Changes in patient perception and behavior following Mohs micrographic surgery.
Mohs micrographic surgery (MMS) is used for the removal of difficult or recurrent skin cancer. Little is known about the behavioral changes of patients who have undergone this procedure. This study was conducted to document patients' long-term psychological and behavioral changes following MMS. A survey was mailed to a sample of 260 persons who underwent the Mohs procedure in 1997. It included questions on sunscreen use, level of anxiety about cancer, patient confidence in MMS, and changes in high-risk habits. The study included 214 patients who responded to our mailed questionnaire. Trends showed an increase in some but not all preventative measures taken to avoid skin cancer recurrence post-MMS. Other healthy lifestyle changes, such as decreased cigarette smoking, were not noted. Mohs micrographic surgery has an impact on some aspects of patients' health-related behavior, especially skin cancer prevention. Other aspects which are not affected may be targets for extra patient education.


A metabolic and functional overview of brain aging linked to neurological disorders.
Close correlations have recently been shown among the late onset complications encountered in diabetes and aging linked to neurobiological disorders. Aging in females and males is considered as the end of natural protection against age related diseases like osteoporosis, coronary heart disease, diabetes, Alzheimer's disease and Parkinson's disease, dementia, cognitive dysfunction and hypernatremia. Beside the sex hormones other hormonal changes are also known to occur during aging and many common problems encountered in the aging process can be related to neuroendocrine phenomena. Diabetes mellitus is associated with moderate cognitive deficits and neurophysiologic and structural changes in the brain, a condition that may be referred to as diabetes encephalopathy; diabetes increases the risk of dementia especially in the elderly. The current view is that the diabetic brain features many symptoms that are best described as accelerated brain aging. This review presents and compares biochemical, physiological, electrophysiological, molecular, and pathological data from neuronal tissue of aging and hormone treated control and diabetic animals to arrive at the similarities among the two naturally occuring physiological conditions. Animal models can make a substantial contribution to understanding of the pathogenesis, which share many features with mechanism underlying brain aging. By studying the pathogenesis, targets for pharmacology can be identified, finally leading to delay or prevention of these complications. Antiaging strategies using hormone therapy, chemical and herbal compounds were carried out for reversal of aging effects. Neuronal markers have been presented in this review and similarities in changes were seen among the aging, diabetes and hormone treated (estrogen, DHEA and insulin) brains from these animals. A close correlation was observed in parameters like oxidative stress, enzyme changes, and pathological changes like lipofuscin accumulation in aging and diabetic brain.


Impact of lipophilic efficiency on compound quality.
Lipophilic efficiency indices such as LLE and LELP were suggested to support balanced optimization of potency and ADMET profile. Here we investigated the performance of LLE and LELP on multiple data sets representing different stages of drug discovery including fragment and HTS hits and leads, development candidates, phase II compounds, and launched drugs. Analyzing their impact on ADME and safety properties and binding thermodynamics, we found that both LLE and LELP help identifying better quality compounds. LLE is sensible for the development stages but does not prefer fragment-type hits, while LELP has an advantage for this class of compounds and discriminates preferred starting points effectively. Both LLE and LELP have significant impact on ADME and safety profiles; however, LELP outperforms LLE in risk assessment at least on the present data set. On the basis of the results reported here, monitoring lipophilic efficiency metrics could contribute significantly to compound quality and might improve the output of medicinal chemistry programs.


Diabetes: a major risk factor in trauma and orthopaedic surgery.
Diabetes mellitus is a growing epidemic and places a great burden on healthcare services in the UK. Trauma and orthopaedic surgeons find themselves dealing with patients with diabetes on an increasingly regular basis. Any level of surgical trauma can lead to a physiological stress response involving the hypothalamic-pituitary-adrenal axis. The resultant hormone releases can have negative effects on glucose homeostasis. General risks of operating on patients with diabetes include endothelial dysfunction, postoperative sepsis, impaired wound healing and cerebral ischaemia. Polytrauma patients with diabetes have a significantly greater risk of mortality than patients who do not have diabetes. Non-union of fractures is more common in patients with diabetes, as are deep-seated postoperative infections. National guidelines from the Joint British Diabetes Societies for Inpatient Care advise how to manage patients with diabetes in the perioperative period. Trauma and orthopaedic surgeons must be aware of these increased risks of operating and ensure that patients are involved in surgical decision making.


"Unavoidable Satisfactions": The Analyst's Pleasure.
Analysts have often described their work as depriving, painful, and hard to endure, while its pleasures have been the subject of little commentary. The real history and ongoing temptations of boundary violation long ago made the gratifications of psychoanalytic work a matter of anxiety. Analysts' pleasure in their work was problematized. Some of this problematizing is necessary because of real risk, but much of it is not only unnecessary but misleading and destructive. Psychoanalysts pursue achievement of a unique form of human intimacy, yet acquired habits of professional modesty and humility have encouraged the illusion that analyzing can occur without desire or ambition on the analyst's part. These habits have made it difficult for analysts to openly discuss what they get from the intimacy of analyzing that yields its pleasures. Our field demands that analysts deny that the work provides much more than pain (at least until the conclusion of an analysis), but psychoanalysis both misunderstands and misrepresents itself if we cannot speak of the distinctly broad range of pleasures available in analyzing.


Synthesis of specific SPECT-radiopharmaceutical for tumor imaging based on methionine: 99mTc-DTPA-bis(methionine).
Methionine-diethylenetriaminepentaaceticacid-methionine [DTPA-bis(Met)] was synthesized by covalently conjugating two molecules of methionine (Met) to DTPA and was labeled with (99m)Tc in high radiochemical purity and specific activity (166-296 MBq/micromol). Kinetic analysis showed K(m) of 12.95 +/- 3.8 nM and a maximal transport rate velocity (V(max)) of 80.35 +/- 0.42 pmol microg protein(-1) min(-1) of (99m)Tc-DTPA-bis(Met) in U-87MG cells. DTPA-bis(Met) had dissociation constants (K(d)) of 0.067 and 0.077 nM in U-87MG and BMG, respectively. (35)S-methionine efflux was trans-stimulated by (99m)Tc-labeled DTPA conjugate demonstrating concentrative transport. The blood kinetic studies showed fast clearance with t(1/2) (F) = 36 +/- 0.5 min and t(1/2) (S) = 5 h 55 min +/- 0.85 min. U-87MG and BMG tumors saturated at approximately 2000 +/- 280 nmol/kg of (99m)Tc-DTPA-bis(Met). Initial rate of transport of (99m)Tc-DTPA-bis(Met) in U-87MG tumor was found to be 4.68 x 10(-4) micromol/kg/min. The tumor (BMG cell line, malignant glioma) grafted in athymic mice were readily identifiable in the gamma images. Semiquantitative analysis from region of interest (ROI) placed over areas counting average counts per pixel with maximum radiotracer uptake on the tumor was found to be 11.05 +/- 3.99 and compared ROI with muscle (0.55 +/- 0.13). The tumor-to-contralateral muscle tissue ratio of (99m)Tc-DTPA-bis(Met) was found to be 23 +/- 3.3. Biodistribution revealed significant tumor uptake and good contrast in the U-87MG, BMG, and EAT tumor-bearing mice. In clinical trials, the sensitivity, specificity, and positive predictive values were found to be 87.8%, 92.8%, and 96.6%, respectively. (99m)Tc-DTPA-bis(Met) showed excellent tumor targeting and has promising utility as a SPECT-radiopharmaceutical for imaging methionine-dependent human tumors and to quantify the ratio of MET(+)/HCY(-).


IVIG- responsive multiple cranial neuropathy: a pharyngo-facial variant of Guillain-Barré syndrome.
We report a case with symptoms of facial swelling, bilateral facial paralysis, dysphagia and aspiration. On electrophysiological studies, the right facial nerve was not excitable. The left facial nerve compound muscle action potential (CMAP) amplitude was severely dispersed and latency was mildly prolonged, consistent with demyelination. Cerebrospinal fluid examinations were normal. Anti-ganglioside antibodies and tumor markers were negative. Bickerstaff brainstem encephalitis, stroke, diabetes mellitus, vasculitis, sarcoidosis, Sjögren's syndrome, Melkersson-Rosenthal Syndrome, trauma, infectious diseases, toxicity, neoplasm, facial onset sensory and motor neuronopathy (FOSMN) and other degenerative diseases were excluded. Intravenous immunoglobulin therapy resolved symptoms of lower cranial nerve dysfunction. Clinically incomplete improvement of bilateral facial paralysis was observed. We conclude that IVIg therapy may improve the symptoms of multiple cranial nerve palsies due to pharyngo-facial variant of Guillain-Barré syndrome.


Durable mixed allogeneic chimerism and tolerance by a nonlethal radiation-based cytoreductive approach.
For over 40 years, the association between hemopoietic chimerism and donor-specific tolerance for allografts has been recognized. However, toxicity associated with lethal conditioning has prevented the clinical application of bone marrow (BM) chimerism to induce tolerance. We previously demonstrated that engraftment could be achieved with less than total recipient myeloablation (700 cGy) and that the incidence of engraftment correlated with the dose of total body irradiation (TBI). Administration of cyclophosphamide (CyP) on Day +2 reduced the minimum TBI dose sufficient to permit engraftment to 500 cGy. In the current study, addition of antilymphocyte globulin (ALG) to the TBI/CyP-based conditioning approach reduced the radiation required for engraftment to < or = 300 cGy. B10 (H-2b) mice conditioned with ALG on day -3, 300 cGy of TBI with transplantation of B10.BR (H-2k) or BALB/c (H-2d) BM on day 0, and CyP on day +2 exhibited evidence of donor chimerism (49.6 +/- 3.7% and 38.2 +/- 2.4%, respectively) in 97% of recipients. ALG eliminated CD4+ and CD8+ cells and decreased NK1.1+ cells in the peripheral circulation at the time of transplantation. Moreover, T and NK cells in the host BM were significantly decreased compared with cells of recipients conditioned with TBI alone. CyP delayed repopulation of host thymocytes, providing time for the establishment of donor chimerism before production of mature T cells. Chimeric animals exhibited stable multilineage chimerism and donor-specific tolerance to skin grafts and in in vitro assays. This model may provide a clinically acceptable approach for the induction of donor-specific transplantation tolerance.


[Measurement and data analysis of drug concentrations at the target site--potentials, limitations and fields of application].
Drug measurements in the blood are only surrogates for drug concentrations in peripheral tissues, which often represent the target sites of the drug. Due to drug specific and physiological characteristics, however, blood and target site concentrations may differ. For this reason, methods to measure drug concentrations at the target site have been developed during the last years. During the last decade, microdialysis has become the method of choice for the continuous study of unbound tissue concentrations of drugs. In order to fully exploit these measurements to quantify the concentration-time profile of the investigated drug, different tools of data analysis can be applied. The aim is to contribute to decision-making in selecting the optimal dose 1) for dosing schedules during the development program of new drugs and 2) for therapeutic usage for physicians and pharmacists. For these aims, the so called ,,nonlinear mixed effect (NLME) modelling approach" presents the method of choice as it determines the typical concentration-time profile of a drug as well as the variability within the investigated study population. Additionally, between-patient variability can be explained by patient-specific characteristics e.g. weight enabling dose individualisation within the whole investigated population. A systematic literature research in Pubmed for the use of antiinfectives in humans shows that the preferable methods of measuring concentrations at the target site (microdialysis) and data analysis (NLME) have rarely been used simultaneously. Hence, in future the benefit of linking both methods of choice should be further exploited in order to improve knowledge gain, to optimise antiinfective dosing regimens and to increase medication safety.


Multimodal Intraoperative Monitoring During Microsurgical Treatment of Spinal Dural Arteriovenous Fistula.
We report here a case to illustrate the potential intraoperative multimodal monitoring options available for safe ligation of spinal dural arteriovenous fistula (DAVF). The success of microsurgical treatment depends on the correct identification of the arterial feeder and monitoring the functional integrity of the corticospinal tract.


Synthesis of novel hybrid molecules from precursors with known antiparasitic activity.
Three novel new compounds derived from antiparasitic precursors have been synthesized and tested for their antiamoebic and antigiardial activities. The condensation of 2-(2-methyl-5-1H-nitroimidazolyl)ethylamine (6) with 5-nitro-2-furylacrylic acid (7) gave 3-(5-nitrofuran-2-yl)-N-[2-(5-nitroimidazol-1-yl)ethyl]acrylamide (8). Condensation of 7 with 7-chloro-4-(piperazin-1-yl)quinoline (9) afforded 1-[4-(7-chloroquinolin-4-yl)piperazin-1-yl)-3-(5-nitrofuran-2-yl)propenone as a mixture of two isomers; 10-a (the E-isomer) and 10-b (the Z-isomer). In addition, the reaction of 9 with 1-(2-bromoethyl)-2-methyl-5-nitroimidazole (11) in the presence of K(2)CO(3) and NaI yielded 7-chloro-4-(4-[2-(5-nitroimidazol-1-yl)ethyl]-piprazin-1-yl)quinoline (12). On the basis of preliminary screening data for these new compounds, compound 12 exhibited potent lethal activities against Entamoeba histolytica and Giardia intestinalis; its IC(50) (about 1 microM) was lower, at least by a factor of five, compared to the standard drug, metronidazole. In addition, the IC(50) of compound 12 against the tested parasites is 600 times below that against Hep-2 and Vero cells. Compounds 8 and 10-a also exhibited potent or moderate antiamoebic and antigiardial activities with IC(50 values) of about 5.5 microM, and 140 microM, respectively, against the tested parasites. These two hybrid molecules, 8, 10-a, were also non-cytotoxic at the lethal concentrations against the parasites.


Hamming-shifting graph of genomic short reads: Efficient construction and its application for compression.
Graphs such as de Bruijn graphs and OLC (overlap-layout-consensus) graphs have been widely adopted for the de novo assembly of genomic short reads. This work studies another important problem in the field: how graphs can be used for high-performance compression of the large-scale sequencing data. We present a novel graph definition named Hamming-Shifting graph to address this problem. The definition originates from the technological characteristics of next-generation sequencing machines, aiming to link all pairs of distinct reads that have a small Hamming distance or a small shifting offset or both. We compute multiple lexicographically minimal k-mers to index the reads for an efficient search of the weight-lightest edges, and we prove a very high probability of successfully detecting these edges. The resulted graph creates a full mutual reference of the reads to cascade a code-minimized transfer of every child-read for an optimal compression. We conducted compression experiments on the minimum spanning forest of this extremely sparse graph, and achieved a 10 - 30% more file size reduction compared to the best compression results using existing algorithms. As future work, the separation and connectivity degrees of these giant graphs can be used as economical measurements or protocols for quick quality assessment of wet-lab machines, for sufficiency control of genomic library preparation, and for accurate de novo genome assembly.


Emerging Biomarkers Beyond Leukotrienes for the Management of Nonsteroidal Anti-inflammatory Drug (NSAID)-Exacerbated Respiratory Disease.
Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) is a unique condition characterized by aspirin/NSAID hypersensitivity, adult-onset asthma, and/or chronic rhinosinusitis with nasal polyps. Arachidonic acid metabolism dysregulation and intense eosinophilic/type 2 inflammation are central mechanisms in NERD. Studies have been conducted on various biomarkers, and urinary leukotriene E4 is considered the most available biomarker of NERD. However, the pathophysiology of NERD is heterogeneous and complex. Epithelial cells and platelets can interact with immune cells in NERD, and novel biomarkers related to these interactions have recently been investigated. We summarize emerging novel biomarkers of NERD and discuss their roles in the management of NERD.


Gene-Activated Matrix with Self-Assembly Anionic Nano-Device Containing Plasmid DNAs for Rat Cranial Bone Augmentation.
We have developed nanoballs, a biocompatible self-assembly nano-vector based on electrostatic interactions that arrange anionic macromolecules to polymeric nanomaterials to create nucleic acid carriers. Nanoballs exhibit low cytotoxicity and high transfection efficiently in vivo. This study investigated whether a gene-activated matrix (GAM) composed of nanoballs containing plasmid (p) DNAs encoding bone morphogenetic protein 4 (pBMP4) could promote bone augmentation with a small amount of DNA compared to that composed of naked pDNAs. We prepared nanoballs (BMP4-nanoballs) constructed with pBMP4 and dendrigraft poly-L-lysine (DGL, a cationic polymer) coated by γ-polyglutamic acid (γ-PGA; an anionic polymer), and determined their biological functions in vitro and in vivo. Next, GAMs were manufactured by mixing nanoballs with 2% atelocollagen and β-tricalcium phosphate (β-TCP) granules and lyophilizing them for bone augmentation. The GAMs were then transplanted to rat cranial bone surfaces under the periosteum. From the initial stage, infiltrated macrophages and mesenchymal progenitor cells took up the nanoballs, and their anti-inflammatory and osteoblastic differentiations were promoted over time. Subsequently, bone augmentation was clearly recognized for up to 8 weeks in transplanted GAMs containing BMP4-nanoballs. Notably, only 1 μg of BMP4-nanoballs induced a sufficient volume of new bone, while 1000 μg of naked pDNAs were required to induce the same level of bone augmentation. These data suggest that applying this anionic vector to the appropriate matrices can facilitate GAM-based bone engineering.


Report of a fatal case of pulmonary thromboembolism in a long-distance truck driver.
Long-distance truck drivers have been found to be associated with many medical problems because of their lifestyle and work environment. Many studies have revealed an increased risk in sexually transmitted infections, musculoskeletal disease, sleep disorders, hypertension, gastrointestinal disease, substance abuse and alcoholism, lung cancer, as well as human immunodeficiency virus infection. To our knowledge, there are no any articles about a fatal case of pulmonary thromboembolism. We report a case of a 45-year-old truck driver, who was found dead in his truck at a service station along the A1 motorway in Umbria, Italy. Autopsy findings revealed pulmonary thromboembolism as cause of death. Our report underlies that future actions must be addressed to provide health care access to this vulnerable, medically underserved population.


[Clinical importance of laboratory tests in rheumatology].
Knowledge of mechanisms of rheumatic diseases has a continuing influence on the introduction of many laboratory tests to be used for establishing diagnosis or monitoring the activity of rheumatic disease. In the article presented are autoantibodies characteristic for distinct inflammatory rheumatic diseases, the role of serum complement activity, immune complexes, HLA-typing as well as other laboratory parameters needed for the diagnosis of rheumatic disease. The methods of synovial fluid analysis are described. Presented are laboratory investigations used by rheumatologists for the evaluation of activity of inflammatory rheumatic diseases and successful treatment together with investigations necessary for the evaluation of side-effects of treatment.


Pooling saliva samples as an excellent option to increase the surveillance for SARS-CoV-2 when re-opening community settings.
In many countries a second wave of infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has occurred, triggering a shortage of reagents needed for diagnosis and compromising the capacity of laboratory testing. There is an urgent need to develop methods to accelerate the diagnostic procedures. Pooling samples represents a strategy to overcome the shortage of reagents, since several samples can be tested using one reaction, significantly increasing the number and speed with which tests can be carried out. We have reported the feasibility to use a direct lysis procedure of saliva as source for RNA to SARS-CoV-2 genome detection by reverse transcription quantitative-PCR (RT-qPCR). Here, we show that the direct lysis of saliva pools, of either five or ten samples, does not compromise the detection of viral RNA. In addition, it is a sensitive, fast, and inexpensive method that can be used for massive screening, especially considering the proximity of the reincorporation of activities in universities, offices, and schools.


Genes of major histocompatibility complex class II influence chronic C hepatitis treatment with interferon in hemodialysis patients.
The prevalence of anti-HCV among patients on hemodialysis is consistently higher than in the general population, indicating that patients on hemodialysis programs are at risk of acquiring HCV infection. The response to interferon alpha 2b (IFN -alpha 2b) therapy in chronic C hepatitis depends on viral and host factors. We treated 22 chronic C hepatitis uremic patients with IFN -alpha 2b (3 MU three times a week) and compared interferon responsive and unresponsive patients with regard to HLA II genes. HLA II genes were investigated by PCR-SSP low resolution, anti-HCV with ELISA II and HCV-RNA with reverse transcriptase "nested" PCR. HLA DRB1*13 is 50% positive in the non-responder group (four women, four men, mean age; 28.8+/-11.9 years) and 7% in the responder group (five women, nine men, mean age; 32.2+/-7.8 years) (p<0.05). There was no difference with respect to HLA genes between controls (six women, eight men, mean age; 29.5+/-12.8 years) and patients (nine women, 13 men, mean age; 31.0+/-9.3 years) (HLA DRB1*13 is 28% and 22% positive, respectively). We conclude that major histocompatibility complex class II genes influence the outcome of chronic C hepatitis treatment with IFN -alpha 2b.


Differential antibiotic-induced endotoxin release in severe melioidosis.
Severe melioidosis is a life-threatening, systemic bacterial infection caused by Burkholderia pseudomallei. A prospective, randomized treatment trial was conducted in northeast Thailand to compare ceftazidime (a penicillin-binding protein [PBP]-3-specific agent that causes release of large amounts of endotoxin in vitro) and imipenem (a PBP-2-specific agent that kills B. pseudomallei more rapidly but releases low amounts of endotoxin) in severe melioidosis over a 6-h time course after the first dose of antibiotic. Despite similar clinical, microbiological, endotoxin, and cytokine measures at study entry, ceftazidime-treated patients (n=34) had significantly greater systemic endotoxin (P<.001) than patients treated with imipenem (n=34) after the first dose of antibiotic. No overall difference in mortality was observed (35% in both groups [95% confidence interval, 20%-50%]). Differential antibiotic-induced endotoxin release is demonstrable in severe melioidosis. These differences in endotoxin release did not appear to have a significant impact on survival in this group of patients.


A determination of the optimum beam ratio to produce maximum contrast photographic reconstructions from double-exposure holographic interferograms.
The beam ratio (reference beam intensity to object beam intensity) which produces maximum contrast photographic reconstructions from double-exposure holographic interferograms was experimentally determined to be 1.2 +/- 0.2.


Dual Antibacterial and Anticancer Activity of 4-Benzoyl-1-dichlorobenzoylthiosemicarbazide Derivatives.
A group of 4-benzoyl-1-dichlorobenzoylthiosemicarbazides endowed with antibacterial activity was evaluated for its cytotoxic properties against breast cancer cells (MCF-7, MDA-MB-231) and head and neck squamous cell carcinomas (FaDu, SCC-25). Cytotoxicity of the investigated compounds was measured using MTT and [3H]-thymidine incorporation bioassays. 1-(2,3-Dichlorobenzoyl)-4-(2-methylbenzoyl)thiosemicarbazide (TA-4), 1-(2,4-dichlorobenzoyl)- 4-(2-methylbenzoyl)thiosemicarbazide (TA-18), and 1-(2,4-dichlorobenzoyl)-4-(4-nitrolbenzoyl)- thiosemicarbazide (TA-20) were found to possess anticancer activity equipotent or even stronger than that of reference drug - etoposide. In order to clarify the molecular mode of action of the mentioned compounds, the relaxation assay kit for human DNA topoisomerase II was used. It turned out that reduction of viability of cancer cells was a result of inhibition of human DNA topoII. Molecular docking studies proved that 4-benzoyl-1-dichlorobenzoylthiosemicarbazides strongly interact with DNAdependent subunit of that enzyme.


Should we hail the Red King? Evolutionary consequences of a mutualistic lifestyle in genomes of lichenized ascomycetes.
The Red Queen dynamic is often brought into play for antagonistic relationships. However, the coevolutionary effects of mutualistic interactions, which predict slower evolution for interacting organisms (Red King), have been investigated to a lesser extent. Lichens are a stable, mutualistic relationship of fungi and cyanobacteria and/or algae, which originated several times independently during the evolution of fungi. Therefore, they represent a suitable system to investigate the coevolutionary effect of mutualism on the fungal genome. We measured substitution rates and selective pressure of about 2000 protein-coding genes (plus the rDNA region) in two different classes of Ascomycota, each consisting of closely related lineages of lichenized and non-lichenized fungi. Our results show that independent lichenized clades are characterized by significantly slower rates for both synonymous and non-synonymous substitutions. We hypothesize that this evolutionary pattern is connected to the lichen life cycle (longer generation time of lichenized fungi) rather than a result of different selection strengths, which is described as the main driver for the Red Kind dynamic. This first empirical evidence of slower evolution in lichens provides an important insight on how biotic cooperative interactions are able to shape the evolution of symbiotic organisms.


Supernumerary ectopic parathyroid glands. Persistent hyperparathyroidism due to mediastinal parathyroid adenoma localized by preoperative single photon emission computed tomography and intraoperative gamma probe application.
Ectopic and/or supernumerary parathyroid glands are a major cause of persistent and recurrent Hyperparathyroidism (HPT). For this reason, it is widely accepted that preoperative localization should be performed to improve the surgical results in patients with persistent or recurrent HPT. Primary HPT (pHPT) was diagnosed incidentally in a 50-year old female patient during a preoperative examination for hernia. No pathologic parathyroid gland was detected in the preoperative Tc-99m Methoxybutylisonitrile (MIBI) scintigraphy and Ultrasonography (US). Cervical exploration was performed bilaterally. Four parathyroid glands were located adjacent to the thyroid gland. A fifth was detected in front of the cricoid cartilage. All five of them were of normal histology. Postoperatively, hypercalcemia persisted. Single Photon Emission Computed Tomography (SPECT) was performed before the second operation and radioguide surgery was carried out by median sternotomy. SPECT showed a parathyroid adenoma in the middle of the anterior mediastinum which was excised (size 1x0.5x0.5 cm) using a gamma probe. In conclusion, SPECT and intraoperative gamma probe application may help to detect the parathyroid adenomas, especially if they are small in size and buried in the adipose tissue. Such localization shortens the duration of the operation and reduces the possibility of complications.


Hepatocellular carcinoma occurring in a patient with Crohn's disease treated with both azathioprine and infliximab.
Hepatocellular carcinoma is known to be associated with underlying liver diseases, such as cirrhosis, hemochromatosis, and chronic viral hepatitis. All reported cases of hepatocellular carcinoma in association with Crohn's disease involve patients treated previously with azathioprine or both azathioprine and steroids. However, hepatocellular carcinoma associated with the use of azathioprine and infliximab has not been reported. In this report, we describe an unusual case of hepatocellular carcinoma and focal hepatic glycogenosis (FHG) occurring in a non-cirrhotic Crohn's disease patient who has been treated with both azathioprine and infliximab.


Meniscal ossicle: a case report.
Meniscal ossicle is a cortical or cancellous tissue with central viable marrow surrounded by meniscal cartilage. We present a case of medial meniscal ossicle at its posterior horn. A 21-year-old male military recruit visited our clinic due to left knee discomfort. He had not undergone any notable injury on the knee, but complained of intermittent catching or giving way without locking. Simple radiographs showed a small round bony fragment at posteromedial side of knee joint. The magnetic resonance imaging revealed an intra-substance lesion of meniscus, whose signal is identical to bone. On arthroscopy, the articular cartilage of medial femoral condyle and tibial plateau appeared degenerative with a groove-like scar. The medial meniscus seemed swollen at the posterior horn, but there was no discernible tear in the adjacent meniscus. After piecemeal removal of meniscal substance, a small osseous fragment was identified, which was evacuated via posteromedial portal. The resection of meniscus amounted to a subtotal meniscectomy. The activities of daily living were possible without any trouble even after 9 months of follow-up. This entity should be distinguished from intra-articular loose body, and included in the differential diagnosis of the incidental findings of small ossified density around knee joint.


Clinical and pathologic features of hepatocellular carcinoma in young and older Italian patients.
It is not known whether putative etiologic factors and clinical and pathological features of hepatocellular carcinoma (HCC) differ between young adult and older white patients. We examined the characteristics of 498 consecutive patients with HCC age < 50 years (Group 1: 54 patients) and age > or = 50 (Group 2: 444 patients), an age beyond which the tumor occurrence rate briskly increases. Demographic characteristics, alcohol and coffee intake, and cigarette smoking did not differ between the two groups. Group 1 had a greater prevalence of the hepatitis B surface antigen (HBsAg) carriers (P = 0.006), while the prevalence of either past hepatitis B virus infection (P = 0.008) or antivirus C antibodies (P = 0.016) was higher in Group 2. The lack of both hepatitis B and C virus serologic markers was more common in Group 1 (P = 0.018). In these patients, HCC was less frequently superimposed on cirrhosis (P = 0.002) and was more advanced at the time of diagnosis. In fact, despite a better histologic differentiation grade (P = 0.019), monofocal (solitary and massive) tumors were larger (P = 0.012), small lesions (< or = 5 cm) less frequent (P = 0.028), and either diffuse (P < 0.001) or massive (P = 0.011) types more common. An elevation of serum alpha-fetoprotein was less frequent in group 1 (P = 0.016), but this difference disappeared when the "diagnostic" cut-off of 400 ng/mL was considered. Albeit the prevalence of presenting symptoms did not significantly differ between the two groups, the clinical stage was more advanced in young patients (P = 0.004). The 9-year cumulative rate of survival was similar in the 2 groups. An early exposure to the virus and/or an accelerated hepatocarcinogenesis in HBsAg carriers can be inferred. Moreover, in the period of life at low risk for hepatoma: (1) the impact of nonalcoholic chemical carcinogenesis seems to be greater; (2) the tumor occurrence is less dependent on cirrhosis development; (3) although histologically better differentiated, the neoplasm is more advanced at the time of diagnosis; and (4) the long term survival is similar to that of the patients age 50 years or older.


Coordinate regulation of malonyl-CoA decarboxylase, sn-glycerol-3-phosphate acyltransferase, and acetyl-CoA carboxylase by AMP-activated protein kinase in rat tissues in response to exercise.
Changes in the concentration of malonyl-CoA in many tissues have been related to alterations in the activity of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in its formation. In contrast, little is known about the physiological role of malonyl-CoA decarboxylase (MCD), an enzyme responsible for malonyl-CoA catabolism. In this study, we examined the effects of voluntary exercise on MCD activity in rat liver, skeletal muscle, and adipose tissue. In addition, the activity of sn-glycerol-3-phosphate acyltransferase (GPAT), which like MCD and ACC can be regulated by AMP-activated protein kinase (AMPK), was assayed. Thirty min after the completion of a treadmill run, MCD activity was increased approximately 2-fold, malonyl-CoA levels were reduced, and ACC and GPAT activities were diminished by 50% in muscle and liver. These events appeared to be mediated via activation of AMPK since: 1) AMPK activity was concurrently increased by exercise in both tissues; 2) similar findings were observed after the injection of 5-amino 4 imidazole carboxamide, an AMPK activator; 3) changes in the activity of GPAT and ACC paralleled that of MCD; and 4) the increase in MCD activity in muscle was reversed in vitro by incubating immunoprecipitated enzyme from the exercised muscle with protein phosphatase 2A, and it was reproduced by incubating immunopurified MCD from resting muscle with purified AMPK. An unexpected finding was that exercise caused similar changes in the activities of ACC, MCD, GPAT, and AMPK and the concentration of malonyl-CoA in adipose tissue. MCD, GPAT, and ACC are coordinately regulated by AMPK in liver and adipose tissue in response to exercise, and except for GPAT, also in muscle. The results suggest that AMPK activation plays a major role in regulating lipid metabolism in many cells following exercise. They also suggest that in each of them, it acts to increase fatty acid oxidation and decrease its esterification.


The significance of microbial cultures of the hematopoietic support for patients receiving high-dose chemotherapy.
The use of hematopoietic support for patients receiving high-dose chemotherapy has increased over the past 10 years. Various quality controls are performed on the hematopoietic cells, including microbiologic cultures. There is considerable expense associated with the serial cultures performed at different times during the collection, processing, and use of the cells. We reviewed all the microbiologic cultures performed on bone marrow harvests and leukaphereses over a 17 month period. Of the 227 bone marrow harvests, 16 cultures were positive, but only 3 (1.3%) were repeat positives with the same organism after processing or at the time of reinfusion. Of the 560 leukaphereses, 4 (0.7%) were cultured positive at the time of collection and reinfusion. Two patients were bacteremic with gram-negative bacilli at the time of leukaphereses despite being asymptomatic, and these were the only two products that had to be collected again. No patient suffered an adverse clinical result after receiving culture-positive cells. Bone marrow and peripheral blood progenitor cells can be safely collected, and a culture after processing is adequate to ensure the safety of the product.


Gentamicin volume of distribution in critically ill septic patients.
Gentamicin intrapatient pharmacokinetics variations were studied in 40 critically ill medical patients, suffering gram-negative sepsis. These patients were studied in two phases throughout gentamicin treatment: firstly, on the second day of treatment, when aggressive fluid therapy was required, and secondly, five days later, when patients had achieved a more stable clinical condition. Pharmacokinetic parameters were determined using least squares linear regression analysis assuming a one-compartment model using the Sawchuk-Zaske method. The apparent volume of distribution (Vd) in the first phase of the study was 0.43 +/- 0.12 L/kg, while on the seventh day of treatment it was 0.29 +/- 0.17 L/kg (p less than 0.001). Statistically significant differences were also observed for peak serum concentration (p less than 0.001), total dosage recommended (p less than 0.001) and half-life (p less than 0.05), whilst differences were not found for trough levels. From the analysis of the results obtained, we recommend increasing the initial dosage and monitoring plasma levels within the first days of therapy in critically ill patients treated with gentamicin, since important variations in aminoglycoside Vd related to disease, fluid balance and renal function, commonly occur in these patients.


Hammerhead Ribozymes Suppress HBV(adr) in HepG2 Cells.
Three hammerhead ribozymes (RS3, RC2 and RC1) targeting to the HBV genome have been designed. Plasmids were constructed by inserting the genes of naked and tRNA-embedded ribozymes into RNA trimming vector pRG523 and then were transferred to eukaryotic expression vector. By the similar cloning method the shotgun-type plasmids carrying homogeneous RS3 or RtS3 unitconnected in tandem were obtained. After co-transfecting the above plasmids and HBV genome containing plasmid into human hepatoma cell line HepG2 respectively and selection by G418, the HBV-inhibiting activity of different kinds of ribozyme in G418-resistant cells was achieved by measuring the decrease of HBV-RNA, progeny DNA and the antigens expressed. The results showed that all the ribozymes were active with more than 70% inhibition activity against the HBV and that tRNA-embedded ribozymes had higher activity than naked ribozymes. It is worth particular interest that shotgun-type ribozymes with the connected unit in tandem with 8 and 12 units constructed in the plasmid revealed the highest activity, reaching >90% inhibition.


The role of diabetes mellitus in the effectiveness of intradialytic exercise intervention on patients' muscle function.
The purpose of this study is to identify the role of diabetes mellitus in the effectiveness of intradialytic exercise intervention among haemodialysis patients. In this multicentre study 90 dialysed patients were allocated to the experimental (EXG, n=57) or control group (CNG, n=33). In EXG, we included 20 diabetic and 37 non-diabetic patients. In CNG, we enrolled 8 diabetic and 25 non-diabetic patients. EXG underwent a 12-week supervised, progressive, intradialytic resistance training programme, while CNG stayed inactive during dialysis. Baseline, post-interventional and post-follow-up assessments of maximal force during hip extension (HE), hip flexion (HF) and knee extension (KE) contractions were completed in both groups of patients. HE increased in diabetic and non-diabetic EXG patients (diabetic EXG, change: +14.5N; 95% CI=-5.5 to +34.5; non-diabetic EXG, +18.6N; 95% CI=+3.4 to +33.8) and diabetic CNG patients (change: +17.9N; 95% CI=-9.2 to +44.9). Only non-diabetic CNG patients experienced a decrease in HE (change: -22.8N; 95% CI=-36.9 to -8.7, P<.05). Resistance training improved muscle function among dialysis patients regardless of the presence of diabetes mellitus. We found that non-diabetic patients lose their muscle function extensively during inactivity, while diabetic patients retain their muscle function.


Ileus and intestinal obstruction--ultrasonographic findings as a guideline to therapy.
Between September 1, 1982 and January 31, 1986, a study was undertaken in a total of 111 patients to assess the efficacy of ultrasonography in diagnosing intestinal obstruction and ileus. In 109 cases (98%), ultrasonography provided the correct diagnosis. In one case, obstruction was correctly suspected. In another case, the diagnosis was false negative. In 51 cases (46%), ultrasonography yielded the causative diagnosis. Ultrasonography was especially rewarding in the diagnosis of X-ray-negative intestinal obstruction, very high obstruction, clinically concealed incarcerated femoral hernias and in the differentiation of intestinal obstruction and ileus in the postoperative course. Ultrasonographic differential diagnosis was a reliable guideline for adequate treatment modalities in pertinent cases, thus contributing to therapeutic success.


Treatment and outcomes in undifferentiated and dedifferentiated endometrial carcinoma.
Undifferentiated and dedifferentiated endometrial carcinoma is a rare type of uterine malignancy. This study assesses disease characteristics, treatment and survival outcomes in patients with undifferentiated and dedifferentiated endometrial carcinoma treated at BC Cancer. All patients diagnosed with undifferentiated and dedifferentiated endometrial carcinoma between 2000 and 2019 at BC Cancer were reviewed centrally. Clinical, pathologic, treatment and outcomes were reviewed retrospectively. The Kaplan-Meier method was used to evaluate overall survival (OS) and disease-free survival (DFS). Multivariable analysis was performed using Cox regression analysis. Fifty-two patients were included, 33% had undifferentiated carcinoma and 67% dedifferentiated carcinoma. Sixty-nine percent of those who had mismatch repair (MMR) testing of their tumor had an abnormal profile. The 5-year DFS was 80% (95% confidence interval [CI]=71%-89%) for stage I/II, 29% (95% CI=28%-40%) for stage III and 10% (95% CI 1%-19%) for stage IV. The 5-year OS was 84% (95% CI=75%-92%) for stage I/II, 38% (95% CI=26%-50%) for stage III and 12% (95% CI=1%-24%) for stage IV. Multivariate analysis showed that receiving adjuvant chemotherapy, adjuvant radiotherapy, lower stage and better Eastern Cooperative Group performance status were associated with improved DFS (p<0.05). Patients with stage I/II undifferentiated and dedifferentiated endometrial carcinoma had excellent survival outcomes, those with stage III/IV had worse outcomes, similar to previously reported. Adjuvant chemotherapy and radiotherapy were associated with improved DFS. MMR testing should be performed for these patients due to the high incidence of abnormal profiles.


Neuropsychological characteristics of Huntington's disease carriers: a double blind study.
A cohort of 33 people at risk for Huntington's disease (HD), applying for genetic testing, were tested with a battery of neuropsychological tests covering attentional, visuospatial, learning, memory, and planning functions. A psychiatric rating scale, SCL-90R, was also applied, mainly as a control, since cognitive dysfunction could be ascribed to functional disorders as well as neurodegenerative processes. Self-rating did not indicate any psychiatric symptoms in carriers or non-carriers. However, significantly inferior cognitive functioning in the gene carriers was disclosed by the neuropsychological tests. Primarily, attentional, learning, and planning functions were affected. It is concluded that premorbid cognitive decline occurs in HD.


Integration of foreign DNA in an intergenic region of the archaeon Methanosarcina mazei without effect on transcription of adjacent genes.
Transformation systems for methanogenic archaea are scarce, none has been reported for the genus Methanosarcina, and plasmids useful as vectors for cloning foreign DNA into methanogens that stably replicate as extrachromosomal elements are not available. We developed an integration vector for transformation of a member of the genus Methanosarcina, i.e. Methanosarcina mazei, using a segment (Int alpha; 1015 bp) which encompasses the intergenic region (431 bp) between the stress (heat-shock) genes grpE and dnaK. This segment also includes the 3' end (270 bp) of the grpE protein-coding region and the 5' end (314 bp) of the dnaK protein-coding region. Int alpha has an EcoRI site, useful for cloning, situated in the 3' direction beyond the grpE transcription termination region, and far upstream from the dnaK promoter. This location of the site, and the monocistronic mode of transcription of grpE and dnaK in M. mazei, suggested to us that a foreign insert in the site would not affect transcription of either flanking gene. A puromycin-resistance cassette (pac cassette) was inserted in the EcoRI site of Int alpha already inserted in pUC18, to obtain a vector which integrated the pac cassette in the chromosome between grpE and dnaK. The pac gene was transcribed and the transformants acquired puromycin resistance. Constitutive and heat-shock-induced transcription of grpE and dnaK in the transformants was the same as in wild-type cells. The two vectors found with transforming ability differed in the orientation of the pac cassette but both had M. mazei's DNA on each flank of the cassette, with the same orientation as that of the homologous segments in the chromosome.


[Diarrhea in a patient with Down syndrome and endemic sprue].
Down syndrome is associated with disorders such as celiac disease, hypothyroidism, and insulin-dependent diabetes mellitus. In patients with mono- or oligosymptomatic celiac disease the time interval between the onset of symptoms and diagnosis often is unacceptably long. A female patient with Down syndrome is presented who had acute watery diarrhea, which spontaneously ceased but recurred after a few days. After endoscopic and histologic evaluation and measurement of gliadin, endomysium, and reticulin antibodies celiac sprue was diagnosed. Further investigation showed findings of autoimmune hypothyroidism and secondary hyperparathyreoidism. After the patient was put on a gluten-free diet her state quickly improved. Associations between Down syndrome and autoimmune diseases exist. Patients with acute gastrointestinal symptoms should be evaluated as to celiac disease. The time interval between the onset of symptoms and diagnosis of celiac disease can be shortened, if all diagnostic tools are used at the appropriate time.


Silent celiac disease in chronic hepatitis C: impact of interferon treatment on the disease onset and clinical outcome.
To assess the impact of interferon treatment on celiac disease onset in hepatitis C patients and to clarify its clinical relevance and outcome. Hepatitis C is associated with autoimmunity, which can be exacerbated by interferon treatment. Cases of celiac disease activation during interferon treatment have been reported. Retrospective evaluation of 534 hepatitis C patients with or without symptoms compatible with celiac disease onset during interferon treatment and 225 controls. Anti-transglutaminase antibodies were assayed. HLA-DQA1 and -B1 loci were typed. Upper gastrointestinal endoscopy was applied to confirm the diagnosis in antibody-positive patients. Anti-transglutaminase antibodies were detected before treatment in 1.3% of hepatitis C patients and in 0.4% of controls (not significant). Eighty-six percent of patients with anti-transglutaminase antibodies showed activation of celiac disease while on interferon. Symptoms ranged from mild to severe, and interferon had to be discontinued in 2 of 7 (29%) patients. Symptoms disappeared in 6 of 7 patients after interferon withdrawal. Onset of symptoms compatible with celiac disease during interferon therapy was significantly associated with the presence of anti-transglutaminase antibodies (OR 53). In hepatitis C patients, the activation of silent celiac disease during interferon treatment is almost universal and should be suspected, but it uncommonly requires interferon treatment discontinuation. Symptoms subside after interferon withdrawal.


Nicotine and alcohol dependence in patients with comorbid attention-deficit/hyperactivity disorder (ADHD).
Several studies have shown that attention-deficit/hyperactivity disorder (ADHD) represents a significant risk factor for the onset and development of an addiction. Thirty-five per cent of adult ADHD patients are known to be addicted to alcohol. Many ADHD patients also have an increased nicotine consumption, which typically, leads to an improvement of attention, ability to concentrate and control of impulses. There may be pathophysiological connections here. On the other hand, it can also be assumed that there is a high prevalence of addicted patients with undiagnosed ADHD. Ninety-one adult alcohol-dependent patients were examined for ADHD in this study, using the Wender Utah Rating Scale (WURS-k), Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) symptom check-list for ADHD and the Conners' Adult ADHD Rating Scales (CAARS, Long Version). The patients were divided into diagnostic sub-groups according to DSM-IV (inattentive type, impulsive type, combined type). Nicotine consumption was investigated using the Fagerström Test of Nicotine Dependence (FTND) and then graded as 'minimal', 'average' or 'high' nicotine dependence. There were 20.9% (WURS-k) or 23.1% (DSM-IV diagnostic criteria) of the patients addicted to alcohol, who showed evidence of ADHD in childhood. With the help of CAARS, it could be demonstrated that 33.3% of the patients who fulfilled the diagnostic criteria of ADHD, according to DSM-IV, had persisting ADHD in adulthood. The FTND showed a statistically significant difference in nicotine dependence between alcohol-dependent patients with and without ADHD in childhood. Patients numbering 76.2% with ADHD, demonstrated an 'average to high' level of nicotine dependence compared to 45.7% of those patients without ADHD. Furthermore, the number of patients not addicted to nicotine (19%) was significantly lower than among those without ADHD (36.6%) (P = 0.029). The results of this investigation reveal that a large number of ADHD patients suffer from alcohol dependence, and an even greater number from excessive nicotine dependence. The outcome indicates that there are most likely pathophysiological connections with alcohol and nicotine dependence, and that this substance abuse is probably a form of 'self-medication'. The results clearly underline the great importance of early and adequate diagnosis and therapy of ADHD, in order to prevent exacerbation of addictive illness.


Infection with Babesia canis in dogs in the Algiers region: Parasitological and serological study.
Canine babesiosis is a vector-borne disease transmitted by ticks of the Ixodidae family. The effects of infection in dogs can range from the subclinical to the severe lethal form. This study aimed to make an original contribution to the knowledge of circulating species of Babesia spp. in dogs in the region of Algiers as well as mechanisms and risk factors for their transmission. An epidemiological study was carried out on 189 blood samples taken from dogs from April 2015 to January 2016. The samples taken underwent parasitological by Giemsa-stained blood smear and serological analyzes by indirect fluorescent antibody test (IFAT). The ticks were looked on all the dogs taken. Giemsa-stained blood smears revealed the presence of two groups of parasites of the genus Babesia: Large Babesia (3/25, 12%) and small Babesia (22/25, 88%). The IFAT at a dilution of 1/32 showed an overall seroprevalence with Babesia canis of 17.98% (95% confidence interval 11.53-22.46). The distribution of the antibody titers for the positive samples showed that of the 34 positive sera with a titer ≥1/32, 28 sera remained positive at a dilution of 1/64 (14.81%), 22 at a dilution of 1/128 (11.64%) and 15 sera remained positive at a dilution of 1/256 (7.93%). Although seroprevalence varied according to canine population (20% and 19.49% in pet dogs and canine pound dogs, respectively, and 6.66-0% in farm dogs and hunting dogs, respectively), statistical analysis showed no significant differences between populations. The antibody titers obtained after several dilutions showed that 22 canine pound dog sera remained positive at a dilution of 1/128 compared to pet dogs and farm dogs which ceased to be positive at the dilution of 1/64. The comparison between the two diagnostic methods showed a strong agreement between the parasitological examination by blood smear and the serological method by IFAT. However, IFAT was much more sensitive. The analysis of risk factors, which may influence B. canis seroprevalence, has shown the influence of age, tick presence, and season. Finally, of the 242 ticks collected from a total of 59 dogs, only one tick species was identified , Rhipicephalus sanguineus. This study indicates a frequent circulation of species of Babesia in the dog in the Algiers region and R. sanguineus was the only tick identified.


Aged human skin removes UVB-induced pyrimidine dimers from the epidermis more slowly than younger adult skin in vivo.
Although many studies have been reported on the repair of ultraviolet light (UV)-induced cyclobutane-type pyrimidine dimers (CPDs) in DNA, the effects of aging on the removal of UV-induced CPDs from the human skin epidermis in vivo remains uncertain. Therefore, we employed immunoblotting and immunohistochemical methods using monoclonal antibodies (TDM-2) to CPDs to study age-related differences in the time required for the in vivo removal of UVB-induced CPDs. The flexure surfaces of the upper arms of five young men were exposed to UVB light at a fluence of 35 and 700 mJ/cm2, and four older men were also irradiated with the same doses of UVB mentioned above. Each area of skin was biopsied before and immediately after irradiation, and at 4, 24 h, 2 and 4 days after irradiation in the younger group; and before and immediately after irradiation, and at 24 h, 4, 7, and 14 days after irradiation in the older group. A total of 108 DNA samples were taken from the epidermis of 108 biopsied specimens. These samples were immunoblotted using TDM-2 and the intensities of the immunoprecipitates were measured by photodensitometer. Our results show that the CPDs had been removed from the epidermis at 4 days after irradiation at either dose in the younger group, and between 7-14 days after irradiation in the aged group. The results of our immunohistochemical studies were consistent with those of our immunoblotting studies, and indicated that basal cells repair CPDs more quickly than prickle cells in the epidermis except the amounts at 24 h after UVB irradiation, and that the CPDs were removed by epidermal turnover after the nucleotide excision repair (NER). Our results showed age-associated decline in the NER in vivo, indicating high risk of UV-associated skin cancer.


Concussion Office Based Rehabilitation Assessment: A Novel Clinical Tool for Concussion Assessment and Management.
The Concussion Office Based Rehabilitation Assessment (COBRA) is a novel tool constructed to ensure a comprehensive assessment of patients who may have sustained a concussion. The SCAT-5 (Sport Concussion Assessment Tool) has long been the gold standard for concussion assessment, however, it was designed as a sideline tool and its utility can be seen to decrease after a few days post-concussion. It also does not prompt evaluation of all the phenotypes of concussion. As such, the COBRA was created to assess the majority of potential manifestations of concussion in the office setting a day or two after an injury has been sustained. The COBRA utilizes the eight phenotypes of concussion as a guide to assess each of the potential biopsychosocial features that can be associated with these injuries and can be used to guide evidence-based treatments. Through early identification of concussion phenotypes, the clinician may start optimal treatment and hopefully prevent prolonged recovery and persisting symptoms.


Thymic dendritic cells and B cells: isolation and function.
The thymus is the primary organ in which T cells undergo rearrangement of T cell receptor alpha and beta genes, positive selection for affinity to self MHC products, and elimination (negative selection) of reactivity to self antigens. These events require an interaction of the developing T cell with other cell types in the thymus. The latter include epithelial cells, macrophages, dendritic cells, and the recently described thymic B cells the majority of which are CD5+. Here we review the identification and isolation of thymic dendritic cells and CD5+ B cells. We consider phenotype, ontogeny, and function, including possible contributions to the induction of self tolerance. Thymic dendritic cells are similar to spleen dendritic cells, but are larger and exhibit a few differences in phenotype. Dendritic cells from both organs are equally potent accessory cells for the MLR and lectin-induced, T cell proliferation. Thymic dendritic cells have higher levels of Fc receptors and support anti-CD3 dependent mitogenesis. Thymic CD5+ B cells share phenotypic features with peritoneal CD5+ B cells. However thymic B cells neither proliferate nor form antibody producing cells in response to the stimulation with LPS or anti-IgM plus IL-4, but do respond to stimulation with MHC class II-restricted helper T cells. Thymic dendritic cells and CD5+ B cells both appear at a similar time in ontogeny, about 14 d of gestation, which is the time T cell differentiation begins to take place. Dendritic cells from spleen, which are potent activators for peripheral T cells, are also potent inactivators for thymic-derived cytotoxic T cells. A correlation between reactivity to MIs products and the expression of TCR-V beta genes is well documented, and B cells are the primary APC for this antigen. Therefore, thymic CD5+ B cells may be a good tool for the investigation of tolerance to M1s products.


To the next decade and beyond.
Sebastian Ocklenburg and colleagues have written an important and exciting summary of where laterality research might go. Perhaps reiterating some of their points, it seems important to understand the nuances of laterality. Laterality research can fall into the trap of "dichotomania" - where all laterality is seen in terms of left versus right. However, important insights can also be gained by examining the strength of laterality as well as the cooperation and competition between the hemispheres. Care also needs to be taken when examining individual differences between left- and right-handers. Studies, which may suffer from type 1 errors, often stigmatise left-handers with a host of negative traits. Pre-registration and the reporting of effect size may eliminate this bias.


Synthesis and biological evaluation of a novel class of rofecoxib analogues as dual inhibitors of cyclooxygenases (COXs) and lipoxygenases (LOXs).
A group of 4-(4-methanesulfonylphenyl)-3-phenyl-2(5H)furanones possessing an acetyl, 3-oxobut-1-ynyl, [hydroxyl(or alkoxy)imino]alkyl, [hydroxyl(or alkoxy)imino]alkynyl, and N-alkoxy(or N-phenoxy)carbonyl-N-hydroxy-N-ethylamino substituents at the para-position of the C-3 phenyl ring of rofecoxib were synthesized. This group of compounds was designed for evaluation as dual inhibitors of cyclooxygenases (COXs) and lipoxygenases (LOXs) that exhibit in vivo anti-inflammatory and analgesic activities. In vitro COX-1/COX-2, and 5-LOX/15-LOX, isozyme inhibition structure-activity relationships identified 3-[4-(1-hydroxyimino)ethylphenyl]-4-(4-methanesulfonylphenyl)-2(5H)furanone (17a) having an optimal combination of COX-2 (COX-2 IC50 = 1.4 microM; COX-2 SI > 71), and 5-LOX and 15 LOX (5-LOX IC50 = 0.28 microM; 15-LOX IC50 = 0.32 microM), inhibitory effects. It was also discovered that 3-[4-(3-hydroxyiminobut-1-ynyl)phenyl]-4-(4-methanesulfonylphenyl)-2(5H)furanone (18a) possesses dual COX-2 (IC50 = 2.7 microM) and 5-LOX (IC50 = 0.30 microM) inhibitor actions. Further in vivo studies employing a rat carrageenan-induced paw edema model showed that the oxime compounds (17a, 18a) were more potent anti-inflammatory agents than the 5-LOX inhibitor caffeic acid, and 15-LOX inhibitor nordihydroguaiaretic acid (NDGA), but less potent than the selective COX-2 inhibitor celecoxib. The results of this investigation showed that incorporation of a para-oxime moiety on the C-3 phenyl ring of rofecoxib provides a suitable template for the design of dual inhibitors of the COX and LOX enzymes.


Verbal-spatial and visuospatial coding of number-space interactions.
A tight correspondence has been postulated between the representations of number and space. The spatial numerical association of response codes (SNARC) effect, which reflects the observation that people respond faster with the left-hand side to small numbers and with the right-hand side to large numbers, is regarded as strong evidence for this correspondence. The dominant explanation of the SNARC effect is that it results from visuospatial coding of magnitude (e.g., the mental number line hypothesis). In a series of experiments, we demonstrated that this is only part of the story and that verbal-spatial coding influences processes and representations that have been believed to be purely visuospatial. Additionally, when both accounts were directly contrasted, verbal-spatial coding was observed in absence of visuospatial coding. Relations to other number-space interactions and implications for other tasks are discussed.


A case-control study on the dietary taurine intake, nutrient status and life stress of functional constipation patients in Korean male college students.
Constipation is a common gastrointestinal symptom in Korea as well as in Western countries. This study was performed to investigate the dietary taurine intake, nutrient status, and life stress of functional constipation (FC) patients in Korean male college students. Research data were collected in 2008 and a total of 104 male students (52 with FC patients and 52 healthy controls without FC) were included. FC patients were defined by the codes for the Rome Modular Questionnaire and healthy controls without FC were matched for age, height, weight and BMI. A self-administered life stress score and 3-day recall method were used to assess life stress level and dietary intake, respectively. The averages of age, height, weight, body fat percentage and body mass index (BMI) of male students were 23.4 years, 174.1 cm, 71.9 kg, 19.0 % and 23.7 kg/m2, respectively. Average intake of dietary taurine was 126.8 mg/day in FC patients and 105.1 mg/day in control group. The average intake of total calorie (p<0.05), plant protein (p<0.01), plant fat (p<0.001), carbohydrate (p<0.05), plant calcium (p<0.05) of FC patients were significantly higher compared to control group. The average total life stress score (p<0.01), economy problem score (p<0.05), future problem score (p<0.05) and value problem score (p<0.05) of FC patients were significantly higher compared to control group. These results may suggest that FC patients show a higher life stress score and intake of some nutrient such as total calorie, plant protein, plant fat, carbohydrate and plant calcium in Korean male college students. Therefore, a further large-scale study is needed about correlation between life stress and nutrients intake including dietary taurine.


Sex differences in binge eating patterns in male and female adult rats.
Several efforts are underway to model binge eating in animals in order to advance neurobiological models of risk. However, knowledge of sex differences in these models is currently lacking. The goal of the present study was to examine sex differences in binge eating phenotypes using a well-established rodent model (i.e., the binge eating resistant/binge eating prone model). Thirty male and 30 female adult Sprague-Dawley rats were exposed to feeding tests consisting of intermittent access to palatable food (PF). Rats were then categorized as binge eating prone (BEP) based on the amount and consistency of PF consumption across tests. Across multiple methods for BEP classification, rates of BEP phenotypes were two to six times higher in female than male rats. Findings provide support for sex differences in rodent models of binge eating and highlight the promise of the BER/BEP model for understanding neurobiological mechanisms underlying sex differences in risk.


Hepatitis C positive organ transplantation to negative recipients at a multiorgan Canadian transplant centre: ready for prime time.
Transplantation offers the best survival for patients with end stage organ disease. Transplant of hepatitis C virus (HCV) nucleic acid test (NAT) positive organs into negative recipients is a novel strategy that can expand the donor pool. We aim to evaluate our centre's experience. We preformed a retrospective review of anti-HCV NAT positive and negative organs into negative recipients transplanted over 27 months. Primary outcome was the success rate of eradication of HCV post-transplant. Secondary outcomes were rate of transmission of HCV, treatment adverse events, and graft failure. 33 anti-HCV positive organs were transplanted into negative recipients. 22 (66.7%) were NAT positive. Median recipients age was 49 years (interquartile range [IQR] 44.5-62.0) with the majority being males (57.6%). NAT positive organ transplantations included 16 kidneys, 3 livers, 1 kidney-pancreas, 1 liver-kidney, and 1 heart. The most common HCV genotype was 1a (59.1%). The median time to initiating therapy was 41.5 days. SVR12 was 100% in patients who finished therapy. There were no adverse events with therapy and no graft failure. Anti-HCV NAT positive organ transplantation into negative recipients is safe with excellent eradication rates and no significant adverse events or graft failure. This would expand donor pool to close the gap between supply and demand.


Pharmacological considerations for the treatment of COVID-19 in people living with HIV (PLWH).
When coronavirus infectious disease-2019 (COVID-19) blew up, ill-fated auguries on the collision between COVID-19 and the human immunodeficiency virus (HIV) epidemics loomed. Data from observational studies suggest similar incidence attacks of SARS-CoV-2 infection in people living with HIV (PLWH) and HIV-uninfected populations. The mortality rate of COVID-19 is similar in both populations too. The authors discuss the role of combination antiretroviral therapy (cART) in preventing infection or reducing COVID-19 severity. They also discuss the pharmacological interventions for COVID-19 in PLWH. Management of COVID-19 in PLWH is no different from the general population. It should be based on careful supportive care, emphasizing lung-protective ventilation, and wise pharmacological interventions. The antiviral drug remdesivir and dexamethasone are the only pharmacological interventions with clinical benefit for COVID-19, whereas anticoagulation may prevent thrombotic complications. The experience with using these drugs in PLWH is limited, which prevents from rendering well-founded conclusions. Until more data on COVID-19 in PLWH become available, the best weapons within our reach are sound supportive care and sensible use of RDV and dexamethasone, bearing in mind the potential for drug-drug interactions of most corticosteroids and antiretroviral drugs.


Modulation of epidermal growth factor receptor activity and related responses by the 7-deazaguanine derivative, queuine.
Epidermal growth factor (EGF) induces autophosphorylation of its cognate receptor at tyrosine residues. Here we show that queuine (q), a widely distributed modified guanine analogue occurring free or as a tRNA wobble base, modulates this EGF receptor activity in vitro and in intact cells. Autophosphorylation of the immunopurified receptor from human A431 epidermoid carcinoma cells was enhanced three to fourfold in the presence of physiological concentrations of q. Using a membrane fraction of A431 cells, a twofold increase in autophosphorylation activity in the presence of q was observed, however, only when the receptor was activated by the ligand. In intact A431 cells, q enhanced the initial ligand-induced autophosphorylation of the EGF receptor three to fourfold. However, upon longer treatment of the cells with EGF in the presence of q, significantly less autophosphorylated receptor was detectable compared with stimulation of cells in the absence of q. A similar q-dependent modulation of EGF receptor autophosphorylation was observed also in human cervical carcinoma cells HeLa-S3. Treatment of q-deficient HeLa cells with EGF induced the c-fos gene expression, transiently increased the activity of the anoxic stress protein LDH k, and stimulated proliferation. Treatment of HeLa cells with EGF in the presence of q resulted in a delayed c-fos gene expression and an accelerated increase and decrease of LDH k activity. The stimulatory effect of low doses of EGF on HeLa cell proliferation was completely antagonized in the presence of q. The results suggest that the mitogenic signalling initiated by the EGF receptor is modulated by q.


The PR5K receptor protein kinase from Arabidopsis thaliana is structurally related to a family of plant defense proteins.
We have isolated an Arabidopsis thaliana gene that codes for a receptor related to antifungal pathogenesis-related (PR) proteins. The PR5K gene codes for a predicted 665-amino acid polypeptide that comprises an extracellular domain related to the PR5 proteins, a central transmembrane-spanning domain, and an intracellular protein-serine/threonine kinase. The extracellular domain of PR5K (PR5-like receptor kinase) is most highly related to acidic PR5 proteins that accumulate in the extracellular spaces of plants challenged with pathogenic microorganisms. The kinase domain of PR5K is related to a family of protein-serine/threonine kinases that are involved in the expression of self-incompatibility and disease resistance. PR5K transcripts accumulate at low levels in all tissues examined, although particularly high levels are present in roots and inflorescence stems. Treatments that induce authentic PR5 proteins had no effect on the level of PR5K transcripts, suggesting that the receptor forms part of a preexisting surveillance system. When the kinase domain of PR5K was expressed in Escherichia coli, the resulting polypeptide underwent autophosphorylation, consistent with its predicted enzyme activity. These results are consistent with PR5K encoding a functional receptor kinase. Moreover, the structural similarity between the extracellular domain of PR5K and the antimicrobial PR5- proteins suggests a possible interaction with common or related microbial targets.


Affective regulation through touch: homeostatic and allostatic mechanisms.
We focus on social touch as a paradigmatic case of the embodied, cognitive, and metacognitive processes involved in social, affective regulation. Social touch appears to contribute three interrelated but distinct functions to affective regulation. First, it regulates affects by fulfilling embodied predictions about social proximity and attachment. Second, caregiving touch, such as warming an infant, regulates affect by socially enacting homeostatic control and co-regulation of physiological states. Third, affective touch such as gentle stroking or tickling regulates affect by allostatic regulation of the salience and epistemic gain of particular experiences in given contexts and timescales. These three functions of affective touch are most likely mediated, at least partly, by different neurobiological processes, including convergent hedonic, dopaminergic and analgesic, opioidergic pathways for the attachment function, 'calming' autonomic and endocrine pathways for the homeostatic function, while the allostatic function may be mediated by oxytocin release and related 'salience' neuromodulators and circuits.


Rapidly induced gene networks following induction of long-term potentiation at perforant path synapses in vivo.
The canonical view of the maintenance of long-term potentiation (LTP), a widely accepted experimental model for memory processes, is that new gene transcription contributes to its consolidation; however, the gene networks involved are unknown. To address this issue, we have used high-density Rat 230.2 Affymetrix arrays to establish a set of genes induced 20-min post-LTP, and using Ingenuity Pathway network analysis tools we have investigated how these early responding genes are interrelated. This analysis identified LTP-induced regulatory networks in which the transcription factors (TFs) nuclear factor-KB and serum response factor, which, to date, have not been widely recognized as coordinating the early gene response, play a key role alongside the more well-known TFs cyclic AMP response element-binding protein, and early growth response 1. Analysis of gene-regulatory promoter sites and chromosomal locations of the genes within the dataset reinforced the importance of these molecules in the early gene response and predicted that the coordinated action might arise from gene clustering on particular chromosomes. We have also identified a transcription-based response that affects mitogen-activated protein kinase signaling pathways and protein synthesis during the stabilization of the LTP response. Furthermore, evidence from biological function, networks, and regulatory analyses showed convergence on genes related to development, proliferation, and neurogenesis, suggesting that these functions are regulated early following LTP induction. This raises the interesting possibility that LTP-related gene expression plays a role in both synaptic reorganization and neurogenesis.


[Construction of a retroviral vector expressing antisense N-myc gene].
In their previous studies the authors demonstrated that nerve growth factor-induced differentiation of neuroblastoma cell lines was closely related with nerve growth factor receptors and amplification of N-myc oncogenes. The authors have also successfully restored the nerve growth factor receptor expression in the cell lines which lacked expression of nerve growth factor receptors. In order to clearify the role of N-myc oncogenes during nerve growth factor-induced differentiation of neuroblastoma cell lines, a new retroviral vector was constructed to express antisense N-myc genes. This new vector contained a puromycin resistant gene, which allowed the authors to express another gene in the cell lines which had already been neomycin resistant.


Glass in the frontal sinus: 28-year delayed presentation.
Reports of delayed presentation of foreign bodies in the frontal sinus are infrequent and likely to become rarer with the widespread availability of computed tomography in the last 2 decades. We present a case in which glass from a road traffic injury was found in the frontal sinus, causing symptoms of frontal sinusitis 28 years after the initial injury. We also present a review of the literature.


NHS hospital readiness to embrace the proposed NICE guidelines on abdominal aortic aneurysm: a public perspective.
The National Institute for Health and Care Excellence published a draft consultation update on abdominal aortic aneurysm, which was expected to be published on 7 November 2018. This article analyses the readiness of NHS hospitals and their workforce to embrace the proposed guidelines. The trust and individual surgeon-level anonymised data in the public domain for elective, rupture and complex abdominal aortic aneurysm cases were collected and analysed for all the acute care trusts providing these services from the Vascular Society of Great Briton and Ireland's prospective National Vascular Registry database. Of the 95 acute care trusts providing the service for the year 2017, the annual volume of infrarenal abdominal aortic aneurysm (both endovascular and open repairs) ranged between 0 and 137. Of these, 64 (67.36%) trusts had an annual volume of fewer than 60 cases. A total of 366 (approximately 75% of 490) vascular surgeons have performed 10 or fewer open abdominal aortic aneurysm repairs in three years (2014-2016) with a mean operating volume of 1.452 procedures per surgeon per three years (n = 254, median 0, interquartile range, IQR, 0-3, 0.484 procedures per surgeon per year) and about 51% of the vascular surgeons have only performed five or fewer procedures in those three years with a mean operating volume of 3.455 per surgeon per three years (n = 367, median 3, IQR 0-3, 1.151 per surgeon per year). The observations show that most UK acute hospitals lack the optimum case volume necessary to embrace the proposed change in the guideline.


Respiratory Outcome after Preterm Birth: A Long and Difficult Journey.
Despite notable advances in the survival and management of preterm infants in recent decades, chronic lung disease remains a common complication. Approximately one in three infants born preterm (< 32 weeks of gestation) are hospitalized with respiratory problems (mainly due to infections) in their first 2 years of life, and the risk of childhood wheezing is three times higher in this population. By comparison with infants born at term, there seems to be a higher incidence of respiratory morbidity in those born preterm, even in the absence of bronchopulmonary dysplasia (BPD) and in late-preterm babies. Although long-term follow-up data are still not collected systematically, there is evidence of preterm infants' respiratory symptoms, lung function impairments, and radiological abnormalities, tending to persist throughout childhood and into early adulthood. Respiratory conditions associated with preterm birth are often diagnosed and treated as asthma, but the pathophysiological patterns of BPD and asthma are very different. Future research should focus on characterizing preterm infants' pathological pulmonary features by gestational age at birth, and presence or absence of BPD. Improving our current knowledge of the respiratory disorder associated with prematurity might hopefully prompt targeted follow-up protocols, and novel prevention strategies and treatment approaches.


The 1298A-->C polymorphism in methylenetetrahydrofolate reductase (MTHFR): in vitro expression and association with homocysteine.
A common mutation in methylenetetrahydrofolate reductase (MTHFR), 677C-->T, is associated with reduced enzyme activity, a thermolabile enzyme and mild hyperhomocysteinemia, a risk factor for vascular disease. Recently, a second common mutation (1298A-->C; glutamate to alanine) was reported, but this mutation was suggested to increase homocysteine only in individuals who carried the bp677 variant. To evaluate the functional consequences of this mutation, we performed site-directed mutagenesis and in vitro expression. For in vivo assessment of clinical impact, we examined the 1298A-->C genotypes and plasma homocysteine in 198 individuals from the NHLBI Family Heart Study that had previously been assessed for the 677 substitution. Site-directed mutagenesis of the human cDNA was performed to generate enzymes containing each of the two mutations, as well as an enzyme containing both substitutions. Enzyme activity and thermolability were assessed in bacterial extracts. The activity of the wild-type cDNA was designated as 100%; mutant enzymes containing the 1298 and 677 mutations separately had 68% (+/-5.0) and 45% (+/-10.8), respectively, of control activity while the enzyme containing both mutations had 41% (+/-12.8) of control activity. The 1298 mutation was not associated with a thermolabile enzyme. In the Family Heart Study, fasting homocysteine was significantly higher (P<0.05) in individuals heterozygous for both substitutions, compared to individuals who carried only the 677C-->T variant. This study suggests that two variants in MTHFR should be assessed as genetic risk factors for hyperhomocysteinemia.


Periventricular echodensity measured with the integrated backscatter system: from a qualitative assessment to a quantitative approach.
The degree of periventricular white matter echodensity in preterm infants has been utilized as a sign of the early ultrasonographic appearance of periventricular leukomalacia, and this has been called periventricular echodensity (PVE). The aim of this study was to quantitatively measure PVE utilizing a new method which is called calibrated integrated backscatter (calibrated IB). Eighty-eight preterm infants (extremely low birth weight infants, n = 17; very low birth weight infants, n = 26; low birth weight infants, n = 45) without any CNS abnormality were enrolled. IB is the returned sound pressure against supersonic waves sent from an ultrasonographic machine. The IB of the choroid plexus and periventricular white matter in the subrolandic area were measured on a parasagittal cerebral image. The degree of PVE was defined by subtracting the IB of the choroid plexus from that of the periventricular white matter in the subrolandic area (calibrated IB of PVE). The intraobserver and interobserver correlations were both excellent (between 0.87 and 0.98 as correlation coefficients). There was a trend for the calibrated IB of PVE to decrease in accordance with time after birth, with a significant difference in very low birth weight and low birth weight infants. The objectively measured brightness of PVE was comparable to that of the choroid plexus irrespective of the size of the infants. Measurement of the calibrated IB of PVE might be a reliable method to assess PVE.


Lucky Switcheroo: Dramatic Potency and Selectivity Improvement of Imidazoline Inhibitors of Human Carbonic Anhydrase VII.
A substantial improvement of potency and selectivity of imidazoline-based inhibitors of hCA VII (a promising target for the treatment of seizures and neuropathic pain) was achieved by simply switching the position of the benzenesulfonamide moiety from N1 (as in the earlier reported series) to C2. Selectivity indices vs the off-target isoforms (hCA I, I, I and IV) greater than 100 were reached, which is exceedingly rare for hCA VII inhibitors. The drastic profile improvement of the new series has been rationalized by an additional hydrogen bonding with the nonconserved Q69 residue in the active site of hCA VII (absent in the other three isoforms studied), which also results in a favorable accommodation of the inhibitor's lipophilic periphery in the nearby hydrophobic pocket. The robustness of the docking simulations was tested and confirmed by molecular dynamics simulations.


Feasibility, Safety, and Long-Term Outcomes of Zero-Contrast Percutaneous Coronary Intervention in Patients With Chronic Kidney Disease.
The long-term safety and utility of intravascular ultrasound (IVUS)-guided zero-contrast percutaneous coronary intervention (PCI) in patients with chronic kidney disease (CKD) are unknown.Methods and Results: A total of 698 consecutive patients treated with PCI (1,061 procedures) in our center were studied. Patients with acute coronary syndrome, who are on maintenance hemodialysis, and who had a planned rotational atherectomy were excluded. Finally, they were divided into 2 groups: zero-contrast PCI (n=55, 78 procedures) and conventional PCI (n=462, 670 procedures). After propensity score matching, 50 patients were matched for each group to evaluate long-term outcomes. Primary endpoints were major adverse cardiovascular events (MACE), including all-cause death, non-fatal myocardial infarction (MI), and clinically driven target lesion revascularization. All patients in the zero-contrast PCI group had stage 3-5 CKD with an estimated glomerular filtration rate of 38.3±14.8 mL/min/1.73 m2. Zero-contrast PCI was successful in all 78 procedures without renal events such as acute kidney injury or emergent hemodialysis and procedural complications such as coronary perforation or periprocedural MI. During a follow-up period of 32 months, 7 patients died (1 cardiac, 6 non-cardiovascular), and 4 patients were introduced to renal replacement therapy. The incidence of MACE was similar between the zero-contrast and conventional PCI groups (log-rank, P=0.95). IVUS-guided zero-contrast PCI might be safe and feasible in patients with CKD with satisfactory acute and long-term renal and cardiovascular outcomes.


(Fluoromethylsulfonyl)methylation of Quinoxalinones Using NaSO2CH2F for C-F Bond Cleavage.
We developed a facile, efficient, and scalable route to achieve monofluoromethylsulfinyl alkylation of quinoxalinones. NaSO2CH2F served as the source of methylene to construct new C-C and C-S bonds via C-F bond cleavage. NaSO2CH2F was also the source of SO2CH2F. Density functional theory calculations confirmed the proposed mechanism, in which the SO2CH2F radical is immediately trapped. The reaction exhibited a high level of atom economy. Moreover, some representative products displayed excellent biological activity.


Interleukin-27 Inhibits Herpes Simplex Virus Type 1 Infection by Activating STAT1 and 3, Interleukin-6, and Chemokines IP-10 and MIG.
Interleukin-27 (IL-27) inhibits the replication of many viruses, but the mechanism differs according to virus and cell type. In this study, we observed that IL-27 expression was upregulated in herpes simplex virus type 1 (HSV-1)-infected SJL/J mice, which led us to further investigate the role of IL-27 in HSV-1 infection using epithelial, glioma, and immunological cells as cell models. We showed that in all studied cell lines, the IL-27 messenger RNA (mRNA) level was upregulated due to the HSV-1 infection. When the cells were primed with IL-27 before the virus infection, the virus release was prevented, indicating an antiviral role of IL-27 in HSV-1 infection. Furthermore, we observed that IL-27 secretion to the culture medium was reduced in infected epithelial and immunological cells, but not in glioma cells. Not surprisingly, HSV-1 induced type I, II, and III interferons regardless of cell line, but IL-27 itself caused varying interferon responses dependent on cell type. However, common to all cell types was the IL-27-stimulated secretion of IL-6 and chemokines IP-10 and MIG. In addition, IL-27 stimulation activated STAT1 and STAT3 in HeLa and T98G cells, suggesting that IL-27 engages the STAT1/3 pathway, which then leads to the upregulation of IL-6, IP-10, and MIG.


Morphological, Structural, Thermal, Permeability, and Antimicrobial Activity of PBS and PBS/TPS Films Incorporated with Biomaster-Silver for Food Packaging Application.
The development of antimicrobial film for food packaging application had become the focus for researchers and scientists. This research aims to study the characteristics and antimicrobial activity of novel biofilms made of poly (butylene succinate) (PBS) and tapioca starch (TPS) added with 1.5% or 3% of Biomaster-silver (BM) particle. In morphological examination, the incorporation of 3% BM particle was considerably good in forming well-structured PBS film. Meanwhile, the functional groups analysis revealed the 3% BM particle was effectively interacted with PBS molecular chains. The flame retard behavior of BM metal particle also helped in enhancing the thermal stability for pure PBS and PBS/TPS films. The nucleating effect of BM particles had improved the films crystallinity. Small pore size features with high barrier property for gas permeability was obtained for BM filled PBS/TPS films. From antimicrobial analysis, the BM particles possessed antimicrobial activity against three bacteria Staphylococcus aureus, Escherichia coli, and Salmonella Typhimurium in which PBS/TPS 3% BM film exhibited strong antimicrobial activity against all tested bacteria, however, PBS/TPS 1.5% BM film exhibited strong antimicrobial activity against E. coli only. Hence, the incorporation of BM into PBS/TPS film could be a sustainable way for developing packaging films to preserve food products.


A comprehensive clinical analysis of the use of percutaneous endoscopic debridement for the treatment of early lumbar epidural abscesses.
The purpose of this study is to evaluate the safety and efficacy of a percutaneous endoscopic debridement and drainage for lumbar infections with early epidural abscesses. Eight cases of early epidural abscess underwent lumbar intervertebral space debridement and drainage by percutaneous endoscopic. Laboratory indicators, pathogenic microorganisms and complications were documented, and the ASIA scores were used to assess preoperative and postoperative neurological function changes. Additionally, the VAS was used to evaluate the therapeutic effect. The average duration of the drainage tube was 11.25 ± 3.96 days (7-20 days), and the epidural abscess was eliminated after the tube was taken out. Postoperative CRP (14.40 ± 12.50 mg/L) and ESR (48.37 ± 16.05 mm/1 h) were significantly lower than the preoperative CRP (62.5 ± 61.1 mg/L) and ESR (75.30 ± 26.20 mm/1 h). The VAS score after the operation (2.50 ± 0.92 points) was significantly lower than the one before the surgery (8.25 ± 0.83 points). 5 patients experienced lower extremity pain and neurological dysfunction prior to surgery, however, after drainage, the lower extremity pain dissipated and the lower extremity muscle strength improved in one patient. All 8 patients were followed up for a period of (28.13 ± 10.15) months, including 3 patients with spinal segmental instability who had lumbar bone graft and internal fixation for the second stage. At the end of the follow-up, all 8 patients were clinically cured without any progressive nerve injury, paraplegia or recurrence of infection. Percutaneous Endoscopic Debridement and Drainage is an effective way to drain intraspinal abscesses, thus avoiding any potential progressive harm to the spinal cord.


Swedish forensic nursing care: nurses' professional contributions and educational needs.
Nurses (registered nurses, RN, and licensed mental nurses, LMN) working in five Swedish forensic psychiatric units filled in a questionnaire designed for general psychiatric nursing, but modified for forensic use. In this report, data regarding how nursing care could contribute to improved care and the organizational changes needed and what knowledge the nurses need, in order to be able to meet the demands in the future, were analysed by means of content analysis. The salient findings were: (i) an interpersonal patient-nurse relationship based on trust, empathy, respect and responsibility for the patients' personal resources and knowledge seems to be the essence of nursing care and a way to improve care; and (ii) the nurses' educational needs emanate from different treatment modalities, how to perform different treatments, how to establish developing relationships and in-service training adapted to the ward-specific problems.


[Endogenous cannabinoid system. Effect on neuronal plasticity and pain memory].
The aim of this study was to evaluate the role of the endogenous cannabinoid system in controlling neuroplasticity. The pain threshold for electrical stimuli was determined in transgenic mice lacking the cannabinoid receptor type 1 (CB1(-/-)) and in the corresponding respective wild-type animals. Electrophysiological experiments were performed in prepared brain slices to test the effect of endogenous and exogenous cannabinoids on synaptic transmission and long-term potentiation (LTP) in the amygdala. The pain threshold was nearly identical in both groups for the first pain induction; however, with repeated pain induction it decreased to a significantly greater extent in the CB1(-/-) mice than in the wild-type animals. Synoptic transmission and the inducibility of LTP were not influenced by the acute pharmacological blockade of CB1 receptors, but inhibited by the CB1 agonist WIN55,212-2. The endogenous cannabinoid system is involved in the control of neuroplasticity as part of pain processing . Cannabinoids prevent the formation of LTP in the amygdala via activation of CB1 receptors. Synoptic transmission and the inducibility of LTP were not influenced by the acute pharmacological blockade of CB1 receptors, but inhibited by the CB1 agonist Win55,212-2.


Can mobile units improve the strategies for cervical cancer prevention?
Cervical cancer is a serious public health problem in women in developing countries because of absence or ineffectiveness of screening programs. Several biases to access medical care and inequity of public health system in a continental country like Brazil limit the implementation of adequate programs to appropriately prevent the cervical cancer. Therefore, the aim of this study was to evaluate the results of applying the mobile unit (MU) for cervical cancer screening. From May 2003 to May 2004, a cervical cancer screening was offered to women aged 20-69 years, residing in 19 municipal districts of the Barretos county region, in São Paulo. Out of the 9,560 examination available, 2,964 (31%) women underwent screening. The medium distance traveled by the MU was 45 km. The medium time spent by women in the MU for completion of the questionnaire and doing the exam was 20 minutes. It was observed that 17.0% of women screened had never had the test or had not had it repeated within the last 3 years. The negative response was more common among women aged 20 to 29 years and 60 to 69 years and among women with less schooling and lower socio-economic income (P < 0.05). MU can significantly overcome the chronic deficiency of public health system accessibility offering opportunity to these women to participate in screening programs.


Coexpression, purification and characterization of the E and S subunits of coenzyme B(12) and B(6) dependent Clostridium sticklandii D-ornithine aminomutase in Escherichia coli.
D-Ornithine aminomutase from Clostridium sticklandii comprises two strongly associating subunits, OraS and OraE, with molecular masses of 12,800 and 82,900 Da. Previous studies have shown that in Escherichia coli the recombinant OraS protein is synthesized in the soluble form and OraE as inclusion bodies. Refolding experiments also indicate that the interactions between OraS and OraE and the binding of either pyridoxal phosphate (PLP) or adenosylcobalamin (AdoCbl) play important roles in the refolding process. In this study, the DNA fragment containing both genes was cloned into the same expression vector and coexpression of the oraE and oraS genes was carried out in E. coli. The solubility of the coexpressed OraS and OraE increases with decreasing isopropyl thio-beta-D-galactoside induction temperature. Among substrate analogues tested, only 2,4-diamino-n-butyric acid displays competitive inhibition of the enzyme with a K(i) of 96 +/- 14 microm. Lys629 is responsible for the binding of PLP. The apparent K(d) for coenzyme B(6) binding to d-ornithine aminomutase is 224 +/- 41 nm as measured by equilibrium dialysis. The mutant protein, OraSE-K629M, is successfully expressed. It is catalytically inactive and unable to bind PLP. Because no coenzyme is involved in protein folding during in vivo translation of OraSE-K629M in E. coli, in vitro refolding of the enzyme employs a different folding mechanism. In both cases, the association of the S and E subunit is important for D-ornithine aminomutase to maintain an active conformation.


Do DNA sequence variants in ABCA1 contribute to HDL cholesterol levels in the general population?
HDL has a key role in reverse cholesterol transport, mobilizing cholesterol from the peripheral tissues to liver. In this process, the ABC transporter A1 (ABCA1) protein controls the efflux of intracellular cholesterol to apoAI, the major apolipoprotein of HDL. Since ABCA1 mutations were discovered to cause Tangier disease, a rare recessive HDL deficiency, it has been speculated that sequence variants in ABCA1 might also contribute to variations in plasma HDL cholesterol levels in the general population. A new study provides genetic evidence supporting this hypothesis.