Genetic Causes, Clinical Features, and Survival of Underlying Inborn Errors of Immunity in Omani Patients: a Single-Center Study.
Early identification of inborn errors of immunity (IEIs) is crucial due to the significant risk of morbidity and mortality. This study aimed to describe the genetic causes, clinical features, and survival rate of IEIs in Omani patients. A prospective study of all Omani patients evaluated for immunodeficiency was conducted over a 17-year period. Clinical features and diagnostic immunological findings were recorded. Targeted gene testing was performed in cases of obvious immunodeficiency. For cases with less conclusive phenotypes, a gene panel was performed, followed by whole-exome sequencing if necessary. A total of 185 patients were diagnosed with IEIs during the study period; of these, 60.5% were male. Mean ages at symptom onset and diagnosis were 30.0 and 50.5 months, respectively. Consanguinity and a family history of IEIs were present in 86.9% and 50.8%, respectively. Most patients presented with lower respiratory infections (65.9%), followed by growth and development manifestations (43.2%). Phagocytic defects were the most common cause of IEIs (31.9%), followed by combined immunodeficiency (21.1%). Overall, 109 of 132 patients (82.6%) who underwent genetic testing received a genetic diagnosis, while testing was inconclusive for the remaining 23 patients (17.4%). Among patients with established diagnoses, 37 genes and 44 variants were identified. Autosomal recessive inheritance was present in 81.7% of patients with gene defects. Several variants were novel. Intravenous immunoglobulin therapy was administered to 39.4% of patients and 21.6% received hematopoietic stem cell transplantation. The overall survival rate was 75.1%. This study highlights the genetic causes of IEIs in Omani patients. This information may help in the early identification and management of the disease, thereby improving survival and quality of life.


Calcium binding characteristics and structural changes of phosvitin.
Phosvitin is a unique highly phosphorylated protein that plays a role in the regulation of calcification. We conducted a comprehensive study of the chemical, thermodynamic and structural aspects of the interaction of phosvitin with calcium ions using a calcium ion selective electrode (ISE), isothermal titration calorimetry (ITC), circular dichroism spectrum (CD) and fluorescence spectroscopy, respectively. The results showed that under neutral and alkaline conditions, distinct high affinity and low affinity binding modes existed in the interaction between phosvitin and calcium. The high affinity association constant was approximately 10(4)mol(-1), while the binding sites contained nearly 30mol of calcium per mole of phosvitin. This reaction was driven by enthalpy. The unordered and β-turn conformations of phosvitin increased, while the β-sheet conformation decreased. The main interaction forces were electrostatic force, hydrogen bonds or van der Waals force. The low affinity association constant and binding sites were not constant, as many calcium ions were sequestered by phosvitin. The binding reaction was driven by entropy, and the β-sheet conformation of phosvitin increased while the unordered conformation decreased. The main interaction force was hydrophobic force. However, under acidic conditions, the interaction between phosvitin and calcium was an entropy-driven endothermic reaction, and the main interaction force was weak hydrophobic force. This calcium-binding characteristic of phosvitin may play a specific role in its biological function.


Use of Electronic Health Record Data for Drug Safety Signal Identification: A Scoping Review.
Pharmacovigilance programs protect patient health and safety by identifying adverse event signals through postmarketing surveillance of claims data and spontaneous reports. Electronic health records (EHRs) provide new opportunities to address limitations of traditional approaches and promote discovery-oriented pharmacovigilance. To evaluate the current state of EHR-based medication safety signal identification, we conducted a scoping literature review of studies aimed at identifying safety signals from routinely collected patient-level EHR data. We extracted information on study design, EHR data elements utilized, analytic methods employed, drugs and outcomes evaluated, and key statistical and data analysis choices. We identified 81 eligible studies. Disproportionality methods were the predominant analytic approach, followed by data mining and regression. Variability in study design makes direct comparisons difficult. Studies varied widely in terms of data, confounding adjustment, and statistical considerations. Despite broad interest in utilizing EHRs for safety signal identification, current efforts fail to leverage the full breadth and depth of available data or to rigorously control for confounding. The development of best practices and application of common data models would promote the expansion of EHR-based pharmacovigilance.


The effects of glucocorticosteroids on the chemiluminescence response of bovine phagocytic cells.
The effects of corticosteroids on the chemiluminescence response of bovine phagocytic cells were determined both in vitro and in vivo. The in vitro addition of hydrocortisone or dexamethasone had no significant effect on the chemiluminescence response of leukocytes in a whole blood or purified polymorphonuclear leukocyte (PMN) population. Cattle that received a single 20 mg dose of dexamethasone or three 20 mg doses of dexamethasone (given 24 hours apart) demonstrated the expected effects on the bovine leukogram (leukocytosis, neutrophilia, lymphopenia, eosinopenia, and monocytosis) and also demonstrated the expected suppressive effect on lymphocyte response to phytohemagglutinin (PHA). However, neither a single nor multiple dexamethasone treatment(s) had an effect on the chemiluminescence response of phagocytes in whole blood, but significantly enhanced the chemiluminescence response of the purified PMN leukocyte population. There was no significant difference between the two dexamethasone treatment groups in either the degree or duration of the effects observed in the chemiluminescence or lymphocyte response assays.


Nursing intervention to meet the family members' needs during the surgery waiting time.
to assess the effect of a care intervention focused on meeting the needs of family members of surgical patients during the surgery waiting time, when compared to conventional care. a study with a quasi-experimental design that was developed from December 2019 to February 2020 and included 313 family members (Intervention Group=149 and Control Group=164) from a private hospital. The intervention consisted in four moments: "knowing the surgical environment and process", "information when the surgery starts", "information when the surgery ends", and "family-patient reunion". The "satisfaction" variable was assessed through the "Patient Satisfaction with Nursing Care Quality Questionnaire" instrument. The data were analyzed using descriptive and analytical statistics. The study observed the ethical principles in research. the family members in the Intervention Group presented greater satisfaction with Nursing care, 90.07(9.8), when compared to the Comparison Group, 78.72(16.38), with an 11.35-point increase(p=0.000). the results showed that the families that received the intervention on the patient's status during the surgery waiting time were more satisfied with Nursing care in comparison to the conventional intervention.


An Interdisciplinary Approach to Metastatic Pancreatic Cancer and Comorbid Opioid Use Disorder Treatment Within a VA Health Care System.
A multidisciplinary approach provided safe and feasible cancer treatment in a patient with advanced pancreatic cancer and coexisting active substance use disorder.


[Treatment of cervical cancer in the Republic of Srpska].
Since 1897, when the first radical hysterectomy with lymphadenectomy was done by Wertheim in Vienna, this operation has had the central role in the surgical treatment of invasive cervical tumors. In the period from 1997 to 2010, 177 patients diagnosed with invasive cervical cancer according to the International Federation of Gynecology and Obstetrics (FIGO) stage IB1 - II were operated at the Department of Obstetrics and Gynecology in Banja Luka. All patients underwent radical hysterectomy by Wertheim - Meigs. The aim of this study is to present the technique of this operation, as well as its effectiveness in the treatment of cervical cancer. The distribution of the patients having invasive cervical cancer according to the International Federation of Gynecology and Obstetrics classification was as follows: I B1 - 35.67%, I B2 - 23.17%, II A - 15.48%, II B - 25.68% on average is 21.3 removed lymph glands. The rate of intraoperative and postoperative complications was 8 (4.51%) and 17 (9.60%), respectively. Of the 26 patients who were operated in the period from 2005 - 2010, 13 had stage II B according to the International Federation of Gynecology and Obstetrics; there were 6 lethal outcomes (23.08) and the five-year survival rate was 76.92%. By applying the proper surgical technique and early prevention of immediate complications, we achieved satisfactory results in operative morbity and mortality, intraoperative and postoperative complications of the lesion for radical surgery by the Wertheim-Meigs-in the treatment of cancer of the uterus in the I B - II B stage according to the International Federation of Gynecology and Obstetrics classification.


Inheritance and expression of a sex-linked enzyme in the frog, Rana clamitans.
The pattern of inheritance indicates that the gene for aconitase-1 is sex linked in the frog. Rana clamitans, and that the male is the heterogametic sex. Unlike mammals, both male and female frogs carry and express two alleles for this sex-linked gene. Therefore, the sex chromosomes in these frogs and probably others behave like an autosomal pair, with one homologue carrying a male-determining element.


Necrotizing soft-tissue infections.
A variety of infections are encountered by the practicing surgeon. Uncommonly, a patient presents with minimal external manifestations of a deep surgical soft-tissue infection. Early aggressive intervention is required to minimize the morbidity in these often debilitated patients.


HIV Care Experiences During the COVID-19 Pandemic: Mixed-Methods Telephone Interviews with Clinic-Enrolled HIV-Infected Adults in Uganda.
COVID-19 measures that restrict movement may negatively impact access to HIV care and treatment. To contribute to the currently limited evidence, we used telephone interviews with quantitative and qualitative questions to examine how clients perceived COVID-19 and its effect on their HIV care and ART adherence. One hundred (n = 100) Ugandan adults on ART from an existing study were randomly selected and enrolled. Interviews were recorded, transcribed, and analyzed using descriptive statistics and rapid content analyses. 76% of clients indicated that COVID-19 negatively impacted travel to HIV clinics; 54% perceived that coming to the clinic increased their risk of acquiring COVID-19; and 14% said that COVID-19 had negatively impacted their ART adherence. Qualitative feedback suggests that fear of COVID-19 infection discouraged clinic attendance while stay-at-home orders helped routinize ART adherence and employ new community-based approaches for HIV care. Addressing negative unintended consequences of COVID-19 lockdowns on HIV care is urgently needed.


National estimates of cancer prevalence in China, 2011.
Little is known about the nationwide cancer prevalence in China. This paper aimed at assessing the 5-year cancer prevalence in China for 25 major cancers. Incidence data were estimated using data from 177 cancer registries and covering 175 million populations. Survival data were from 17 cancer registries diagnosed during 2003-2005 and followed up until 31 December 2010. Standardized protocols for data collection and validation were adopted. Cancer prevalence for 25 major sites was estimated from year-specific incidence rates and survival probabilities according to standardized formula. The estimated 5-year prevalence for all cancers combined in 2011 in China was 7.49 million (3.68 million for men and 3.81 million for women). Cancer prevalence estimates for 5 years varied by cancer sites, ranging from 11,900 for testicular cancer to 1.02 million for women breast cancer. Those most prevalent five cancers (breast, colorectal, lung, stomach and esophageal cancers) covered 56.1% of cancer burden in China. The proportion for the 5-year prevalence was higher in urban areas compared to rural areas (666 per 100,000 versus 440 per 100,000), while cancer prevalence estimates were higher for women compared to men, with the men/women ratio of 5-year cancer prevalence reaching 0.96. This paper provides the first systematic analysis on 5-year cancer prevalence for 25 major cancers in China in 2011, which may serve as a baseline for assessment of the overall effectiveness of cancer health care. The huge number of cancer survivors requires resource allocation to improve health care programs and primary prevention, especially in rural areas.


Technical report: A low cost technique for vessel sizing in angioplasty.
Vessel measurement in angiography is important for balloon and stent sizing. The most accurate techniques involve calibrating the angiographic image with a catheter with radioopaque markers, but these are expensive. A new method of vessel sizing for angioplasty and stenting is described: the guidewire is moved within the vessel through a set distance, and this movement is shown by digital subtraction. Testing with phantoms shows this to be simple, accurate and reproducible.


Botulinum C2 toxin ADP-ribosylates cytoplasmic beta/gamma-actin in arginine 177.
Isolated cytoplasmic actin of human platelet and pig liver actin, but not rabbit skeletal muscle actin, was ADP-ribosylated by botulinum C2 toxin in the presence of [32P]NAD. Tryptic digestion of the [32P]ADP-ribosylated platelet actin generated two labeled peptides: a soluble peptide covering residues 174-183 and an insoluble fragment containing residues 148-183. Further digestion of these two peptides with thermolysin yielded the same radioactive peptide, which was in both cases peptide 175-177. Amino acid sequence analysis of peptides 174-183 and 175-177 located the ADP-ribosylation on Arg177.


Reversal of androgenic alopecia by minoxidil: lack of effect of simultaneously administered intermediate doses of cyproterone acetate.
A male volunteer with frontal alopecia was treated simultaneously with 20 mg cyproterone acetate and 5 mg minoxidil topically (daily). During treatment with both drugs, new hair growth was observed on the alopecic scalp. The new hair was lost after discontinuing minoxidil treatment, although cyproterone acetate treatment was continued.


Display of somatostatin-related peptides in the complementarity determining regions of an antibody light chain.
Peptide display in antibody complementarity determining regions (CDRs) offers several advantages over other peptide display systems including the potential to graft heterologous peptide sequences into multiple positions in the same backbone molecule. Despite the presence of six CDRs in an antibody variable domain, the majority of insertions reported have been made in heavy chain CDR3 (h-CDR3) which may be explained in part by the highly variable length and sequence diversity found in h-CDR3 in native antibodies. The ability to graft peptide sequences into CDRs is restricted by amino acids in these loops that make structural contacts to framework regions or are oriented towards the hydrophobic interior and are important for the proper folding of the antibody. To identify such positions in human kappa-light chain CDR1 (kappa-CDR1) and CDR2 (kappa-CDR2), we performed alignments of 1330 kappa-light chain variable region amino acid sequences and 19 variable region X-ray crystal structures. From analyses of these alignments, we predict insertion points where sequences can be grafted into kappa-CDR1 and kappa-CDR2 to prepare synthetic antibody molecules. We then tested these predictions by inserting somatostatin and somatostatin-related sequences into kappa-CDR1 and kappa-CDR2, and analyzing the expression and ability of the modified antibodies to bind to membranes containing somatostatin receptor 5. These results expand the repertoire of CDRs that can be used for the display of heterologous peptides in the CDRs of antibodies.


Suppression of dioxins in waste incinerator emissions by recirculating SO2.
Sulphur is an effective inhibitor of the formation of Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-furans (PCDD/Fs), as was proven in laboratory and pilot plant studies. In this study, a pilot-scale system with capacity 300 N m(3) h(-1) was situated at the bypass of an actual hazardous waste incinerator (HWI) and tested to reduce the emission of PCDD/Fs. Activated carbon was used as a medium to adsorb SO2 from flue gas and release it again at the higher temperature of filtered ash detoxification to achieve SO2 circulation in the system. Most PCDD/Fs in the filtered ash are decomposed by thermal treatment. Experimental results indicate that the system is capable of stable operation with SO2 accumulation at a high level of concentration and a high reduction efficiency of PCDD/Fs. A reduction of more than 80% was already achieved without addition of other sulphur compounds. When pyrite (FeS2) was added the reduction of PCDD/Fs could reach 94%, with a residual PCDD/Fs concentration in the flue gas as low as 0.13 ng TEQ N m(-3). This SO2 recirculating and suppression technology potentially provides significant progress for dioxin emission control in waste incineration and could be useful for controlling emissions of PCDD/Fs and other chlorinated organic chemicals in China.


Deep Brain Stimulation of the Interposed Cerebellar Nuclei in a Conditional Genetic Mouse Model with Dystonia.
Dystonia is a neurological disease that is currently ranked as the third most common motor disorder. Patients exhibit repetitive and sometimes sustained muscle contractions that cause limb and body twisting and abnormal postures that impair movement. Deep brain stimulation (DBS) of the basal ganglia and thalamus can be used to improve motor function when other treatment options fail. Recently, the cerebellum has garnered interest as a DBS target for treating dystonia and other motor disorders. Here, we describe a procedure for targeting DBS electrodes to the interposed cerebellar nuclei to correct motor dysfunction in a mouse model with dystonia. Targeting cerebellar outflow pathways with neuromodulation opens new possibilities for using the expansive connectivity of the cerebellum to treat motor and non-motor diseases.


The Comaneci Device for Entering an Acute-Angled Small Feeder during Cerebral Arteriovenous Malformation Embolization: A Novel Technique to Support Microcatheterization.
In this report, we describe the use of the Comaneci device to support microcatheterization in a small branch arising from a parent artery during embolization. In 2 cases, arteriovenous malformations presented with intracranial hemorrhage. A microcatheter was navigated into a small feeder while the Comaneci device was deployed just distal to the feeder with an acute angle from the parent artery. Our technical note represents an alternative option of catheterization in cases with difficult access to small feeders originating from higher flow arteries at a sharp angle while maintaining continuous flow in the parent artery.


Marijuana and immunity: tetrahydrocannabinol-mediated inhibition of growth and phagocytic activity of the murine macrophage cell line, P388D1.
The effects of delta-9-tetrahydrocannabinol (THC) on the growth, DNA synthesis and phagocytic activity of P388D1, a murine macrophage cell line, were investigated. Incubating cell cultures with THC resulted in a dose-dependent inhibition of cell propagation and DNA synthesis. The magnitude of these effects was dependent upon the number of cells in the culture as well as the protein content in the culture medium. As the cell number increased, the THC effect decreased. Using cell cultures in which the cell concentration was standardized, THC (greater than or equal to 5 micrograms/ml) produced pronounced inhibitions of cell growth and DNA synthesis, while lower THC concentrations (less than or equal to 3 micrograms/ml) were less effective. Studies examining the phagocytic activity of the P388D1 cells indicating exposure to THC (5 micrograms/ml for 2 h) only marginally affected the association of latex beads with the external surface of the plasma membrane. However, the ability of these THC-treated cells to internalize the latex particles was severely depressed. Thus, the data indicate that THC inhibited the growth and functional activity of murine macrophages in vitro and suggests that the P388D1 cell line is a useful model to study the effects of cannabinoids on the phagocytic process.


Penicillin Allergy Impact and Management.
There is international evidence that penicillin allergies are associated with inferior prescribing and patient outcomes. A host of tools now exist from assessment (risk assessment tools, clinical decision rules) to delabeling (the removal of a beta-lactam allergy via testing or medical reconciliation) to reduce the impact of these "labels" in the hospital and community setting, as a primary antimicrobial stewardship intervention.


Prognostic differences between atrial fibrillation and atrial flutter.
This report presents the outcome of a cohort of 94 patients with atrial fibrillation from the Canadian Registry of Atrial Fibrillation, in which we paid particular attention to the probability of stroke and death. We also evaluated warfarin use over time and compared left atrial dimensions in patients with atrial flutter with those with atrial fibrillation.


Robotic Radical Cystectomy in the Contemporary Management of Bladder Cancer.
"The robotic approach for radical cystectomy has become increasingly adopted by the urologic oncology community, as it has been shown to have equivalent oncologic outcomes with shorter hospital stay and fewer perioperative transfusions. Consensus guidelines from expert surgeons have been published to provide guidance on all aspects of how to implement the robotic approach in the urologic oncology clinic."


Assignment of the human 2',3'-cyclic nucleotide 3'-phosphohydrolase gene to chromosome 17.
2',3'-Cyclic nucleotide 3'-phosphohydrolase (CNP) has been used as a general oligodendrocyte and Schwann cell marker enzyme within the nervous system and has been the intense target of a number of recent studies. In this report, we determined the chromosomal localization of the human CNP gene using PCR on two somatic cell DNA panels. PCR amplification, using four primer pairs across an intron, confirms that the CNP gene is localized to chromosome 17. We also present the complete intron sequence of the human gene usd to make the assignment. This intron contains a c----t polymorphism located at nucleotide 1215, which may be of use in mapping the CNPase gene more precisely within chromosome 17.


Nitrous oxide emissions in response to straw incorporation is regulated by historical fertilization.
The incorporation of crop straw with fertilization is beneficial for soil carbon sequestration and cropland fertility improvement. Yet, relatively little is known about how fertilization regulates the emissions of the greenhouse gas nitrous oxide (N2O) in response to straw incorporation, particularly in soils subjected to long-term fertilization regimes. Herein, the arable soil subjected to a 31-year history of five inorganic or organic fertilizer regimes (unfertilized; chemical fertilizer application, NPK; 200% NPK application, 2 × NPK; manure application, M; NPK plus manure application, NPKM) was incubated with and without rice straw to evaluate how historical fertilization influences the impact of straw addition on N2O emissions. The results showed that compared to the unfertilized treatment, historical fertilization strongly increased N2O emissions by 0.48- to 34-fold, resulting from increased contents of hot water-extracted organic carbon (HWEOC), NO3-, and available phosphorus (Olsen-P). Straw addition had little impact on N2O emission from the unfertilized and NPK treatments, primarily due to Olsen-P limitation. In contrast, straw addition increased N2O emissions by 102-316% from the 2 × NPK, M, and NPKM treatments as compared to the corresponding straw-unamended treatments. These results indicated that N2O emissions in response to straw addition were largely regulated by historical fertilization. The N2O emissions were closely associated with the depletion of NO3- and decoupled from change in NH4+ content, suggesting that NO3- was the main substrate for N2O production upon straw addition. The stoichiometric ratios of HWEOC to mineral N and mineral N to Olsen-P were key factors affecting N2O emissions, underscoring the importance of resource stoichiometry in regulating N2O emissions. In conclusion, historical fertilization largely regulated the impacts of crop straw incorporation on N2O emissions via shifts in NO3- depletion and the stoichiometry of HWEOC, mineral N, and Olsen-P.


Early Pleistocene Lynx issiodorensis (Felidae, Carnivora) from the Taurida Cave, Crimea.
The cranial and mandibular remains of two adult individuals of Lynx issiodorensis (Croizet et Jobert, 1828) are described from the Early Pleistocene locality of the Taurida cave (Crimea, Late Villafranchian, 1.8-1.5 Ma). This lynx species was a typical representative of the Villafranchian fauna of the Eastern Mediterranean. A high craniological variability of L. issiodorensis is noted.


The genes encoding light-harvesting subunits of Cyclotella cryptica (Bacillariophyceae) constitute a complex and heterogeneous family.
Total RNA was isolated from the diatom Cyclotella cryptica and separated into poly(A)+ and poly(A)- fractions. These fractions were subjected to in vitro translation/immunoprecipitation experiments using an antiserum directed against the predominant light-harvesting complex of Cy. cryptica (ccry antiserum) and a heterologous antiserum raised against the light-harvesting complex of the cryptophyte Cryptomonas maculata (cmac antiserum). From translation reactions programmed with poly(A)+ RNA the ccry-antiserum immunoprecipitated polypeptides with relative molecular weights (Mr) of 27000, 25000, 23000 and 21000, while the cmac-antiserum precipitated proteins with Mrs of 32500 and 27000, respectively. Subsequent cDNA synthesis and immunological screening of the cDNA library with both antisera resulted in the isolation of six cDNA clones encoding light-harvesting subunits. Full-length precursors were 199-210 amino acids in length and had Mrs of 20000-23000. The lengths of the putative signal peptides were 29 or 30 amino acids. Pairwise comparison revealed that the similarity between the clones ranged from 54-99% on the nucleotide level and from 36-99% at the amino acid level. In agreement with the data from the screens with the two antisera, the genes clustered into two groups. The data provide evidence that the genes constitute a heterogeneous multigene family and that the light-harvesting system of Cy. cryptica might be as complex as that of higher plants and green algae.


The interaction of cobalt (II) complexes with bovine apocarbonic anhydrase B.
The second-order rate constants for interaction of a number of cobalt(II) complexes (including the aquated ion) with bovine apocarbonic anhydrase have been measured at pH equal to 7.5, 25 degrees C and I equal 0.1 M. The ease of entry of cobalt decreases, in general, as the number of its coordinated watersdecreases. The highest complexes (bis or tris) do not react. The Mono cobalt(II) -8-quinolinol-5-sulfonate and, particularly, 8-quinolinol complexes react very much more rapidly with apoenzyme than does Co(H20)6-2+ ion. The results are discussed.


Reduction in microtubule dynamics in vitro by brain microtubule-associated proteins and by a microtubule-associated protein-2 second repeated sequence analogue.
Microtubule-associated protein (MAP) binding to assembled microtubules (MTs) can be reduced by the addition of polyglutamate without significant MT depolymerization or interference with MT elongation reactions. Ensuing polymer length redistribution in MAP-depleted MTs occurs on a time scale characteristic of that observed with MAP-free MTs. The redistribution phase occurs even in the absence of mechanical shearing and without appreciable effects from end-to-end annealing, as indicated by the time course of incremental changes in polymer length and MT number concentration. We also observed higher rates of MT length redistribution when the [MAP]/[tubulin] ratio was decreased. Together, these results demonstrate that MT length redistribution rates are greatly influenced by MAP content, and the data are compatible with the dynamic instability model. We also found that a peptide analogue corresponding to the second repeated sequence in the MT-binding region of MAP-2 can also markedly retard MT length redistribution kinetics, a finding that accords with the ability of this peptide to promote tubulin polymerization in the absence of MAPs and to displace MAP-2 from MTs. These results provide further evidence that MAPs can modulate MT assembly/disassembly dynamics and that peptide analogues can mimic the action of intact MAPs without the need for three contiguous repeated sequences in the MT-binding region.


A systematic review on the prevalence of preoperative and postoperative depression in lumbar fusion.
Depression and Degenerative Spine Disease (DSD) frequently co-exist. Pooled prevalence estimates of depression before and after lumbar fusion surgery has not been analyzed before. The purpose of this systematic review was to estimate the pre- and post-operative prevalence of depression in patients with DSD undergoing lumbar fusion. A literature review until April 30th 2022 was performed. All studies on DSD patients undergoing lumbar spine fusion surgery with either a history of formal diagnosis of depression or a recording of depression using a validated tool were included. Patients with other psychiatric conditions or undergoing a different form of spinal surgery were excluded. Risk of bias of the included studies was evaluated using the Newcastle-Ottawa Scale. Fifteen (15) studies with a total of 98.375 patients met the inclusion and exclusion criteria and were included in the analysis. The prevalence estimate of depression in patients before surgery was 15,35 % (95% CI: 10,56-20,86%). In the 7 studies including patients who had undergone lumbar fusion, the pooled prevalence was estimated 11,46% (95% CI: 8,11-15,30%). An increased prevalence of depression in patients undergoing lumbar spine fusion was noted. Given the correlation between depression and poor surgical outcomes, strategies should be identified to prevent and treat depression in these patients.


From the echocardiography machine to the lecture room: a simple method for transferring echocardiographic frames and loops to a personal computer.
The use of computers in scientific and educational presentations is rapidly increasing. As a digital presentation is ideal for showing moving images, the use of multimedia files, e.g., echocardiographic loops within these presentations, is common. Even though recent echocardiography machines store acquired data in a digital format, these data are often not readily accessible to be transferred to a personal computer. We present an easy and cost-efficient method for transferring frames and loops from any echocardiography machine into a personal computer using a digital video camera equipped with a standard analog input and flash memory. Still images and movies are stored in the camera to be subsequently transferred to a personal computer. In the computer, still images and movies are post-processed with graphical and video editing software. Finally, the still images and movies can be projected from the video camera or presented with specialized software such as PowerPoint. The images can also be used for Web-based publications and production of educational material or books on electronic media such as CD-ROM. The described method can also be used to transfer images from other proprietary devices and programs, as long as the devices are equipped with an analog video outlet. The transfer of frames and loops from echocardiographic machines to personal computers is often useful for publication, teaching, and educational purposes. We present an easy and cost-effective method for transferring frames and loops from any echocardiography machine into a personal computer using a digital video camera.


Shelf-life extension of Fragaria × ananassa Duch. using selenium nanoparticles synthesized from Cassia fistula Linn. leaves.
Fragaria × ananassa Duch. (Strawberry) fruit is susceptible to postharvest diseases, thus decrease in quality attributes, such as physiological and biochemical properties leads to decrease in shelf life. The objective of the present study was to check the effect of Selenium NP's and packaging conditions on the shelf life of strawberry (Fragaria × ananassa Duch) fruits. The shelf life was observed with 4 days intervals and examined for characteristics such as physiological weight loss, moisture content, percentage decay loss, peroxidase, catalase, and DPPH radical scavenging. The quality change of postharvest Fragaria × ananassa Duch. was monitored by the application of selenium nanoparticles (T1 plant extract in 10 mM salt solution, T2 plant extract in 30 mM salt solution, T3 plant extract in 40 mM salt solution, T4 distilled water; control) in different packaging materials (plastic bags, cardboard, and brown paper) at different storage conditions (6°C and 25°C). 10 mM, 20 mM, and 30 mM solution of sodium selenite salt, prepared from 1 M stock solution. Selenium nanoparticles were synthesized using Cassia fistula L. extract and sodium selenite salt solution. Polyvinyl alcohol (PVA) was used as a stabilizer. The nanoparticles were characterized through UV-visible spectroscopy and X-Ray diffractometer (XRD). It was observed that the strawberry Fragaria × ananassa Duch. Treated with T1 (CFE and 10 mM salt solution) stored in plastic packaging at ±6°C showed the best physiological parameters and hence the treatment is recommended for storage without affecting the quality of strawberry fruit up to 16 days.


Analysis of highly polar compounds in groundwater samples from ammunition waste sites. Part I-Characterization of the pollutant spectrum.
Five groundwater samples from the former ammunition production site at Elsnig, Germany, were analyzed for highly polar components by LC-NMR and LC-MS. A variety of unknown pollutants could be identified. Possibilities and limitations of the combined use of LC-NMR and LC-MS techniques for on-line identification are discussed. Further unknown components were identified through isolation by HPLC cuts and off-line NMR and MS investigations. Most of the polar compounds in the investigated samples could also be quantified.


Transforming Growth Factors α and β Are Essential for Modeling Cholangiocarcinoma Desmoplasia and Progression in a Three-Dimensional Organotypic Culture Model.
To gain insight into the cellular and molecular interactions mediating the desmoplastic reaction and aggressive malignancy of mass-forming intrahepatic cholangiocarcinoma (ICC), we modeled ICC desmoplasia and progression in vitro. A unique three-dimensional (3D) organotypic culture model was established; within a dilute collagen-type I hydrogel, a novel clonal strain of rat cancer-associated myofibroblasts (TDFSM) was co-cultured with a pure rat cholangiocarcinoma cell strain (TDECC) derived from the same ICC type as TDFSM. This 3D organotypic culture model reproduced key features of desmoplastic reaction that closely mimicked those of the in situ tumor, as well as promoted cholangiocarcinoma cell growth and progression. Our results supported a resident liver mesenchymal cell origin of the TDFSM cells, which were not neoplastically transformed. Notably, 3D co-culturing of TDECC cells with TDFSM cells provoked the formation of a dense fibrocollagenous stroma in vitro that was associated with significant increases in both proliferative TDFSM myofibroblastic cells and TDECC cholangiocarcinoma cells accumulating within the gel matrix. This dramatic desmoplastic ICC-like phenotype, which was not observed in the TDECC or TDFSM controls, was highly dependent on transforming growth factor (TGF)-β, but not promoted by TGF-α. However, TGF-α was determined to be a key factor for promoting cholangiocarcinoma cell anaplasia, hyperproliferation, and higher malignant grading in this 3D culture model of desmoplastic ICC.


Selection of early pregnancy specific proteins and development a rapid immunochromatographic test strip in cows.
The most of embryo losses occur before the day 16 after artificial insemination, but there is no low cost and easy operation that can detect pregnancy with high accuracy within three weeks post-insemination in cattle. In this study, blood samples were collected at day 18 of the estrous cycle, and days 18, 25 and 35 of pregnancy, and relative levels of interferon stimulated genes (ISGs), Toll-like receptor (TLRs), complement components, early pregnancy factor (EPF) and pregnancy-associated plasma protein A (PAPPA) proteins were analyzed through Western blot. In addition, a colloidal gold immunochromatographic test strip was developed using the selected antibody, and the test was used for early pregnancy diagnosis. The results showed that there were changes in relative levels of plasma ISGs, TLRs, complement components, EPF and PAPPA proteins during early pregnancy in cattle, and complement component 1q (C1q) could be used as an ideal marker to develop a colloidal gold immunochromatographic test strip for early pregnancy diagnosis. In addition, the accuracy of pregnancy diagnosis by this test strip was 91.67% (11/12) for pregnant cows and 80% (8/10) nonpregnant cows at day 18 after insemination. In conclusion, the changes in plasma ISGs, TLRs, complement components, EPF and PAPPA proteins may be related to the maternal systemic immune modulation during early pregnancy, and a colloidal gold immunochromatographic test strip was developed for early pregnancy diagnosis using C1q as the ideal marker in cows. However, this colloidal gold immunochromatographic test strip needs further studies to improve the accuracy.


The ubiquitin-proteasome system in breast cancer.
Ubiquitin-proteasome system (UPS) is a selective proteolytic system that is associated with the expression or function of target proteins and participates in various physiological and pathological processes of breast cancer. Inhibitors targeting the 26S proteasome in combination with other drugs have shown promising therapeutic effects in the clinical treatment of breast cancer. Moreover, several inhibitors/stimulators targeting other UPS components are also effective in preclinical studies, but have not yet been applied in the clinical treatment of breast cancer. Therefore, it is vital to comprehensively understand the functions of ubiquitination in breast cancer and to identify potential tumor promoters or tumor suppressors among UPS family members, with the aim of developing more effective and specific inhibitors/stimulators targeting specific components of this system.


Reduced sulfate plasma concentrations in the BTBR T+tf/J mouse model of autism.
Clinical studies have shown that children diagnosed with autism show abnormal sulfate chemistry, which is critical for cellular and metabolic processes. To determine if the inbred BTBR T+tf/J mouse shows autism-relevant aberrations in sulfate chemistry, the present study examined plasma sulfate concentrations in BTBR T+tf/J, inbred C57BL/6J, and outbred CD-1 mice. Results showed that the BTBR T+tf/J mouse exhibits significantly lower plasma sulfate concentrations in comparison to both C57BL/6J and CD-1 mice. These results suggest that the BTBR mouse shows autism-relevant abnormalities in sulfate chemistry and may serve additional utility in examining the role of sulfate and sulfate-dependent systems in relation to autism-relevant behavioral aberrations.


[Prenatal diagnosis of chromosomal aberrations in the second trimester of pregnancy--analysis of problems and diagnostic difficulties].
Laboratory problems and diagnostic difficulties are analysed in 1135 prenatal cytogenetic examinations of amniotic fluid cells in the Genetics Laboratory of the Mother and Child Institute. The effectiveness and the reliability of the method for the purposes of prenatal diagnosis of chromosomal aberrations were evaluated. They were comparable to those reported from other similar centres in the world.


Pneumocephalus and Sixth Nerve Palsy after Epidural Steroid Injection: Case Report and Review of the Literature.
Pneumocephalus has been described as an unintended outcome after epidural injections. However, oculomotor palsy from pneumocephalus after epidural injection is very rare. We report a case of pneumocephalus-induced sixth nerve palsies and diplopia in an 87-year-old woman after epidural steroid injection. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Pneumocephalus-induced oculomotor palsy is a rare complication after epidural injection, a commonly performed medical procedure. Knowledge of this presentation will help emergency physicians distinguish between this entity and other causes of neurologic deficits.


Identification of phenolic metabolites in human urine after the intake of a functional food made from grape extract by a high resolution LTQ-Orbitrap-MS approach.
Grape pomace (GP) is known to be a rich source of polyphenols with biological activity which may be used as functional ingredients for the development of new health-promoting products. Numerous studies have reported that bioactive compounds may act through multiple mechanisms. In order to verify the oral absorption and metabolism of grape polyphenols, we performed a prospective, randomised and cross-over acute study in 12 volunteers with two interventions: 500mL of a functional beverage enriched with 200mL of GP and 500mL of a control beverage without GP. In this work, liquid chromatography coupled with an electrospray ionization hybrid linear ion trap quadrupole-Orbitrap-mass spectrometry (LC/ESI-LTQ-Orbitrap-MS) technique has been used to accurately identify phenolics in GP and human urine. In GP, 41 phenolic compounds were identified mainly procyanidins, phenolic acids and flavonols, and in human urine over 70 metabolites of phenolic compounds including microbiota metabolites, glucuronides and sulfate derivatives were detected. Overall, high resolution mass spectrometry (HR-MS) enhances the identification of a large variety of polyphenols and their metabolites with great mass accuracies for all molecular ions.


SOCS-1 deficiency does not prevent diet-induced insulin resistance.
Obesity is associated with inflammation and increased expression of suppressor of cytokine signaling (SOCS) proteins, which inhibit cytokine and insulin signaling. Thus, reducing SOCS expression could prevent the development of obesity-induced insulin resistance. Using SOCS-1 knockout mice, we investigated the contribution of SOCS-1 in the development of insulin resistance induced by a high-fat diet (HFD). SOCS-1 knockout mice on HFD gained 70% more weight, displayed a 2.3-fold increase in epididymal fat pads mass and increased hepatic lipid content. This was accompanied by increased mRNA expression of leptin and the macrophage marker CD68 in white adipose tissue and of SREBP1c and FAS in liver. HFD also induced hyperglycemia in SOCS-1 deficient mice with impairment of glucose and insulin tolerance tests. Thus, despite the role of SOCS proteins in obesity-related insulin resistance, SOCS-1 deficiency alone is not able to prevent insulin resistance induced by a diet rich in fat.


Antidiabetic drugs and non-alcoholic fatty liver disease: A systematic review, meta-analysis and evidence map.
The efficacy of antidiabetic agents for the treatment of non-alcoholic fatty liver disease (NAFLD) remains unclear. To conduct a meta-analysis to study the efficacy of pioglitazone and three novel anti-diabetic agents: glucagon-like peptide-1 (GLP-1) agonists, sodium-glucose co-transporter-2 (SGLT2) inhibitors, and dipeptidyl-peptidase-4 (DPP4) inhibitors in treating NAFLD. Online databases were searched in May 2020 for randomized clinical trials. Results from random-effects meta-analysis are presented as weighted mean differences (WMDs) or standard mean differences (SMDs) and corresponding 95% confidence intervals (CIs). Twenty-six studies (n=946 NAFLD patients) were included. Reductions in ALT were seen with all four drugs: pioglitazone (MD -38.41, p<0.001), SGLT2 inhibitors (MD -16.17, p<0.001), GLP-1 agonists (MD -27.98, p=0.04) and DPP-4 inhibitors (MD -7.41, p<0.001). Pioglitazone (SMD -1.01; p<0.001) and GLP-1 agonists (SMD -2.53, p=0.03) also demonstrated significant improvements in liver steatosis. SGLT2 inhibitors (SMD -4.64, p=0.06) and DPP-4 (SMD -2.49, p=0.06) inhibitors trended towards reduced steatosis; however, these results were non-significant. Pioglitazone demonstrates significant improvements in transaminases and liver histology in both diabetic and non-diabetic NAFLD patients. Early evidence from diabetic NAFLD patients suggests that novel antidiabetics may lead to improvements in liver enzymes and hepatic steatosis, and this should encourage further research into possible utility of these drugs in treating NAFLD.


Skeletal height reconstruction from measurements of the skull in indigenous South Africans.
Stature reconstruction is important as it provides a forensic anthropological estimate of the height of a person in the living state; playing a vital role in the identification of individuals from their skeletal remains. Regression formulae for stature estimation have been generated for indigenous South Africans based on measurements of long bones of upper and lower extremities and the calcaneus. Since these bones are not always available for forensic analysis, it became necessary to use other bones such as the skull for stature estimation. The aim of the present study was to investigate the usefulness of certain measurements of the skull of indigenous South Africans in the estimation of adult stature. Ninety-nine complete skeletons obtained from the Raymond A. Dart Collection, School of Anatomical Sciences of the University of the Witwatersrand, were used. Total skeletal height (TSH) was calculated for each skeleton using the Fully's (anatomical) method. Furthermore, six variables were measured on each skull. TSH was regressed onto these cranial measurements in order to obtain regression formulae. The correlation coefficients obtained ranged between 0.40 and 0.54. The range of the standard errors of estimate from the current study (4.37 and 6.24) is high in comparison to that obtained for stature estimation based on intact long bones and the calcaneus. Therefore, the equations presented in this study should be used with caution in forensic cases when only the skull is available for human identification.


Fuzzy KNN for predicting membrane protein types from pseudo-amino acid composition.
Cell membranes are vitally important to the life of a cell. Although the basic structure of biological membrane is provided by the lipid bilayer, membrane proteins perform most of the specific functions. Membrane proteins are putatively classified into five different types. Identification of their types is currently an important topic in bioinformatics and proteomics. In this paper, based on the concept of representing protein samples in terms of their pseudo-amino acid composition, the fuzzy K-nearest neighbors (KNN) algorithm has been introduced to predict membrane protein types, and high success rates were observed. It is anticipated that, the current approach, which is based on a branch of fuzzy mathematics and represents a new strategy, may play an important complementary role to the existing methods in this area. The novel approach may also have notable impact on prediction of the other attributes, such as protein structural class, protein subcellular localization, and enzyme family class, among many others.


Bordetella hinzii: An Unexpected Pathogen in Native Valve Endocarditis.
Bordetella hinzii's route of transmission to human hosts and its pathogenicity remain unclear. Only a few cases have established this species as an opportunistic zoonotic disease. We introduce the first reported case of native aortic valve endocarditis presenting with fulminant aortic valve insufficiency that responded to conventional medical and surgical treatment. The patient did not have predisposing factors to this unusual infection. This case may provide a better understanding of the disease process, transmission, and pathogenicity of Bordetella hinzii.


[Effect of the addition of sorbitol to the feed of lactating cows on their performance and blood composition].
One hundred and nineteen dairy cows were given 0, 50 or 100 g sorbitol per day in the diet, in 4 trials. Three trials were conducted at the beginning of lactation, with maize silage, grass silage or grass silage and hay based diets. In the fourth trial conducted in mid-lactation, the concentrate had been enriched with fat. No sorbitol or fructose was found in blood. Sorbitol decreased free cholesterolemia (P less than 0.01), ester-cholesterolemia (P less than 0.10) and glycemia (P less than or equal to 0.05). No changes in performance were noted.


General ultrasound screening reduces the rate of first operative procedures for developmental dysplasia of the hip: a case-control study.
To assess the effectiveness of general ultrasound screening to prevent first operative procedures of the hip. We conducted a case-control study in a population in which general ultrasound screening supplementing clinical screening is recommended and offered free of charge for all children. Participation in ultrasound screening before week 7 as recommended in Germany was the exposure of interest. Case ascertainment was based on active surveillance in orthopedic hospitals. The case definition was: first operative procedure for developmental dysplasia of the hip (closed reduction, open reduction, or osteotomy) in children >9 weeks old and <5 years old and born between 1996 and 2001. Control subjects from the same birth cohorts were recruited in telephone surveys. Cases of first operative procedures for developmental dysplasia of the hip (n = 446) were compared with 1173 control subjects for ultrasound screening. Effectiveness of ultrasound screening to prevent first operative procedures for developmental dysplasia of the hip was estimated as 52% (95% CI, 32-67). Effectiveness did not vary substantially for closed and open reductions and osteotomy. General ultrasound screening reduces the rate of operative procedures for developmental dysplasia of the hip; the impact on developmental dysplasia of the hip. Treatment rates and avascular necrosis need further assessment to balance the benefit against potential overtreatment and adverse effects.


Detection and isolation of Helicobacter mustelae from stoats in New Zealand.
To determine the incidence of Helicobacter mustelae in stoats (Mustela erminea) in New Zealand. Helicobacter-like organisms and total genomic DNA were isolated from gastric tissue of stoats and identified using a combination of bacterial culture, phenotypic testing and molecular techniques. A Helicobacter-specific 16S rRNA polymerase chain reaction product was detected in 16/32 gastric tissue biopsies tested. Nine of 13 partially sequenced 16S rRNA DNA identified H. mustelae 16S DNA. Bacteria, subsequently identified as H. mustelae, were successfully cultured from the stomachs of 4/32 stoats. Other Helicobacter species were also identified by DNA sequence analysis, but were not cultured. Helicobacter mustelae is present in stoats from both the North and South Islands of New Zealand.


Biofouling inhibition by Staphylococcus aureus extracts and their potential use for paints.
For the control of biofouling, some paints based on compounds that are toxic to marine organisms have been used. There is an intensive search for biodegradable solutions that are friendly to non-target organisms. Bacteria have been shown to be a source of compounds with antifouling potential. In this work, the antifouling activity of a strain of Staphylococcus aureus was evaluated. Extracts activity against biofilm-forming bacteria and the toxicity against Artemia franciscana were evaluated. The extracts were incorporated in a hard gel and a paint matrix, and they were exposed to the sea. In both the laboratory and field, we found that the compounds produced by S. aureus have antifouling activity. The non-toxicity of the tested extracts against Artemia franciscana nauplii suggests that the extracts obtained from S. aureus could have a low ecological impact over non-target organisms. Significant differences were found in the percentage of organisms cover in hard gels with extracts and control. After 90 days, important differences were also observed between the percentage of organisms cover of the paints that contained extracts and the control. Dichloromethane extract is the most effective for the inhibition or delay of the settlement of organisms For this reason, they could be used in matrices with different applications, such as in the shipping industry, aquaculture, or any other in which biofouling is a cause of inconvenience.


Energy expenditure in the acute renal failure patient mechanically ventilated.
Twenty mechanically ventilated patients with acute renal failure were studied on 31 occasions to determine their energy expenditure (EE) during a 2 h period before a hemodialysis. Oxygen consumption and CO2 elimination were measured continuously with a mass spectrometer system. EE (1660 +/- 48 kcal day-1) was close to the total caloric intake (1682 +/- 83 kcal day-1) and represented 1.19 +/- 0.03 times the predicted resting energy expenditure (PREE) with large inter-individual variations (0.7-1.7 PREE). EE/PREE was higher when sepsis was present (1.31 +/- 0.03 versus 1.14 +/- 0.02; p less than 0.05). Glucose oxidation rate (4.35 mg kg-1 min-1) exceeded glucose intake (2.6 mg kg-1 min-1). Respiratory quotient was 1.02 +/- 0.01. Nitrogen loss was 17.3 +/- 1.7 g day-1 and nitrogen balance -11.9 +/- 1.9 g day-1. In conclusion, EE values were scattered but never exceeded 1.7 times the PREE. Sepsis increased EE. With a nutritional support covering EE, nitrogen balance remained markedly negative and a preferential utilisation of glucose and lipogenesis occurred.


The leukocidin pore: evidence for an octamer with four LukF subunits and four LukS subunits alternating around a central axis.
The staphylococcal alpha-hemolysin (alphaHL) and leukocidin (Luk) polypeptides are members of a family of related beta-barrel pore-forming toxins. Upon binding to susceptible cells, alphaHL forms water-filled homoheptameric transmembrane pores. By contrast, Luk pores are formed by two classes of subunit, F and S, rendering a heptameric structure displeasing on symmetry grounds at least. Both the subunit stoichiometry and arrangement within the Luk pore have been contentious issues. Here we use chemical and genetic approaches to show that (1) the predominant, or perhaps the only, form of the Luk pore is an octamer; (2) the subunit stoichiometry is 1:1; and (3) the subunits are arranged in an alternating fashion about a central axis of symmetry, at least when a fused LukS-LukF construct is used. The experimental approaches we have used also open up new avenues for engineering the arrangement of the subunits of beta-barrel pore-forming toxins.


MicroRNA profiling and the role of microRNA-132 in neurodegeneration using a rat model.
MicroRNAs (miRs) are endogenous small RNAs that regulate gene expression at the post-transcriptional level by mediating mRNA degradation or transcriptional inhibition. MiRs were implicated in the pathogenesis of numerous neurodegenerative diseases, including Parkinson's disease (PD). In this study we analyzed the possible role of miRs in the neurodegenerative process in a spontaneous autosomal recessive rat model for neurodegeneration developed in our laboratory. To investigate the role of miRs in the etiology of PD, we conducted miR expression profiling using microarrays. We found 20 miRs that are deregulated in affected rats and many of these are implicated in neurodegenerative disease, including PD. In this study we were particularly interested in the expression of miR-132, a miR that has been reported to be highly expressed in neurons, and to have a potential role in neurodegenerative diseases. We found a significant increase in miR-132 in affected rats by microarray and the result was confirmed by qPCR. Next we analyzed one of the known downstream targets of miR-132, nuclear receptor related 1 protein (Nurr1), which is essential in neurogenesis of midbrain dopaminergic neurons. Western blot analysis and immunohistochemistry revealed a significant decrease in Nurr1 protein expression in the mesencephalic neurons. Finally, we found a significant decrease in both serum and mesencephalon brain tissue of brain-derived neurotrophic factor (BDNF), which is known to be a direct target of Nurr1. Taken together, our findings suggest that miR-132 can regulate Nurr1 levels and might influence the development and function of midbrain dopaminergic neurons.


Paraproteinaemia in erythema elevatum diutinum.
Paraproteinaemia (IgGkappa) was observed in a 68 year-old patient with erythema elevatum diutinum. The association of this skin disease with paraproteinaemia as already reported by other authors may indicate a pathogenetic relationship.


A simple fluorescence technique to stain the plasma membrane of human neutrophils.
Three different fluorochromes were tested for their ability to label the plasma membrane proteins of neutrophils without labelling intracellular structures. A fluorescence quenching technique was used to differentiate between extra- and intracellularly localized fluorescence. Fluorescamin and fluoresceinisothiocyanate were shown to stain intracellular structures as well as the plasma membranes of the cells. Another fluorochrome, Evans Blue, is proposed since this dye was shown, by using the fluorescence quenching technique, to selectively stain the plasma membrane of viable neutrophils.


The effect of Pap smear screening on cervical cancer stage among southern Thai women.
Our study aimed to investigate the effect of Pap smear screening on stage at diagnosis of cervical cancer in a heterogeneous population of Thai women. Data was merged from the population-based cancer registry and screening registry based on unique identification numbers from 2006 to 2014. Patients being screened had lower odds to be diagnosed at late stage. After adjustment, married women had reduced risk of late stage cancer compared to single women. Muslim women had almost twice the risk of being diagnosed late stage compared to Buddhist women. The odds of being diagnosed at late stage decreased with increased number of screening. The probability of being diagnosed at late stage increased rapidly among females aged 40 to 55 years. Pap smear screening is a protective factor in diagnosis of late stage cervical cancer. Patients were more likely to be diagnosed at early stage with more frequent screening. For future screening programs, it will be beneficial to shorten screening intervals and take more concern for vulnerable population: women aged between 40 and 55 years, and women who are single or Muslim.


Assessment of myocardial systolic wall thickening using nuclear magnetic resonance imaging.
A quantitative nuclear magnetic resonance (NMR) imaging method of evaluating regional left ventricular function was compared with histochemical evidence of infarction in dogs and functional measurements in patients. Short-axis images of the heart were obtained at end-diastole and at 100 ms intervals thereafter. Regional diastolic left ventricular wall thickness and maximal percent systolic wall thickening were measured at the level of the papillary muscles in each of six segments. In six normal dogs, the mean end-diastolic wall thickness was 9 +/- 1.6 mm, and the mean maximal percent thickening was 61 +/- 11%. In eight dogs with a 4 day old infarct, maximal percent thickening was 5 +/- 8% (p less than 0.001) in the infarcted segments. In 10 normal human volunteers, the mean end-diastolic wall thickness was 10.1 +/- 1 mm, and the mean maximal percent systolic wall thickening was 60 +/- 18%. Reduced maximal percent systolic wall thickening was defined as a value greater than or equal to 2 SD below the mean value obtained in normal volunteers. Seven patients with regional wall motion abnormalities were independently assessed by NMR imaging and biplane ventriculography. With a sensitivity of 94% and a specificity of 80%, NMR imaging demonstrated reduced maximal percent systolic wall thickening in the same segments identified as akinetic or dyskinetic by biplane ventriculography. Thus, abnormalities of regional systolic wall thickening are accurately identified with this quantitative imaging technique.


Solution interactions between the uranyl cation [UO2(2+)] and histidine, N-acetyl-histidine, tyrosine, and N-acetyl-tyrosine.
Complexes of the uranyl cation [UO(2)(2+)] with histidine (His), N-acetyl-histidine (NAH), tyrosine (Tyr), and N-acetyl-tyrosine (NAT) were studied by UV-visible and NMR spectroscopy, and by potentiometric titration. Protonation constants for each ligand are reported, as are cumulative formation constants for uranyl-amino acid complexes. Coupling constant data (J(CH)) for uranyl-histidine complexes indicate that inner-sphere solution interactions between histidine and uranyl cation are solely at the carboxylate site. At 25 degrees C the major uranyl-histidine complex has a cumulative formation constant of logbeta(110)=8.53, and a proposed formula of [UO(2)HisH(2)(OH)(2)](+); the stepwise formation constant, logK(UL), is estimated to be 5.6 ( approximately 8.53-(-6.1)-(-6.1)-15.15). Outer-sphere interactions, H-bonding or electrostatic interactions, are proposed as contributing a significant portion of the stability to the ternary uranyl-hydroxo-amino acid complexes. The temperature dependent protonation constants of histidine and formation constants between uranyl cation and histidine are reported from 10 to 35 degrees C; at 25 degrees C, DeltaG=-43.3 kJ/mol.


Regional opening strategies with commuter testing and containment of new SARS-CoV-2 variants in Germany.
Despite the vaccination process in Germany, a large share of the population is still susceptible to SARS-CoV-2. In addition, we face the spread of novel variants. Until we overcome the pandemic, reasonable mitigation and opening strategies are crucial to balance public health and economic interests. We model the spread of SARS-CoV-2 over the German counties by a graph-SIR-type, metapopulation model with particular focus on commuter testing. We account for political interventions by varying contact reduction values in private and public locations such as homes, schools, workplaces, and other. We consider different levels of lockdown strictness, commuter testing strategies, or the delay of intervention implementation. We conduct numerical simulations to assess the effectiveness of the different intervention strategies after one month. The virus dynamics in the regions (German counties) are initialized randomly with incidences between 75 and 150 weekly new cases per 100,000 inhabitants (red zones) or below (green zones) and consider 25 different initial scenarios of randomly distributed red zones (between 2 and 20% of all counties). To account for uncertainty, we consider an ensemble set of 500 Monte Carlo runs for each scenario. We find that the strength of the lockdown in regions with out of control virus dynamics is most important to avoid the spread into neighboring regions. With very strict lockdowns in red zones, commuter testing rates of twice a week can substantially contribute to the safety of adjacent regions. In contrast, the negative effect of less strict interventions can be overcome by high commuter testing rates. A further key contributor is the potential delay of the intervention implementation. In order to keep the spread of the virus under control, strict regional lockdowns with minimum delay and commuter testing of at least twice a week are advisable. If less strict interventions are in favor, substantially increased testing rates are needed to avoid overall higher infection dynamics. Our results indicate that local containment of outbreaks and maintenance of low overall incidence is possible even in densely populated and highly connected regions such as Germany or Western Europe. While we demonstrate this on data from Germany, similar patterns of mobility likely exist in many countries and our results are, hence, generalizable to a certain extent.


Methylation of cytochrome p450 2E1 promoter induced by low dosage of isoniazid.
To find new diagnostic markers to monitor isoniazid-induced liver injury. SD rats were treated with low dosage of isoniazid and the light microscopic findings of livers were collected. The methylation status of cytochrome p450 2E1 promoter was determined. Cell edema and spotty necrosis on liver cells appeared in the experimental group and promoter methylation of cytochrome p450 2E1 was detected. Low-dosage isoniazid can induce liver injury.


Calcified constrictive pericarditis resulting in tamponade in a patient with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiorgan involvement, including heart. Pericarditis-the most common cardiac manifestation-occurs in up to 50% of cases, resulting in positive treatment outcomes. Rarely, it evolves to hazardous complications. A 50-year-old woman with SLE in clinical remission, receiving hydroxychloroquine 400 mg/day, presented to us with severe chest pain and low-grade fever. Physical examination revealed a friction rub and decreased breath sounds at the right lung base. Laboratory evaluation demonstrated leukopenia, thrombocytopenia, low C4 levels, and high acute phase reactants. Chest X-ray exhibited cardiomegaly, calcified pericardium, and right pleural effusion, confirmed by CT scan. PPD skin test and IGRA were both negative. Pericardial fluid, blood, and urine cultures for bacteria and fungi, as well as Gram and Ziehl-Neelsen stains were negative. Serological tests for viruses were also negative. The patient was diagnosed with calcified constrictive pericarditis (CP) due to SLE. She was treated with cyclophosphamide and methylprednisolone pulses, without improvement. Her clinical condition deteriorated, developing signs and symptoms compatible with cardiac tamponade (TMP), which was confirmed by Doppler echocardiography. The patient underwent pericardiectomy. A dramatic response was noted and she was discharged with prednisone 50 mg/day and azathioprine 100 mg/day. Thus, we review and discuss the relevant literature of SLE cases with CP or TMP. When an SLE patient presents with CP, infectious causes should be excluded first. To the best of our knowledge, this is the only case of SLE and calcified CP leading to TMP, hence physicians should be aware of this complication.


Lipidome remodeling in aging normal and genetically obese Drosophila males.
Lipid homeostasis is essential for insects to maintain phospholipid (PL)-based membrane integrity and to provide on-demand energy supply throughout life. Triacylglycerol (TAG) is the major lipid class used for energy production and is stored in lipid droplets, the universal cellular fat storage organelles. Accumulation and mobilization of TAG are strictly regulated since excessive accumulation of TAG leads to obesity and has been correlated with adverse effects on health- and lifespan across phyla. Little is known, however, about when during adult life and why excessive storage lipid accumulation restricts lifespan. We here used genetically obese Drosophila mutant males, which were all shown to be short-lived compared to control males and applied single fly mass spectrometry-based lipidomics to profile TAG, diacylglycerol and major membrane lipid signatures throughout adult fly life from eclosion to death. Our comparative approach revealed distinct phases of lipidome remodeling throughout aging. Quantitative and qualitative compositional changes of TAG and PL species, which are characterized by the length and saturation of their constituent fatty acids, were pronounced during young adult life. In contrast, lipid signatures of adult and senescent flies were remarkably stable. Genetically obese flies displayed both quantitative and qualitative changes in TAG species composition, while PL signatures were almost unaltered compared to normal flies at all ages. Collectively, this suggests a tight control of membrane composition throughout lifetime largely uncoupled from storage lipid metabolism. Finally, we present first evidence for a characteristic lipid signature of moribund flies, likely generated by a rapid and selective storage lipid depletion close to death. Of note, the analytical power to monitor lipid species profiles combined with high sensitivity of this single fly lipidomics approach is universally applicable to address developmental or behavioral lipid signature modulations of importance for insect life.


Human papillomaviruses: targeting differentiating epithelial cells for malignant transformation.
Human papillomavirus (HPV) infections play a crucial role in the pathogenesis of cervical neoplasia. Insights into the mechanisms by which HPV infection can, in a small numbers of cases, result in malignancy, comes from the observation that three proteins encoded by high-risk genital HPVs, E6, E7 and to a lesser extent E5, target factors that control the cell cycle and proliferation. These interactions result in abrogation of cell cycle control, chromosomal alterations, telomerase activation, and eventual cell immortalization. In this review, we discuss the functions of E6, E7, and E5 proteins that are most relevant to the malignant progression of HPV-transformed cells.


Establishment and validation of preclinical models of SMARCA4-inactivated and ARID1A/ARID1B co-inactivated dedifferentiated endometrial carcinoma.
Dedifferentiated endometrial cancer (DDEC) is an uncommon and clinically highly aggressive subtype of endometrial cancer characterized by genomic inactivation of SWItch/Sucrose Non-Fermentable (SWI/SNF) complex protein. It responds poorly to conventional systemic treatment and its rapidly progressive clinical course limits the therapeutic windows to trial additional lines of therapies. This underscores a pressing need for biologically accurate preclinical tumor models to accelerate therapeutic development. DDEC tumor from surgical samples were implanted into immunocompromised mice for patient-derived xenograft (PDX) and cell line development. The histologic, immunophenotypic, genetic and epigenetic features of the patient tumors and the established PDX models were characterized. The SMARCA4-deficienct DDEC model was evaluated for its sensitivity toward a KDM6A/B inhibitor (GSK-J4) that was previously reported to be effective therapy for other SMARCA4-deficient cancer types. All three DDEC models exhibited rapid growth in vitro and in vivo, with two PDX models showing spontaneous development of metastases in vivo. The PDX tumors maintained the same undifferentiated histology and immunophenotype, and exhibited identical genomic and methylation profiles as seen in the respective parental tumors, including a mismatch repair (MMR)-deficient DDEC with genomic inactivation of SMARCA4, and two MMR-deficient DDECs with genomic inactivation of both ARID1A and ARID1B. Although the SMARCA4-deficient cell line showed low micromolecular sensitivity to GSK-J4, no significant tumor growth inhibition was observed in the corresponding PDX model. These established patient tumor-derived models accurately depict DDEC and represent valuable preclinical tools to gain therapeutic insights into this aggressive tumor type.


Incidence of gestational trophoblastic disease in Stockholm County, 1975-1988.
An epidemiological study with the aim of establishing the incidence of hydatidiform mole, persistent trophoblastic disease and choriocarcinoma in Stockholm County was performed. Based on the regional cancer registry and hospital registers, the incidence for 1975-1988 was calculated for the number of deliveries as well as the total number of pregnancies. Of the molar pregnancies, 6% were treated with chemotherapy because of invasive mole or choriocarcinoma. Non-molar choriocarcinoma occurred in 1/33,717 deliveries. Difficulties in assessing the incidence of gestational trophoblastic disease are discussed.


One-year outcomes of coronary artery bypass graft surgery versus percutaneous coronary intervention with multiple stenting for multisystem disease: a meta-analysis of individual patient data from randomized clinical trials.
We aimed to provide a quantitative analysis of the 1-year clinical outcomes of patients with multisystem coronary artery disease who were included in recent randomized trials of percutaneous coronary intervention with multiple stenting versus coronary artery bypass graft surgery. An individual patient database was composed of 4 trials (Arterial Revascularization Therapies Study, Stent or Surgery Trial, Argentine Randomized Trial of Percutaneous Transluminal Coronary Angioplasty Versus Coronary Artery Bypass Surgery in Multivessel Disease 2, and Medicine, Angioplasty, or Surgery Study 2) that compared percutaneous coronary intervention with multiple stenting (N = 1518) versus coronary artery bypass graft surgery (N = 1533). The primary clinical end point of this study was the combined incidence of death, myocardial infarction, and stroke at 1 year after randomization. Secondary combined end points included the incidence of repeat revascularization at 1 year. All analyses were based on the intention-to-treat principle. After 1 year of follow-up, 8.7% of patients randomized to percutaneous coronary intervention with multiple stenting versus 9.1% of patients randomized to coronary artery bypass graft surgery reached the primary clinical end point (hazard ratio 0.95 and 95% confidence interval 0.74-1.2). Repeat revascularization procedures occurred more frequently in patients allocated to percutaneous coronary intervention with multiple stenting compared with coronary artery bypass graft surgery (18% vs 4.4%; hazard ratio 4.4 and 95% confidence interval 3.3-5.9). The percentage of patients who were free from angina was slightly lower after percutaneous coronary intervention with multiple stenting than after coronary artery bypass graft surgery (77% vs 82%; P = .002). One year after the initial procedure, percutaneous coronary intervention with multiple stenting and coronary artery bypass graft surgery provided a similar degree of protection against death, myocardial infarction, or stroke for patients with multisystem disease. Repeat revascularization procedures remain high after percutaneous coronary intervention, but the difference with coronary artery bypass graft surgery has narrowed in the era of stenting.


Older adults: should the paradigm shift from standard therapy?
For older adults (ie, those age 60 and above) with acute myelogenous leukemia, patient and clinician have three choices: standard therapy, ie, a "3+7" regimen or low-dose ara-C, investigational therapy, or palliative care. Investigational treatments sponsored by pharmaceutical companies tend to exclude the 10-20% of older patients who have a poor performance status (Zubrod >2), an increased bilirubin, or creatinine (>1.9 mg/ml) and who are thereby unlikely to do well with standard therapy. However, even excluding such patients, standard treatment offers little obvious benefit for most older patients. Nonetheless, these older patients are not uniform and can be stratified to receive investigational therapy, which is mandatory for most, or standard therapy, which is not inappropriate for some.


Recovery of transforming EBV from non-producer cells after superinfection with non-transforming P3HR-1 EBV.
Cells of the Raji and NC37 lines can be induced by chemical inducers, such as BrdUrd and IdUrd, or the tumor-promoter TPA to EA-expression only, but do not reveal any VCA synthesis. After superinfection by nontransforming P3HR-1 EBV, however, a varying percentage of the cell population shows VCA synthesis and releases infectious viral particles. The recovered virus differs biologically from P3HR-1 EBV since it transforms human umbilical cord blood lymphocytes into EBNA-positive lymphoblastoid cell lines. Cells of these established lines are susceptible to renewed infection by P3HR-1 EBV which results in EA induction and VCA synthesis. Only cells of one line, NC37-R1, spontaneously produce VCA and EBV particles, which reveal transforming properties and do not induce EA upon superinfection of Raji cells. Infection of P3HR-1 EBV-converted BJA-B cells also leads to EA and VCA induction and the release of viral particles. In contrast to particles recovered from Raji and NC37 cells, no transforming activity was detectable in these virus preparations. According to these data, we propose that viral genomes persisting within Raji and NC37 cells are defective and become complemented by the superinfecting P3HR-1 virus.


The suitability of a DRG casemix system in the Maltese hospital setting.
The healthcare system in Malta is financed through global budgets and healthcare is provided free at the point of use. This paper is a first attempt to examine the feasibility of introducing a Diagnosis Related Groups casemix system for Malta, not necessarily for payment and funding purposes, but as a tool to help describe, manage and measure resource use. This is particularly challenging in view of the constraints and characteristics of a small state country. The study evaluates the applicability of the MS-DRG (Version 27.0) Grouper to describe acute hospital activity on the island. The classification of 151,615 admissions between 2009-2011 resulted in 636 DRG categories. Around half of these DRGs accounted for 99% of the total activity at the hospital, while 296 DRG categories had fewer than 15 cases over the period. Patient length of stay is used to explain resource use and the Coefficient of Multiple Determination obtained was of 0.19 (improving to 0.25 when a number of trimming algorithms were applied). A good proportion of the resulting DRGs had a Coefficient of Variation, which indicates a low degree of variability within the obtained DRG groups. This presents good evidence to support the introduction of a DRG system in Malta particularly in view of the recent drive towards more public-private partnerships and legislation on cross-border patient treatment.


Recombinant attenuated Vibrio cholerae strains used as live oral vaccines.
Although great strides have been made in the development of recombinant attenuated Vibrio cholerae vaccine strains, the task has not been as simple as once imagined. The initial vaccine candidates proved to be unexpectedly reactogenic but further derivatives, such as CVD103-HgR, are well-tolerated, immunogenic and protective after a single dose. In addition, this strain carries a selectable marker to distinguish it from wild strains and has been evaluated in a practical, lyophilized formulation (Levine et al., 1988b). While CVD103-HgR is being further evaluated in expanded trials, we are also investigating a new secretogenic factor which could possibly explain the diarrhoea seen with the earlier vaccine strains. Hopefully, these studies will achieve the long-sought goal of a safe and effective vaccine for the prevention of cholera.


The acquisition of automatic response biases through categorization.
Participants categorized left- and right-pointing line drawings presented together with pictures, whose pointing direction (to the left or right) was ambiguous (spatially ambiguous pictures; Experiments 1 and 2) or that pointed neither to the left nor to the right (spatially neutral pictures; Experiment 3). Subsequently, the spatially ambiguous and neutral pictures were used in a Simon task, wherein participants made left and right keypresses on the basis of the color of the pictures, while ignoring the object that they depicted. In all three experiments, performance was facilitated when the response required by the color matched the pointing direction of the line drawings with which the picture had been previously paired. Performance was impeded when the response required by the color did not match the pointing direction of the line drawings with which the picture had been previously paired. Thus, responses indirectly associated with pictures by category membership were automatically triggered even when the responses were inappropriate.


Monoclonal antibodies to alpha 2u-globulin and immunocytofluorometric analysis of alpha 2u-globulin-synthesizing hepatocytes during androgenic induction and aging.
Stable hybridomas generated by fusion of spleen cells from hyperimmunized mice and mouse myeloma cells were cloned to prepare monoclonal antibodies to alpha 2u-globulin, an androgen-dependent urinary protein of hepatic origin. One of these monoclonal antibodies was used as a probe for immunocytofluorometric analysis of alpha 2u-globulin producing hepatocytes during androgenic induction and aging through fluorescence-activated cell sorting (FACS). FACS patterns of hepatocytes from mature male rats that produce high levels of alpha 2u-globulin showed tow distinct peaks, arbitrarily designated as peak I (weakly fluorescent) and peak II (brightly fluorescent). In the mature male rat, peak II represented about 40% of the total hepatocytes, and the fluorescence intensity of this subpopulation decreased in direct correspondence with the gradual decline of alpha 2u-globulin synthesis during aging. Similarly the androgenic induction of this protein in ovariectomized female rats was associated with an increase in the fluorescence intensity of the hepatocyte subpopulation under peak II rather than an increase in the relative number of these cells. From these results we conclude that the androgen-dependent synthesis of alpha 2u-globulin and its alteration during aging are confined to a specific subpopulation of hepatocytes within the liver.


An in vivo toxicity assessment of piezoelectric sodium potassium niobate [NaxK1-xNbO3 (x = 0.2-0.8)] nanoparticulates towards bone tissue engineering approach.
One of the recent challenges in the design/development of prosthetic orthopedic implants is to address the concern of local/systemic toxicity of debris particles, released due to wear or degradation. Such debris particles often lead to inflammation at the implanted site or aseptic loosening of the prosthesis which results in failure of the implant during long run. Several in vitro studies demonstrated the potentiality of piezoelectric sodium potassium niobate [NaxK1-xNbO3 (x = 0.2, 0.5, 0.8), NKN] as an emerging next-generation polarizable orthopedic implant. In this perspective, we performed an in vivo study to examine the local and systemic toxicity of NKN nanoparticulates, as a first report. In the present study, male Wistar rats were intra-articularly injected to the knee joint with 100 μl of NKN nanoparticulates (25 mg/ml in normal saline). After 7 days of exposure, the histopathological analyses demonstrate the absence of any inflammation or dissemination of nanoparticulates in vital organs such as heart, liver, kidney and spleen. The anti-inflammatory cytokines (IL-4 and IL-10) profile analyses suggest the increased anti-inflammatory response in the treated rats as compared to non-injected (control) rats, preferably for the sodium and potassium rich NKN i.e., Na0.8K0.2NbO3 and Na0.2K0.8NbO3. The biochemical analyses revealed no pathological changes in the liver and kidney of particulate treated rats. The present study is the first proof to confirm the non-toxic nature of NKN nanoparticulates which provides a step forward towards the development of prosthetic orthopedic implants using biocompatible piezoelectric NKN ceramics.


Microarray Technology and Its Applications for Detecting Plasma microRNA Biomarkers in Digestive Tract Cancers.
Many cancers are known to be regulated by microRNAs (miRNAs), and the relationships between tissue miRNA expression levels and the amounts of miRNA circulating in the plasma (or plasma miRNA) have been examined in many types of cancers, including digestive tract cancers. The role of plasma miRNAs has yet to be elucidated in detail; therefore a comprehensive analysis of plasma miRNAs using microarrays should assist in establishing the utility of liquid biopsy or companion diagnosis. We here described the 3D-Gene(®) miRNA microarray (TORAY) currently used in our laboratory and introduced a trial application in digestive tract cancer diagnosis.


Blink reflex in end-stage-renal disease patients undergoing hemodialysis.
This study analyses the blink reflex in 20 adult male patients with terminal chronic renal failure undergoing hemodialysis. Abnormalities were found in ten patients (50%), eight of them with conduction studies showing axonal peripheral neuropathy. Dialysis time was longer for patients with blink reflex alterations (median 55.1 months) than for patients with normal blink reflex (median 36.3 months). Different types of early R1 and late R2 component abnormalities were recorded. The late response abnormalities may indicate subclinical functional or anatomical impairment of the low brainstem reticular formation in patients with chronic renal failure.


Retinal carotenoids can attenuate formation of A2E in the retinal pigment epithelium.
A2E, an important constituent of lipofuscin in human retinal pigment epithelium (RPE), is thought to mediate light-induced oxidative damage associated with aging and other ocular disorders. Ocular carotenoids in overlying retinal tissues were measured by HPLC and mass spectrometry and were correlated with levels of RPE A2E. We observed a statistically significant increase in total A2E levels in human RPE/choroid with age, and A2E levels in macular regions were approximately 1/3 lower than in peripheral retinal regions of the same size. There was a statistically significant inverse correlation between peripheral retina carotenoids and peripheral RPE/choroid A2E. Prospective carotenoid supplementation studies in Japanese quail demonstrated nearly complete inhibition of A2E formation and oxidation. These findings support current recommendations to increase dietary intake of xanthophyll carotenoids in individuals at risk for macular degeneration and highlight a new potential mechanism for their protective effects-inhibition of A2E formation and oxidation in the eye.


Dynamic palmar dislocation of the ulnar head at the distal radioulnar joint (DRUJ) after radius shaft malunion.
Palmar instability of the distal radioulnar joint (DRUJ) is a rare condition, which is, in contrast to the dorsal dislocation, scarcely represented in the literature. This palmar instability can result from a dorsally angulated malunion of the radial shaft after forearm fracture in childhood. Treating such a condition is controversial in the literature and was described in small case series. This study represents the largest case series in the literature that dealt with this condition, alongside a review of the key papers in the English literature. This is a retrospective case series. Ten patients were operated between 2007 and 2014. Six patients could be followed up clinically and radiologically after radius corrective osteotomy at the site of malunion with a mean time of 5.6 years. Patient history revealed a conservatively treated forearm fracture in childhood, a symptom-free period of several years [mean of 21.5 (min-max: 9.4-26.5) years] and a minor trauma as a trigger for clinical symptoms. All patients had clinically a DRUJ instability with palmar luxation of the ulnar head at supination. A diagnostic key feature is a radiograph of the whole forearm, revealing malunion of the radius at shaft level. Retrospective patient history, diagnostic imaging, operative technique and clinical results (DASH, modified Mayo Wrist Score, pain, grip strength, range of motion) were analyzed. Four patients were lost to follow-up. In all patients, a radius corrective osteotomy could stabilize the DRUJ. In one patient, the osteosynthesis was revised due to metal failure after one month. In all the six patients, bony union of the osteotomy was achieved. In another patient, an additional ulnar shortening osteotomy was done one year later due to a positive ulnar variance. Postoperative range of motion of the wrist had an average of 136° in extension/flexion and 149° in pronation/supination, and grip strength was 89% of the opposite side. With an average of 12.5 points at the DASH score and 82 at the modified Mayo Wrist Score, patients rated their hand function as good. In this patient cohort, a simple corrective osteotomy of the radial shaft at the malunion site was adequate to treat the dynamic palmar instability of DRUG. A soft tissue procedure was not required. Forearm radiographs are the mainstay of diagnostic tools.


Variability in PET image quality and quantification measured with a permanently filled 68Ge-phantom: a multi-center study.
This study evaluated, as a snapshot, the variability in quantification and image quality (IQ) of the clinically utilized PET [18F]FDG whole-body protocols in Finland using a NEMA/IEC IQ phantom permanently filled with 68Ge. The phantom was imaged on 14 PET-CT scanners, including a variety of models from two major vendors. The variability of the recovery coefficients (RCmax, RCmean and RCpeak) of the hot spheres as well as percent background variability (PBV), coefficient of variation of the background (COVBG) and accuracy of corrections (AOC) were studied using images from clinical and standardized protocols with 20 repeated measurements. The ranges of the RCs were also compared to the limits of the EARL 18F standards 2 accreditation (EARL2). The impact of image noise on these parameters was studied using averaged images (AVIs). The largest variability in RC values of the routine protocols was found for the RCmax with a range of 68% and with 10% intra-scanner variability, decreasing to 36% when excluding protocols with suspected cross-calibration failure or without point-spread-function (PSF) correction. The RC ranges of individual hot spheres in routine or standardized protocols or AVIs fulfilled the EARL2 ranges with two minor exceptions, but fulfilling the exact EARL2 limits for all hot spheres was variable. RCpeak was less dependent on averaging and reconstruction parameters than RCmax and RCmean. The PBV, COVBG and AOC varied between 2.3-11.8%, 9.6-17.8% and 4.8-32.0%, respectively, for the routine protocols. The RC ranges, PBV and COVBG were decreased when using AVIs. With AOC, when excluding routine protocols without PSF correction, the maximum value dropped to 15.5%. The maximum variability of the RC values for the [18F]FDG whole-body protocols was about 60%. The RC ranges of properly cross-calibrated scanners with PSF correction fitted to the EARL2 RC ranges for individual sphere sizes, but fulfilling the exact RC limits would have needed further optimization. RCpeak was the most robust RC measure. Besides COVBG, also RCs and PVB were sensitive to image noise.


Suspected Malignant Hyperthermia and the Application of a Multidisciplinary Response.
Malignant hyperthermia (MH) is a critical and potentially life-threatening emergency associated with inhaled anesthetic and depolarizing neuromuscular blocker administration. This is a single center's response to MH. When signs of MH are observed, a page for "anesthesia STAT-MH crisis" is called, triggering a multidisciplinary response, including the deployment of a Malignant Hyperthermia Cart. The MH cart and the delegation of duties allows nurses, physicians and pharmacists to quickly understand their role in the stabilization, transition and recovery of a suspected MH patient. This case highlights the importance of multi-disciplinary involvement in these rare, but potentially fatal, cases.


Dopamine-mediated striatal activity and function is enhanced in GlyRα2 knockout animals.
The glycine receptor alpha 2 (GlyRα2) is a ligand-gated ion channel which upon activation induces a chloride conductance. Here, we investigated the role of GlyRα2 in dopamine-stimulated striatal cell activity and behavior. We show that depletion of GlyRα2 enhances dopamine-induced increases in the activity of putative dopamine D1 receptor-expressing striatal projection neurons, but does not alter midbrain dopamine neuron activity. We next show that the locomotor response to d-amphetamine is enhanced in GlyRα2 knockout animals, and that this increase correlates with c-fos expression in the dorsal striatum. 3-D modeling revealed an increase in the neuronal ensemble size in the striatum in response to D-amphetamine in GlyRα2 KO mice. Finally, we show enhanced appetitive conditioning in GlyRα2 KO animals that is likely due to increased motivation, but not changes in associative learning or hedonic response. Taken together, we show that GlyRα2 is an important regulator of dopamine-stimulated striatal activity and function.


Activation of innate immunity by lysozyme fibrils is critically dependent on cross-β sheet structure.
Inflammation occurs in many amyloidoses, but its underlying mechanisms remain enigmatic. Here we show that amyloid fibrils of human lysozyme, which are associated with severe systemic amyloidoses, induce the secretion of pro-inflammatory cytokines through activation of the NLRP3 (NLR, pyrin domain containing 3) inflammasome and the Toll-like receptor 2, two innate immune receptors that may be involved in immune responses associated to amyloidoses. More importantly, our data clearly suggest that the induction of inflammatory responses by amyloid fibrils is linked to their intrinsic structure, because the monomeric form and a non-fibrillar type of lysozyme aggregates are both unable to trigger cytokine secretion. These lysozyme species lack the so-called cross-β structure, a characteristic structural motif common to all amyloid fibrils irrespective of their origin. Since fibrils of other bacterial and endogenous proteins have been shown to trigger immunological responses, our observations suggest that the cross-β structural signature might be recognized as a generic danger signal by the immune system.


Beta cell imaging - a key tool in optimized diabetes prevention and treatment.
The prevalence of diabetes is 382 million worldwide, and is expected to rise to 592 million in 2035 (http://www.idf.org/diabetesatlas); 2.5-15% of national annual healthcare budgets are related to diabetes care, potentially increasing to 40% in high-prevalence countries. Beta cell dysfunction and death are central events in diabetes pathogenesis, but the natural history of beta cell loss remains unknown. Clinical imaging of beta cells will play a pivotal role in developing strategies for optimized diabetes prevention and treatment.


Analysis of antibodies that recognize the B-epitopes formed on protein antigens by glutaraldehyde treatment: an efficient method of their neutralization.
Immunochemical analysis of antigenic determinants (AD) formed on protein macromolecules by glutaraldehyde (GA) treatment with subsequent block of free aldehyde groups with glycine was performed. The structure of the epitopes was analyzed using BSA and ovalbumin (Ova) treated with GA with subsequent block of the active groups with glycine and other amino acids. The products of reaction of GA with Gly, Lys, Pro, and His were used as hapten-like antigens that mimic GA antigenic determinants (GA-AD). Indirect and competitive enzyme-linked immunoassay and immunoaffinity chromatography revealed two regions of epitope density in the structure of the GA determinant. It is shown that the product of GA reaction with Gly efficiently blocks the antibodies raised against GA-treated proteins. Based on this finding, a method of assay of the peptide-specific antibodies of the immune complexes with the peptide--protein conjugate in the presence of antibodies to the linking agents is suggested.


Biotechnological interventions of in vitro propagation and production of valuable secondary metabolites in Stevia rebaudiana.
Plant cell and tissue culture makes provision of a sustainable and nature-friendly strategy for the production of secondary metabolites, and modern progress in gene editing and genome engineering provides novel possibilities to improve both the qualitative and quantitative aspects of such phytochemicals. The ever-expanding quest for plant-based medicine to treat diabetes facilitates large-scale cultivation of Stevia rebaudiana to enhance the yield of its much-coveted low-calorie sweetener glycosides. The potential to process stevia as a "natural" product should enhance the acceptance of steviosides as a natural calorie-free sweetener especially suitable for use in diabetic and weight control drinks and foods. Besides sweetener agents, S. rebaudiana is a potent source of many antioxidant compounds and is used to cure immunodeficiencies, neurologic disorders, inflammation, diabetes mellitus, Parkinson's disease, and Alzheimer's disease. This comprehensive review presents the research outcomes of the many biotechnological interventions implicated to upscale the yield of steviol glycosides and its derivatives in in vitro cell, callus, tissue, and organ cultures with notes on the use of bioreactor and genetic engineering in relation to the production of these valuable compounds in S. rebaudiana. KEY POINTS: • Critical and updated assessment on sustainable production of steviol glycosides from Stevia rebaudiana. • In vitro propagation of S. rebaudiana and elicitation of steviol glycosides production. • Genetic fidelity and diversity assessment of S. rebaudiana using molecular markers.