of Carotid Intima Media Thickness and Renal Artery Resistive Index in Patients With Pseudoexfoliation Syndrome: A Prospective Case-Control Study.
To investigate the significance of renal artery resistance and carotid intima media thickness (CIMT) parameters in patients with pseudoexfoliation syndrome (PES). In this prospective case-control study, 37 patients were involved and grouped as PES (n=19) and control groups (n=18). Ophthalmological evaluation included visual acuity, intraocular pressure, central corneal thickness measurement, and optic disc evaluation. In addition, renal artery resistive index and CIMT measurements were taken for all patients and compared between the groups. The 2 groups were similar with respect to age, sex, and family history of glaucoma. The mean CIMT in the PES group was found to be significantly higher compared with the control group (0.73±0.02 vs. 0.59±0.06 mm, P=0.003). Renal artery resistive indices were found to be higher in the PES group than in the control group, however, the difference was not significant (P=0.46). A moderate positive correlation between CIMT and renal artery resistive indices was detected (r=0.447, P=0.01). However, a higher correlation rate was detected when the analysis was made in the PES group only (r=0.603, P=0.01). CIMT increases in PES patients and also the renal artery resistance index has a tendency to increase. Patients with PES should be informed about potential systemic consequences of this syndrome.


Cooked common beans (Phaseolus vulgaris) protect against β-cell damage in streptozotocin-induced diabetic rats.
Diabetes is a disease characterized by a hyperglycemic stage that leads to a chronic inflammatory state. We evaluated the in vivo effect of a diet supplemented with 25 % cooked black bean cultivar Negro 8025 (N8025) flour in streptozotocin-induced diabetic rats. The effect was assessed before (preventive-treatment) and after (treatment) the onset of diabetes. There is a significant decrease of total phenolic, tannins and anthocyanins content after cooking, and the concentration of most of the single phenols analyzed are only slightly decreased. The treatment group showed a significant reduction of glucose (22.8 %), triglycerides (21.9 %), total cholesterol (29.9 %) and LDL (56.1 %) that correlates with a protection of pancreatic ß-cells. The diet with N8025 flour before the induction of diabetes did not exert a protective effect (glucose levels are similar to the diabetic control) but they have low levels of total cholesterol (47.5 %) and LDL (56.1 %). The preventive-treatment group did not inhibit the increase of TNF-α and IL-1β, whereas the treatment group did, compared to the diabetic control. Therefore, N8025 bean supplementation can be recommended to control diabetes.


Muscarinic agonists cause calcium influx and calcium mobilization in forebrain neurons in vitro.
We have examined the effects of the muscarinic agonist carbachol on the intracellular free Ca2+ concentration ([Ca2+]i) in primary cultures of neurons from rat forebrain using the Ca2+-sensitive fluorescent dye fura-2. Addition of carbachol increased the [Ca2+]i in approximately 60% of cells studied. Oxotremorine-M, but not pilocarpine, mimicked the effects of carbachol. The response was reduced by 60% on removal of extracellular Ca2+, a finding suggesting that muscarinic receptor activation causes Ca2+ influx in addition to intracellular Ca2+ mobilization. Tetrodotoxin and nitrendipine also significantly reduced the response to carbachol. These studies suggest that the changes in [Ca2+]i produced by activation of muscarinic receptors result in part from mobilization of intracellular Ca2+ and that influx through voltage-sensitive Ca2+ channels also provides a significant contribution to the net [Ca2+]i change observed.


[Effect of captopril on arterial pressure, systemic hemodynamics and renin activity in the blood plasma of rats with spontaneous hypertension].
An angiotensin-I-converting enzyme, captopril, was administered since birth onward to normotensive (NR) and spontaneously hypertensive rats (SHR). It produced a marked hypotensive effect in SHR only. Cardiac output and circulating blood volume were similar in intact and experimental animals, NR and SHR alike. Captopril considerably increased plasma renin activity in NR and SHR.


On the Allylic Oxidation of Ent-kaurenic Acid Methyl Ester with Lead Tetra-acetate.
In this paper, results obtained upon treatment of the methyl ester of ent-kaur-16-en-19-oic acid (1b) with lead tetra-acetate under reflux in glacial acetic acid solution and an argon atmosphere are described. After 30 minutes reflux, GC-MS analysis of the product indicated the presence of three substances, the initial compound (1b, 7 %), the methyl ester of ent-kaur-16-en-15-O-acetyl-19-oic acid (2a, C₂₃H₃₀0₄, 45 %), and its isomer, the methyl ester of ent-kaur-15-en-17- 0-acetyl-19-oic acid (3a, 47 %). Flash chromatography over silica gel containing 20% AgNO₃ yielded 2b (456 mg), which was identified by direct comparison with an authentic sample, and 3a (472 mg), whose structure was established by uni- and bi-dimensional NMR analysis. Hydrolysis of 3a with dry ammonia in MeOH yielded the methyl ester of ent-kaur-15-en-17-hydroxy-19-oic acid (3b, C₂₁H₃₂ 0₃); treatment of this compound with chromic acid/pyridine complex rendered the aldehyde (4).


Air calorics: a technique and results.
A major problem with air calorics appears to be one of technique. A pilot study led to the design of irrigating tips which allow consistant air presentation and simultaneous measurements of irrigating temperature at the delivery orifice (adding a second sensor). Preset temperatures of 24 C and 50 C in our system yielded air equilibration mean temperatures of 27.4 C and 45 C at the delivery orifice during testing. A normal study was carried out at these temperatures with an air flow of six liters per minute for 60 seconds. The range of caloric responses, mean maximum speed, and standard deviation are comparable to values previously reported with water stimulations. Statistical testing indicated no difference between ears for either warm or cold. Also, there was no significant difference for warm versus cold responses. We have performed over 2000 clinical examinations that incorporate this technique with satisfactory results and remarkable acceptance by the patients. The normal or "standard" probe size has been found to be adequate for the majority of the clinic population.


Neural responses to induced emotion and response to social threat in intermittent explosive disorder.
Individuals with intermittent explosive disorder (IED) are reported to exhibit amygdala (AMYG) hyper-activation to anger faces during functional magnetic resonance imaging (fMRI). However, it remains unknown if emotional experience is different in study participants with IED compared with healthy controls (HC). Thus, we examined the comparative effect of pleasant and unpleasant IAPS pictures in IED and HC individuals. Eighty study participants (40 IED and 40 HC) underwent fMRI scanning while viewing blocks of angry and happy faces and while viewing blocks of pleasant and unpleasant pictures from the International Affective Picture System (IAPS). Compared with HC participants, IED participants exhibited greater AMYG responses to angry, but not happy, faces; IED and HC participants, however, did not differ in AMYG responses to pleasant or unpleasant IAPS pictures. There were no group differences in Orbital-Frontal Cortical (OFC) responses to emotional faces or IAPS pictures other than a significantly higher OFC response pleasant, compared with unpleasant, IAPS pictures. These findings suggest that, compared with healthy individuals, those with IED have a hypersensitive amygdala to social-emotional threat but that this characteristic does not extend to neural responses related to the experience of emotion in the context of the paradigms tested.


Stimulation of the dorsolateral prefrontal cortex modulates muscle sympathetic nerve activity and blood pressure in humans.
Muscle sympathetic nerve activity (MSNA) controls the diameter of arterioles in skeletalmuscle, contributing importantly to the beat-to-beat regulation of blood pressure (BP). Although brain imaging studies have shown that bursts of MSNA originate in the rostral ventrolateral medulla, other subcortical and cortical structures-including the dorsolateral prefrontal cortex (dlPFC)-contribute. We tested the hypothesis that MSNA and BP could be modulated by stimulating the dlPFC. dlPFC. In 22 individuals MSNA was recorded via microelectrodes inserted into the common peroneal nerve, together with continuous BP, electrocardiographic, and respiration.Stimulation of the right (n=22) or left dlPFC (n=10) was achieved using transcranial alternating current (tcACS; +2 to -2mA, 0.08 Hz,100 cycles), applied between the nasion and electrodes over the F3 or F4 EEG sites on the scalp. Sinusoidal stimulation of either dlPFC caused cyclicmodulation of MSNA, BP and heart rate, and a significant increase in BP. We have shown, for the first time, that tcACS of the dlPFC in awake humans causes partial entrainment of MSNA, heart rate and BP, arguing for an important role of this higher-level cortical area in the control of cardiovascular function.