Differential recruitment of opportunistic taxa leads to contrasting abilities in carbon processing by bathypelagic and surface microbial communities.
Different factors affect the way dissolved organic matter (DOM) is processed in the ocean water column, including environmental conditions and the functional capabilities of the communities. Recent studies have shown that bathypelagic prokaryotes are metabolically flexible, but whether this versatility translates into a higher ability to process DOM has been barely explored. Here we performed a multifactorial transplant experiment to compare the growth, activity and changes in DOM quality in surface and bathypelagic waters inoculated with either surface or bathypelagic prokaryotic communities. The effect of nutrient additions to surface waters was also explored. Despite no differences in the cell abundance of surface and deep ocean prokaryotes were observed in any of the treatments, in surface waters with nutrients the heterotrophic production of surface prokaryotes rapidly decreased. Conversely, bathypelagic communities displayed a sustained production throughout the experiment. Incubations with surface prokaryotes always led to a significant accumulation of recalcitrant compounds, which did not occur with bathypelagic prokaryotes, suggesting they have a higher ability to process DOM. These contrasting abilities could be explained by the recruitment of a comparatively larger number of opportunistic taxa within the bathypelagic assemblages, which likely resulted in a broader community capability of substrate utilization.


Asprosin, a Fasting-Induced Glucogenic Protein Hormone.
Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin. Asprosin is secreted by white adipose, circulates at nanomolar levels, and is recruited to the liver, where it activates the G protein-cAMP-PKA pathway, resulting in rapid glucose release into the circulation. Humans and mice with insulin resistance show pathologically elevated plasma asprosin, and its loss of function via immunologic or genetic means has a profound glucose- and insulin-lowering effect secondary to reduced hepatic glucose release. Asprosin represents a glucogenic protein hormone, and therapeutically targeting it may be beneficial in type II diabetes and metabolic syndrome.


Unilateral multicystic dysplastic kidney: single-center experience.
Multicystic dysplastic kidney (MCDK) is one of the most common renal abnormalities in children. The aim of our study was to evaluate the clinical course and outcome of patients with MCDK. Ninety pediatric patients with unilateral MCDK followed by the Pediatric Nephrology Department of Bakirkoy Maternity and Children's Hospital between 1990 and 2007 were included in this retrospective study. The dimercaptosuccinic acid radionuclide scan revealed no function in MCDK in all of our patients. Voiding cystourethrogram was performed in all patients. Twenty patients (22.2%) had abnormalities in the contralateral kidney. Nephrectomy was performed in 41 patients (45.5%). Twelve patients had undergone routine nephrectomy before 1996. Since then, patients have been followed up conservatively, and nephrectomy has been performed only when indicated. Indication of nephrectomy was arterial hypertension in 16 patients (23.1%), recurrent urinary tract infection (UTI) in 11 (15.9%), and severe abdominal pain in two (2.8%). Hypertension was noted within the first year of life in all patients except two. MCDK completely involuted in 39.3% within 48 months. There was no malignant transformation, proteinuria, or renal failure. In conclusion, hypertension is often noticed in infants with MCDK. Uninephrectomy leads to normalization. However, prospective studies are needed to exclude a spontaneous improvement of hypertension.


Spontaneous transformation of cynomolgus mesenchymal stem cells in vitro: further confirmation by short tandem repeat analysis.
It remains a highly debatable issue whether mesenchymal stem cells (MSCs) can undergo spontaneous transformation in culture. Recently, two groups retracted their previous publications due to the finding that the claimed transformed cells are actually contaminating cancer cells, which calls for a more stringent identification of transformed cells in the field. In this study, we continued with our previous finding of spontaneous transformation of cynomolgus MSCs and provided further evidence using short tandem repeat analysis that the transformed mesenchymal stem cells were indeed derived from cynomolgus MSCs.


Detecting computer-enhanced dentistry.
Recent developments in digital imaging in dentistry and easy-to-use editing software present many occasions for altering or fraudulently changing digital images of products, patients, their dental conditions, treatments, and radiographs. Though seemingly impossible to detect when carefully done, there are numerous clues of digital editing that can be detected by the alert practitioner.


Development and Characterization of Activated Carbon from Olive Pomace: Experimental Design, Kinetic and Equilibrium Studies in Nimesulide Adsorption.
The lack of adequate treatment for the removal of pollutants from domestic, hospital and industrial effluents has caused great environmental concern. Therefore, there is a need to develop materials that have the capacity to treat these effluents. This work aims to develop and characterize an activated charcoal from olive pomace, which is an agro-industrial residue, for adsorption of Nimesulide in liquid effluent and to evaluate the adsorption kinetics and equilibrium using experimental design. The raw material was oven dried at 105 °C for 24 h, ground, chemically activated in a ratio of 1:0.8:0.2 of olive pomace, zinc chloride and calcium hydroxide and thermally activated by pyrolysis in a reactor of stainless steel at 550 °C for 30 min. The activated carbon was characterized by Fourier Transform Infrared (FTIR) spectroscopy, X-ray Diffractometry (XRD), Brunauer, Emmett and Teller (BET) method, Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM), density and zero charge potential analysis. The surface area obtained was 650.9 m2 g-1. The kinetic and isothermal mathematical models that best described the adsorption were PSO and Freundlich and the highest adsorption capacity obtained was 353.27 mg g-1. The results obtained showed the good performance of activated carbon produced from olive pomace as an adsorbent material and demonstrated great potential for removing emerging contaminants such as Nimesulide.


On-line Fourier transform infrared spectrometric detection in gradient capillary liquid chromatography using nanoliter-flow cells.
A capillary liquid chromatographic system has been successfully interfaced with a mid-IR Fourier transform infrared (FT-IR) spectrometer. Spectra were recorded on-line using a micromachined transmission CaF(2) cell (internal volume of 7.5 nL) that was placed on a dedicated beam condenser attached to the spectrometer. Linear gradients were run from (50:50) to (35:65) water (0.05% TFA)/acetonitrile in 15 min for the separation of standard solutions of four nitrophenols (4-nitrophenol, 3-methyl-4-nitrophenol, 2,4-dinitrophenol, and 2-nitrophenol) in a reversed phase system, providing limits of detection between 35 and 94 ng on-column. The changing background absorption due to gradient elution was successfully corrected by using a dedicated algorithm implemented in Matlab. When this chemometric data treatment was used, highly characteristic analyte spectra could be recorded as indicated by correlation coefficients between 89 and 95.8%, obtained when comparing mid-IR spectra of standard solutions and the spectra extracted from the chromatogram.


High-dose chemotherapy and autologous hematopoietic progenitor cell rescue in children with recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors: the impact of prior radiotherapy on outcome.
The role of myeloablative chemotherapy in children with recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors (MB/ST-PNET) is controversial, in particular in patients who develop recurrent disease after craniospinal radiotherapy. In this retrospective analysis, the authors investigated the outcome of children with recurrent MB/ST-PNET who were referred for myeloablative chemotherapy and autologous hematopoietic progenitor cell rescue at Childrens Hospital Los Angeles. Thirty-three children were referred for myeloablative chemotherapy: Fourteen of those children were never transplanted because of pre-transplant adverse events, and 19, including 6 without and 13 with previous irradiation, underwent transplant. Conditioning regimens included a backbone of thiotepa, which was given either in a single cycle or in multiple sequential cycles. The 3-year post-transplant event-free survival rate in unirradiated versus previously irradiated children was 83% +/- 15% versus 20% +/- 12%, respectively (P = .04). One child who had never been exposed to radiotherapy died of toxicity; the other children received post-transplant radiotherapy and remained disease free. Nine previously irradiated children experienced 4 toxic deaths and 6 tumor recurrences (1 patient had both): An interval of <1 year between initial radiotherapy and myeloablative chemotherapy predicted a greater risk of toxic death (P = .02), whereas a history of meningeal metastases at diagnosis and a poor response to the initial rescue therapy predicted a greater risk of post-transplant recurrence (P = .03 and P = .08, respectively). Myeloablative doses of thiotepa-based chemotherapy and radiotherapy were able to cure most children who had radiotherapy-naive, chemoresponsive recurrences. Children who developed recurrences after craniospinal radiotherapy had poorer outcomes; however, cure was possible in those who had good prognostic features at presentation, chemoresponsive recurrences, and a long interval between initial radiotherapy and myeloablative chemotherapy.


Evidence for extracellular, but not intracellular, generation of angiotensin II in the rat adrenal zona glomerulosa.
Based on the observation that high levels of renin and angiotensin II (Ang II) are found in the adrenal zona glomerulosa (ZG), it has been postulated that Ang II is formed intracellularly by the renin-converting enzyme cascade in this tissue. To test this hypothesis, we examined renin-angiotensin system components in subcellular fractions of the rat adrenal ZG. Renin activity and immunoreactive-Ang II (IR-Ang II) were observed in vesicular fractions but were not colocalized. In addition, angiotensinogen, angiotensin I, and converting enzyme were not observed in the renin or IR-Ang II-containing vesicular fractions. These data do not support the hypothesis that Ang II is formed intracellularly within the renin-containing vesicles of the ZG. Rather, since modulatable renin release from adrenal ZG slices was observed and renin activity was found in dense vesicular fractions (33-39% sucrose), it is likely that Ang II formation in the ZG is extracellular and initiated by the release of vesicular renin. Receptor-mediated endocytosis and subsequent degradation of Ang II in ZG lysosomes have been shown by others. The presence of IR-Ang II in light vesicular fractions (15% sucrose) and the finding of a high correlation between ZG IR-Ang II and Ang II receptor levels suggest that the primary occurrence of this peptide in the ZG is by receptor-mediated endocytosis. In ZG lysosomal fractions 125I-labeled Ang II was degraded to 125I-labeled des-[Phe8]Ang II. Since Ang II antibodies do not recognize des-[Phe8]Ang II, these findings explain why IR-Ang II in the ZG is due predominantly to Ang II and not to its C-terminal immunoreactive fragments.


Circulating secreted frizzled-related protein 5 (Sfrp5) and wingless-type MMTV integration site family member 5a (Wnt5a) levels in patients with type 2 diabetes mellitus.
Secreted frizzled-related protein 5 (Sfrp5), an endogenous inhibitor of wingless-type MMTV integration site family (Wnt) signalling, is an anti-inflammatory adipokine whose expression is perturbed in models of obesity and type 2 diabetes mellitus (T2DM). Wnt member 5a (Wnt5a) is a representative ligand, and recent reports suggest that Wnt5a is involved in inflammatory diseases and metabolic disorders. The aim of this study was to investigate whether plasma Wnt5a and Sfrp5 levels are altered in patients with T2DM. Plasma Sfrp5 and Wnt5a concentrations were measured through enzyme-linked immunosorbent assay in type 2 diabetic and nondiabetic subjects. A total of 82 patients with T2DM and 42 nondiabetic subjects were studied. Plasma Sfrp5 levels were found to be elevated in patients with T2DM (9.4 ± 9.0 vs 7.4 ± 10.9 ng/mL, p = 0.006). In contrast, Wnt5a levels were decreased (6.8 ± 12.6 vs 9.1 ± 4.0 ng/dL, p < 0.001). Increasing concentrations of Sfrp5 were independently and significantly associated with T2DM. Multiple logistic regression analysis revealed Sfrp5 as an independent association factor for T2DM, even after full adjustment of known biomarkers. In a multiple linear regression analysis, only the fasting glucose level was positively associated with the plasma Sfrp5 level. Our results indicate that Sfrp5 may play a role in the pathogenesis of T2DM.


Increased expression of MNK1b, the spliced isoform of MNK1, predicts poor prognosis and is associated with triple-negative breast cancer.
MAP kinase interacting kinases (MNKs) modulate the function of oncogene eukaryotic initiation factor 4E (eIF4E) through phosphorylation, which is necessary for oncogenic transformation. MNK1 gives rise to two mRNAs and thus two MNK1 isoforms, named MNK1a and MNK1b. MNK1b, the splice variant of human MNK1a, is constitutively active and independent of upstream MAP kinases. In this study, we have analyzed the expression of both MNK1 isoforms in 69 breast tumor samples and its association with clinicopathologic/prognostic characteristics of breast cancer. MNK1a and MNK1b expression was significantly increased in tumors relative to the corresponding adjacent normal tissue (p < 0.001). In addition, MNK1b overexpression was found in most of the triple-negative tumors and was associated with a shorter overall and disease-free survival time. Overexpression of MNK1b in MDA-MB-231 cells induced an increase in the expression of the MCL1 antiapoptotic protein and promoted proliferation, invasion and colony formation. In conclusion, a high expression level of MNK1b protein could be used as a marker of poor prognosis in breast cancer patients and it could be a therapeutic target in triple-negative tumors.


Amyotrophic lateral sclerosis mimic syndromes: a population-based study.
The Irish ALS Register is a population-based register of the epidemiological characteristics of amyotrophic lateral sclerosis (ALS) in the republic of Ireland. To describe the clinical and demographic details of those patients included in the Irish ALS Register who were incorrectly diagnosed as having ALS (patients who were ultimately rediagnosed as having an "ALS mimic syndrome"). The medical records of each patient referred to the register are routinely reviewed and, where possible, patients are examined by our group during their illness. Between January 1, 1993, and December 31, 1997, 32 patients (representing 7.3% of 437 referrals) were rediagnosed as having a condition other than ALS. The median age at onset for these 32 patients was 56.0 years (range, 19.5-85.8 years) for men and 53.5 years (range, 39.5-70.4 years) for women. Twenty-nine patients (91%) presented with symptoms referable to the limbs, and the remainder presented with symptoms involving the bulbar musculature. Multifocal motor neuropathy was the most common condition mistaken for ALS, accounting for 7 cases (22%), followed closely by Kennedy disease (4 cases [13%]). Factors leading to diagnostic revision included evolution of atypical symptoms, results of specific investigations, and failure of symptoms to progress. Twenty-seven (84%) of the patients with an ALS mimic syndrome fulfilled the El Escorial criteria for either "suspected" or "possible" ALS, 4 (13%) met the criteria for probable ALS, and 1 (3%) had definite ALS. The application of the El Escorial diagnostic criteria may facilitate early recognition of non-ALS cases. Misdiagnosis of ALS remains a common clinical problem despite the increased availability of investigations and a greater awareness among neurologists of potential diagnostic pitfalls.


Recent progress in olefin polymerization catalyzed by transition metal complexes: new catalysts and new reactions.
A number of transition metal catalysts including early and late transition metals have been investigated for olefin polymerization and copolymerization. Progress of the field in this decade is reviewed, and important topics among them such as binary catalysts and polymerization of new monomers are described in detail. Our recent results on the polymerization of olefins having cycloalkenes and non-conjugated dienes using late transition metal complexes are also mentioned.


Paradoxical effects of kappa-opioid stimulation on the locomotor activity and Fos immunoreactivity of the preweanling rat: role of dopamine receptors.
The kappa-opioid agonist U-50,488 increases the locomotor activity of preweanling rats. The authors attempted to determine whether this effect was modulated by dopamine (DA) system functioning. Surprisingly, U-50,488's locomotor activating effects were attenuated by both the DA receptor antagonist flupenthixol and the DA receptor agonist R(-)-propylnorapomorphine (NPA). In order to determine those brain areas stimulated by U-50,488, Fos immunoreactivity was assessed in 17- and 80-day-old rats. U-50,488 not only enhanced the locomotor activity of the younger rats, but it also enhanced Fos expression in various brain areas, including the nucleus accumbens and medial striatum. NPA blocked U-50,488-induced Fos expression in the latter region. When considered together, these results indicate that U-50,488 does not increase locomotion by stimulating a DA mechanism. Instead, either agonizing or antagonizing DA receptors is sufficient to disrupt U-50,488's locomotor activating effects in the preweanling rat.


Computational Insights into Malononitrile-Based Carbanions for CO2 Capture.
Although anionic N and O sites have been widely used in chemisorption of CO2, carbanions are much less explored for CO2 capture. Here we employ ab initio calculations and quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations to examine the interaction between CO2 and the malononitrile carbanion, [CH(CN)2]-. We have explored the potential energy surface of CO2 binding by scanning the C-C distance between CO2 and the central C site of the carbanion. We find that CO2 prefers to bind to the nitrile group physically rather than to form a C-C bond via the carboxylation reaction at the sp2 C site. Moreover, the two -CN groups can attract two CO2 molecules at equal strength. The presence of an alkali metal ion enhances both physical and chemical interactions of CO2 with the malononitrile carbanion. QM/MM MD simulations further confirm the preference of physical interaction in the condensed ionic liquid phase with a phosphonium cation. Our findings suggest that ionic liquids based on the malononitrile carbanion may have a high CO2 solubility for carbon capture.


Development of Tizanidine HCl-Meloxicam loaded mucoadhesive buccal films: In-vitro and in-vivo evaluation.
The purpose of the study was to develop Tizanidine HCl (TZN) and Meloxicam (MLX) loaded bilayer mucoadhesive films intended for buccal administration, aiming to enhance the bioavailability. Bilayer films were prepared by solvent evaporation technique selecting arabinoxylan (ARX) as a sustained release (SR) layer forming polymer and hydroxypropyl methylcellulose (HPMC) E-15 as an immediate release (IR) layer-forming polymer. Prepared films were subjected to in-vitro drug release, surface morphology, mechanical strength, compatibility of the ingredients, drug contents, ex-vivo mucoadhesion strength and drug permeation. Crossover study design was applied to study the in-vivo pharmacokinetics by using albino rabbits. Various pharmacokinetic parameters including AUC, Cmax, tmax and t1/2 of both drugs loaded in films were compared with standard solution/dispersion administered to the rabbits at the dose of 1mg/kg. The results unveiled instant release and permeation of MLX from IR layer, while good controlled release and permeation characteristics of TZN from SR films over 8 h. films were of uniform thickness with smooth surface and satisfactory mechanical strength. Mucoadhesion strength was sufficient to provide suitable contact time with mucosal membrane. The pharmacokinetic study exhibited prompt absorption of MLX with better AUC 0-t (6655.64 ng/ml*h vs 6538.99 ng/ml*h) and Cmax (436.98 ng/ml vs 411.33 ng/ml) from oral dispersion. Similarly buccal films has shown enhanced half-life (9.91hr vs 2.51 hr), AUC 0-t (1043.4 ng/ml*h vs 149.1 ng/ml*h) and Cmax (91.92 ng/ml vs 42.29 ng/ml) from oral solution. A statistical investigation disclosed a significantly improved pharmacokinetics of TZN and MLX after their absorption across buccal route following administration of buccal film (p<0.05). ARX proved expedient and bilayer buccal films as a drug delivery system ascertained the dual effect of providing instant release of one active agent and persistent release of another one with improved pharmacokinetics.


A bi-national perspective on continuing medical education.
This paper presents a review and comparison of qualitative improvements in the organization, needs assessment, educational methodology, evaluation, and research in continuing medical education (CME) in the United States and Canada. Although accreditation now establishes minimal standards for CME and reduces the chances of irresponsible programs, some organizational issues (such as commercial sponsorship) and educational issues (how to "accredit" journal reading) remain unresolved. There are many examples of excellent, innovative CME programs offered by medical schools, and specialty societies have been instrumental in upgrading CME by serving as sponsors of accreditation and special projects. There is some evidence that the national health system of Canada has influenced the organization and content of Canadian CME, and these changes may soon affect U.S. programs as well. CME research has grown, with two types of research evident: the biomedical model, which assesses the efficacy of CME interventions by quantitative methods; and a model that uses grounded, ethnographic, methods to assess physician learning and performance change. Given the improvements of the past 20 years, the criticisms that focus exclusively on the lack of ideal educational planning for all CME programs are not so much wrong as dated and perhaps irrelevant. In developing their programs, CME leaders can begin to emphasize the physician learner and the clinical and social environment in which learning occurs.


Endovascular treatment of venous sinus thrombosis: a case report and review of the literature.
Dural venous sinus thrombosis (DVST) is a pathological phenomenon resulting from vascular occlusion of the cerebral venous sinuses. The mainstay of therapy for DVST is anticoagulation but more aggressive interventional therapies must be considered when medical therapy fails. A case is presented of a patient who was diagnosed with DVST, medically treated immediately but continued to deteriorate. Invasive endovascular therapies ultimately obliterated the thrombi in her sinuses. A brief review of the literature is reported.


Skeletal muscle tissue engineering using isolated myoblasts on synthetic biodegradable polymers: preliminary studies.
Skeletal muscle is responsible for the control of voluntary movement and the maintenance of structural contours of the body. Muscle loss or deficiency is encountered in various pathological states, and attempts to correct them have been employed with limited success. The aim of the present study was to tissue engineer three-dimensional vascularized skeletal muscle using isolated myoblasts attached to synthetic biodegradable polymer for tissue replacement in the enhancement of muscle regeneration. Myoblasts derived from neonatal rats (3-5-day-old), Fisher CDF-F344, were seeded onto polyglycolic acid meshes and implanted into the omentum of syngeneic adult Fisher CDF-F344 rats. Rats were sacrificed on day 30 and day 45 after the transplantation, and the cell-polymer constructs were harvested for morphological analysis. Histological analysis of the constructs were performed by hematoxylin and eosin, and immunohistochemical staining was positive for alpha sarcomeric actin and desmin skeletal muscle marker. Viable myoblasts organized between strands of degrading polymer mesh formed the new tissue, and vascularization of the entire construct was observed. Organization of neomuscle strands surrounded by vascularized tissue composed of degrading polymer and fusing myoblasts demonstrated the ability of myoblast constructs to survive, reorganize and regenerate tissue-like structures. Since myoblast transplantation to date has been limited to the cellular level of replacement, myoblast-polyglycolic acid constructs may be useful in defining the application of tissue engineering for future skeletal muscle transplantations.


Raman spectroscopy of the mixtures (x)1-butyl-1-methylpyrrolidinium chloride-(1 - x)TaCl5 in solid and molten states.
A series of novel ionic liquids consisting of 1-butyl-1-methylpyrrolidinium chloride (Pyr14Cl) and TaCl5 were obtained in a wide range of molar compositions for electrochemical application. Raman spectroscopy was used to investigate the complex formation of tantalum(V) in the mixtures of (x)Pyr14Cl-(1 - x)TaCl5 (x = 0.80-0.30) over the temperature range 20-160 degrees C. Depending on the molar composition, different species of tantalum (V) were identified. In the basic and neutral mixtures of (x)Pyr14Cl-(1 - x)TaCl5 (x = 0.80-0.50), tantalum(V) exists in the form of octahedral [TaCl6](-) in both solid and molten states. In acidic ionic liquids (x = 0.45-0.30), [Ta2Cl10] units are the main species of tantalum(V) identified in the solid state. As the temperature rose, the gradual degradation of [Ta2Cl10] units was observed in the solid state, accompanied by the formation of [TaCl6](-) and [Ta2Cl11](-) anions. In the molten state, in the range between 130 and 160 degrees C, the latter two species exist in equilibrium and are the dominant species of tantalum(V). The formation of oxochloride species of tantalum(V) was investigated in mixtures of Pyr14Cl-TaCl5-Na2O (x = 0.65) at various O/Ta mole ratios, and the formation of the oligomeric species with Ta-O-Ta bridging bonds was determined.


[The radiological diagnosis of the male breast. Mammography, sonography and pathohistological correlation].
61 men with breast enlargement underwent mammography; complementary sonography was performed in 34 cases. Diagnoses included gynaecomastia in 53 cases, pseudo-gynaecomastia in 9 cases, 3 carcinomas, 2 inflammatory lesions and 1 lipoma. Gynaecomastias of up to four month's duration are histologically of the florid type and show a nodular or nodular-dendritic mammographic pattern; sonography usually demonstrates a focal hypo-echogenic area. Gynaecomastias of longer duration representing the fibrous type show mammographically a dendritic or diffuse pattern and sonographically a hyper-reflexive breast parenchyma. Mammography and sonography can differentiate reliably true gynaecomastia from pseudo-gynaecomastia. Gynaecomastia and especially inflammatory lesions may not always be readily differentiated from carcinoma. Sonography can be helpful by demonstrating hyper-reflexive glandular tissue, whereas carcinomas are usually hypoechoic.


High loosening rate of the Moje Acamo prosthesis for treating osteoarthritis of the trapeziometacarpal joint.
The Moje Acamo carpometacarpal (CMC) implant is an uncemented large ball-and-socket joint made of a ceramic material coated with a bioactive substance (Bioverit) for osseous fixation. Nine Moje Acamo CMC prostheses were implanted into nine patients with primary osteoarthritis of the thumb CMC joint. At 12 months, three implants had been revised because of progressing pain and osteolysis. In the remaining six patients, radiographs have shown progressive osteolysis around both implants in five patients. These poor results mean that we no longer perform this operation and we recommend close follow-up of all cases that have been performed.


Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration.
The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. To investigate the functions of CYP2S1 in lung cancer. Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.


The Efficacy of Fosbretabulin Disodium Combined with Radiofrequency Ablation in Lung Cancer.
Radiofrequency ablation (RFA) is a technology that uses radiofrequency thermal effect to induce coagulation necrosis of tumor tissue under the guidance of imaging. However, distant metastasis of tumor cells caused by tumor angiogenesis can lead to incomplete tumor clearing. In this study, LLC1 cell line was used for the construction of subcutaneous xenografts. Either 10 mg/kg or 20 mg/kg Fosbretabulin disodium (FBTD) was intragastrically administered every 2 days for a week. RFA was performed at the end of medication. The proportion of T cells was examined by flow cytometry. Serum IgG and IgA levels of mice were examined by ELISA. Expression of certain genes was estimated by qRT-PCR assay. In this study, we demonstrated that FBTD was able to significantly enhance RFA-induced immune function in tumor-bearing mice by upregulating RFA-induced CD8+ killer T cells. Consistently, 10 mg/kg or 20 mg/kg FBTD therapy upregulated the percentage of IFNγ+ and TNFα+ CD8+ tumor infiltrating lymphocytes in tumor-bearing mice compared to the RFA alone or FBTD alone group. Mechanistically, we reported that FBTD inhibited the RFA-induced PD-1 and PD-L1 upregulation in vivo. In conclusion, we demonstrated that FBTD promoted the antitumor effects of RFA in lung tumor-bearing mice in this study.


A calcium-metalloribozyme with autodecapping and pyrophosphatase activities.
A previously-isolated ribozyme with capping activity has self-decapping activity, here characterized alongside its additional, somewhat parallel, pyrophosphatase reaction. Decapping is 10-50 times slower than the pyrophosphatase activity, depending on pH. The RNA accelerates pyrophosphate release 170 000 times over a control composed of randomized pppRNA, and 5' capped RNA accelerates decapping 1000-fold over random capped RNA. Triphosphate-linked G(5')pppRNA also supports an unusual cap-exchange reaction, exchanging its cap with guanosine 5'-tetraphosphate to form pentaphosphate-linked G(5')pppppRNA. GDP, a capping reactant for the RNA, appears to suppress both decapping and pyrophosphatase activities. Autodecapping and pyrophosphatase activities have in common an unusual divalent metal ion requirement for Ca2+ or less effectively Mn2+, and both are active over a broad pH range of 4.5-9. 0. These characteristics resemble the capping activity of the same RNA. Kinetic analysis reveals a well-defined Ca2+-RNA complex, and Mg2+ and Sr2+ act as competitive inhibitors of Ca2+. A strong Ca2+-binding site is suggested by a low KM of 40-60 microM at pH >/= 7.0. The role of Ca2+ in these reactions can be surmized from literature data on reactivity of nucleotide phosphates. Pyrophosphatase, capping, and decapping activities of isolate 6 RNA are apparently carried out by a single reaction center, whose rate of reaction with all nucleophiles sums to a constant total rate. This suggests a universal rate-limiting step. Versatile activation of alpha-phosphate by this reaction center raises the possibility of combinatorial ribozymes.


Clinical and biochemical aspects of "aspirin-sensitivity".
Progressively increasing doses of aspirin (acetylsalicylic acid--ASA) were tolerated by 14 out of 15 patients with confirmed aspirin-sensitive urticaria and in 7 out of 9 patients with aspirin-sensitive asthma. Blood levels of histamine and prostaglandin (PG) F2 alpha were significantly raised in these patients before ASA administration. PGF2 alpha levels fell to within the normal range after challenge doses of ASA which were sufficient to cause symptoms. Skin prick testing with histamine and codeine phosphate did not show evidence of abnormal tissue reactivity or mast cell reactivity. A wider spectrum of mediators will need to be considered if the mechanism of symptom production is to be understood.


Nuclear collective flow and charged-pion emission in Ne-nucleus collisions at E/A = 800 MeV.
Triple-differential cross sections of charged pions were measured for collisions of Ne projectiles at E/A = 800 MeV with NaF, Nb, and Pb targets. The reaction plane was estimated event by event from the light-baryon momentum distribution. For heavy targets, preferential emission of charged pions away from the interaction zone towards the projectile side was observed in the transverse direction. Such a preferential emission, which is not predicted by cascade calculations, may be attributed to a stronger pion absorption by the heavier spectator remnant.


The Role of Specular Reflections and Illumination in the Perception of Thickness in Solid Transparent Objects.
Specular reflections and refractive distortions are complex image properties of solid transparent objects, but despite this complexity, we readily perceive the 3D shapes of these objects (e.g., glass and clear plastic). We have found in past work that relevant sources of scene complexity have differential effects on 3D shape perception, with specular reflections increasing perceived thickness, and refractive distortions decreasing perceived thickness. In an object with both elements, such as glass, the two optical properties may complement each other to support reliable perception of 3D shape. We investigated the relative dominance of specular reflection and refractive distortions in the perception of shape. Surprisingly, the ratio of specular reflection to refractive component was almost equal to that of ordinary glass and ice, which promote correct percepts of 3D shape. The results were also explained by the variance in local RMS contrast in stimulus images but may depend on overall luminance and contrast of the surrounding light field.


Thrombolytic therapy of acute basilar artery occlusion. Variables affecting recanalization and outcome.
Thrombolysis may reduce mortality after acute basilar artery (BA) occlusion. We intended to find variables affecting recanalization and clinical outcome in patients with BA occlusion undergoing thrombolytic therapy. We analyzed in retrospect the clinical and angiographic data of a consecutive series of 51 patients treated with intra-arterial urokinase (n = 44; 0.3 to 1.5 mIU) or intravenous or intra-arterial recombinant tissue plasminogen activator (n = 7; 22 to 100 mg). We identified effective variables by multiple logistic regression analyses and univariate tests. Sites of occlusion were the caudal (n = 23), middle (n = 18), and distal (n = 10) segments of the BA. The pathogenesis was embolism in 35 and local atherothrombosis in 16 patients. Collateral circulation was good in 32 patients and poor or absent in 19 patients. Recanalization was achieved in 26 of 51 (51%) patients and was associated with occlusions of embolic etiology (P = .0025). Mortality was 46% (12/26) in the recanalization group and 92% (23/25) in the nonrecanalization group (P = .0004). Other independent variables affecting mortality were length of BA obstruction (P = .0011), age (P = .0008), and collateral state (P = .0454). After follow-up (median, 32 months), 10 of the 16 survivors were only minimally impaired, with a Barthel Index score of 95 or greater; 5 patients were moderately and 1 severely disabled. Recanalization of acute BA occlusion reduces mortality significantly. Length of BA obstruction and state of the collaterals are additional independent variables affecting survival. Young patients with monosegmental embolic occlusion of the BA seem to have the best chance to considerably profit from thrombolysis.


Thromboelastography in abruptio placentae.
The purpose of this study was to document thromboelastographic (TEG) changes in abruptio placentae and to compare these results with that of conventional tests used to monitor coagulation. This was a prospective study of 30 patients with abruptio placentae. All coagulation investigations including the TEG were performed on admission, immediately following delivery, and after periods of 4 hours and 24 hours. Results showed that standard coagulation tests detected coagulation abnormalities except the platelet count returned to normal limits within 24 hours of delivery. There was strong correlation between fibrinogen levels and the TEG parameters, ma and k time (r=0.8). There was moderate correlation between platelet count and ma (r=0.6). In conclusion, minor abnormalities in the clotting profile are clinically unimportant. The TEG does not detect such minor abnormalities because of its inherent ability to test the coagulation cascade as a whole. Major abnormalities are clinically relevant and the TEG detect 75% of them. Further, the TEG establishes the diagnosis of hypercoagulability an early sign of disseminated intravascular coagulation. Although standard laboratory tests are still necessary to detect coagulation abnormalities on admission, the TEG is a useful test in large obstetric units where laboratory results are not immediately available for the purposes of monitoring and treating ongoing coagulation defects.


Atopy and hand dermatitis in hospital wet work.
The relation of different atopic symptoms to the occurrence of hand dermatitis in employees who perform wet work in hospitals was studied. Atopy was defined as previous or present atopic dermatitis (AD), allergic rhinitis/conjunctivitis or asthma (AMS). In this population the prevalence of atopy was 32% and the frequency of past or present hand dermatitis 44%. Hand dermatitis had occurred in about 65% of persons with atopic symptoms and in 75% of those who had unusually dry, pruritic skin and of those with atopic relatives. Of the other workers only 33% had had skin problems. The presence of atopic symptoms significantly favoured the development of hand dermatitis in these occupations (p less than 0.001).


First Report of leaf spot disease caused by Colletotrichum gloeosporioides on Chaenomeles sinensis in China.
Chaenomeles sinensis is a shrub or small arbor of the genus Chaenomeles in Rosaceae, which is widely planted in China. It is a kind of garden ornamental plant and has high economic value. Since 2020, a leaf disease occurred on the foliage of C. sinensis at the campus of Nanjing Forestry University, Nanjing, China. After investigating, C. sinensis was found with leaf spot disease at a 100% infection rate, which causing gigantic ornamental loss. Leaf spots are round to irregular distributing on the leaves, in addition, the color of spots is brown. There are yellow halos on the edge of the lesion. Small leaf tissues (3 to 4 mm2) from lesion margins were surface sterilized with 75% ethanol for 30s and then rinsed with sterile dH2O for three times. Afterwards, placed on potato dextrose agar (PDA) at 25°C. Pure cultures were obtained by monosporic isolation, and a representative isolate (NJTJ.1) was obtained. When cultured on PDA, the colony of NJTJ.1 was white and cottony. On the reverse side, the color of colony nearly light yellow. The colony were placed in the liquid Carboxymethyl cellulose (CMC) medium. After culturing for 24h in a shaker at 25℃ and 150rmp/min, the spore liquid was taken by us. The conidia were one-celled, straight, hyaline, subcylindrical with rounded ends and measured 15.1 to 23.6× 5.4 to 7.9 µm (n =30). Appressoria were one-celled, brown, thick-walled, ellipsoidal, and measured 7.7 to 13.8 × 6.4 to 10.3 µm (n =30). The morphological characteristics of NJTJ.1 fitted with the description of the Colletotrichhum gloeosporioides complex (Weir et al., 2012). For accurate identification, the internal transcribed spacer (ITS), and the genes encoding glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT) and chitin synthase (CHS-1) were amplified with primers ITS1/ITS4, GDF/GDR, ACT-512F/ACT-783R, and CHS-79F/CHS-345R (Zhu et al, 2019), respectively. The sequences were deposited in GenBank [Accession Nos.MT984264, MW030495 and MW030496 to MW030497 for NJTJ.1]. A Blast search of GenBank showed that ITS, GAPDH, ACT and CHS-1 sequences of NJTJ.1 were 99%, 99%, 100% and 100% identical to those of C. gloeosporioides (MH571757.1 ,KY995355.1 , MN058143.1 and MN313581.1). A neighbor-joining phylogenetic tree was generated by combining all sequenced loci in MEGA7. The isolate NJTJ.1 clustered in the C. gloeosporioides clade with 99% bootstrap support. The pathogenicity of the NJTJ.1 was verified both on detached and living leaves. The detached leaves were inoculated with 5-mm mycelial plugs cut from the edge of 6-day old cultures on PDA and 20 μL of spore suspension (106 conidia/mL) and each treatment had 5 replicates. Controls were treated with sterile dH2O. The inocula were placed at a distance of 2 to 3 cm on the leaves which were wounded with a sterile needle. All of them were placed in 20-cm dishes on wet filter paper at 25°C. After 5 days, all the inoculated points showed lesions which were similar to those outdoor observed. Whereas, controls were asymptomatic.At the same time, the plugs of C. gloeosporioides were inoculated on living leaves.After 7 days, the leaves which were inoculated also appeared lesions. This is the first report of C. gloeosporioides causing leaf blotch on Chaenomeles sinensis in China. These data will help develop effective strategies for managing this disease.


The Enigmatic Role of Lipids in Cilia Signaling.
Primary cilia are specialized cellular structures that project from the surface of most cell types in metazoans and mediate transduction of major signaling pathways. The ciliary membrane is contiguous with the plasma membrane, yet it exhibits distinct protein and lipid composition, which is essential for ciliary function. Diffusion barriers at the base of a cilium are responsible for establishing unique molecular composition of this organelle. Although considerable progress has been made in identifying mechanisms of ciliary protein trafficking in and out of cilia, it remains largely unknown how the distinct lipid identity of the ciliary membrane is achieved. In this mini review, I summarize recent developments in characterizing lipid composition and organization of the ciliary membrane and discuss the emerging roles of lipids in modulating activity of ciliary signaling components including ion channels and G protein-coupled receptors.


Mammogram synthesis using a 3D simulation. II. Evaluation of synthetic mammogram texture.
We have evaluated a method for synthesizing mammograms by comparing the texture of clinical and synthetic mammograms. The synthesis algorithm is based upon simulations of breast tissue and the mammographic imaging process. Mammogram texture was synthesized by projections of simulated adipose tissue compartments. It was hypothesized that the synthetic and clinical texture have similar properties, assuming that the mammogram texture reflects the 3D tissue distribution. The size of the projected compartments was computed by mathematical morphology. The texture energy and fractal dimension were also computed and analyzed in terms of the distribution of texture features within four different tissue regions in clinical and synthetic mammograms. Comparison of the cumulative distributions of the mean features computed from 95 mammograms showed that the synthetic images simulate the mean features of the texture of clinical mammograms. Correlation of clinical and synthetic texture feature histograms, averaged over all images, showed that the synthetic images can simulate the range of features seen over a large group of mammograms. The best agreement with clinical texture was achieved for simulated compartments with radii of 4-13.3 mm in predominantly adipose tissue regions, and radii of 2.7-5.33 and 1.3-2.7 mm in retroareolar and dense fibroglandular tissue regions, respectively.


Magnetic resonance cholangiopancreatography in obstructive jaundice.
To determine the ability of magnetic resonance cholangiopancreatography (MRCP) to diagnose the level and cause of obstruction in patients with obstructive jaundice. The limitations of available imaging modalities have led to the increasing use of MRCP, which is a noninvasive and highly accurate technique in evaluating patients with biliary obstruction. Thirty patients were included in this study. MRCP was done using a fat suppressed, heavily T2 weighted fast spin echo sequence. The MRCP findings were confirmed on surgical exploration or clinical follow-up. MRCP could correctly identify ductal dilatation and the level of obstruction in all cases, except one. All causes of obstruction, except three, were detected. It failed to detect a common bile duct calculus in a minimally dilated ductal system and misdiagnosed a case of focal chronic pancreatitis as carcinoma head pancreas and a small pancreatic head mass as cholangiocarcinoma. It had a sensitivity of 94.44%, specificity of 81.81%, positive predictive value of 89.47%, and negative predictive value of 90% for the detection of malignant causes. The overall diagnostic accuracy for detection of level and cause of obstruction was 96.3% and 89.65%, respectively. The high diagnostic accuracy of MRCP in evaluating patients with obstructive jaundice indicates that it has the potential to become the diagnostic modality of choice in such patients.


Comparative Photographic, Retrospective Analysis of Nonsyndromic Cleft Noses Treated with or without NAM.
Long-term results and efficacy of nasoalveolar molding (NAM) on the perinasal region are reported controversially in the literature. With this study, we demonstrate our experiences, contribute to the ongoing discussion, and describe our decision-making when NAM is indicated or not. Conventional pre- and postinterventional photographs of patients with nonsyndromic unilateral and bilateral cleft lip and palate (UCLP and BCLP) were analyzed. The 2 independent raters were blinded to therapy (NAM versus non-NAM), and 7 parameters were measured. Intraclass correlation coefficient for intra- and interrater reliability was calculated. The Mann-Whitney U test was performed to compare therapy- and appearance-matched pairs. Finally, 30 specialists in cranio-maxillofacial surgery performed a subjective, blinded rating of matched NAM and non-NAM cases. Thirty-six patients, 16 UCLP and 20 BCLP, were enrolled. The intraclass correlation coefficients for intra- and interrater reliability were excellent for all measurements, except for nasal sill (0.77 intrarater and 0.80 interrater). Height-to-width ratio (P = 0.012) was significantly different in the comparison of non-NAM and NAM-treated severe cases with UCLP. Thirty blinded raters evaluated NAM-treated cases with severe UCLP better than matched non-NAM cases. Non-NAM-treated cases with moderate UCLP and BCLP were rated better than matched NAM cases. Children with severe UCLP may benefit from NAM therapy in the sense of better symmetry and a more homogenous appearance. Patients with moderate UCLP and BCLP did not benefit, and the risk of the burden of care increased.


Synthesis and stability of 3-nitro-2-pyridinesulfenyl chloride (NpysCl).
3-Nitro-2-pyridinesulfenyl chloride (NpysCl) is the starting material for the synthesis of N-, O- and S-Npys-protected amino acids. Two efficient, novel synthetic routes to NpysCl are described. The stability of NpysCl was determined in a variety of solvents, with and without base, to determine the most suitable solvent and base for the synthesis of N-Npys amino acids. The syntheses of Npys-Ala and Boc-Lys(Npys) tert-butylammonium salt are also described.


Microbial composition and omasal flows of bacterial, protozoal, and nonmicrobial amino acids in lactating dairy cows fed fresh perennial ryegrass (Lolium perenne L.) not supplemented or supplemented with rolled barley.
The objective of this study was to evaluate the effect of rolled barley supplementation on microbial composition and omasal flows of bacterial, protozoal, and nonmicrobial AA in cows fed fresh perennial ryegrass (Lolium perenne L.; PRG). Ten ruminally cannulated multiparous Holstein cows averaging (mean ± standard deviation) 49 ± 23 d in milk and 513 ± 36 kg of body weight were assigned to 1 of 2 treatments in a switchback design. The treatment diets were PRG only or PRG plus 3.5 kg of dry matter rolled barley (G+RB). The study consisted of three 29-d periods where each period consisted of 21 d of diet adaptation and 8 d of data and sample collection. A double-marker system was used to quantify nutrient flow entering the omasal canal along with 15N-ammonium sulfate to label and measure the microbial and nonmicrobial omasal flow of AA. Overall, rolled barley supplementation had no effect on the AA composition of the omasal liquid-associated and particle-associated bacteria. Rolled barley supplementation affected the AA concentrations of omasal protozoa; however, the differences were nutritionally minor. Particle-associated bacteria AA flow was increased for all AA, except for Trp and Pro, in cows fed the G+RB diet. Rolled barley supplementation had no effect on protozoal AA flow. On average, protozoa accounted for 23% of the microbial essential AA flow, which ranged from 17 to 28% for Trp and Lys, respectively. The flow of all AA in omasal true digesta increased in cows fed the G+RB diet compared with the PRG-only diet, resulting in a 228 g/d increase in total AA flow in cows fed the G+RB diet. This increase in total AA flow in cows fed the G+RB diet was due to an increase in microbial AA flow. Rolled barley supplementation had no effect on nonmicrobial AA flow. The nonmicrobial AA flow modestly contributed to total AA flow, accounting for 15.6% on average. These results indicated that extensive ruminal degradation of PRG AA occurred (83.5%), and we demonstrated that cows consuming PRG-based diets exhibit a large dependence on microbial AA to support metabolizable AA supply. Rolled barley supplementation can increase the omasal flow of microbial AA in cows consuming PRG-based diets. However, further research is required to elucidate if this increased AA supply can support higher milk yield under such dietary conditions.


[Interferon-alpha and auto-immunity].
To assess the role of endogenous interferon alpha (IFN) in auto-immune experimental models and human diseases, and to evaluate its iatrogenic potential as a therapeutic agent. IFN is a cytokine involved in cellular immunity, that promotes both differentiation of dendritic cells and the TH1 pathway. Auto-immune side-effects of recombinant IFN depend on IFN dosage and the pathology concerned. The spectrum extends from occurrence of auto-antibodies in an asymptomatic patient to overt disease such as systemic lupus. Antigenic targets of auto-antibodies are diverse: blood cells coagulation factors, immunoglobulin, hormones, intrinsic factor, intracellular components. Thyroiditis is the most frequently reported auto-immune disease occurring during IFN treatment, including hypothyroidism, hyperthyroidism or a bi-phasic pattern. Currently, true incidence of thyroiditis remains debated. It appears very low (under 1%) in hepatologic series using low-dose IFN. The fact that auto-immunity may be related to the treated disease--before use of IFN--must also be addressed: e.g. antinuclear factors and anti-DNA antibodies in chronic myeloid leukemia or anti-actin and anti-LKM antibodies in chronic C hepatitis. Recombinant alpha interferon appears more as a trigger than a de novo inducer of auto-immune disorders. Its use as an immunomodulator agent should be treated with caution.


An Approach to a Patient With Primary Hyperparathyroidism and a Suspected Ectopic Parathyroid Adenoma.
Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia driven by excess parathyroid hormone (PTH) secretion. PHPT is a common endocrine condition with a prevalence of 1 to 7 cases per 1000 adults. PHPT typically presents in the fifth or sixth decade and shows significant female preponderance. Solitary hyperfunctioning parathyroid adenomas account for 85% to 90% of PHPT cases. The remaining 10% to 15% include cases of multiglandular disease (multiple adenomas or hyperplasia) and, rarely, parathyroid carcinoma (1%). Ectopic parathyroid adenomas may arise due to abnormal embryological migration of the parathyroid glands and can be difficult to localize preoperatively, making surgical cure challenging on the first attempt. The potential existence of multiglandular disease should be considered in all patients in whom preoperative localization fails to identify a target adenoma or following unsuccessful parathyroidectomy. Risk factors for multiglandular disease include underlying genetic syndromes (eg, MEN1/2A), lithium therapy, or previous radiotherapy. In addition to multifocal disease, the possibility of an ectopic parathyroid gland should also be considered in patients requiring repeat parathyroid surgery. In this article, we use illustrative clinical vignettes to discuss the approach to a patient with primary hyperparathyroidism (PHPT) and a suspected ectopic parathyroid adenoma.


Protein targets of thiazolidinone derivatives in Toxoplasma gondii and insights into their binding to ROP18.
Thiazolidinone derivatives show inhibitory activity (IC50) against the Toxoplasma gondii parasite, as well as high selectivity with high therapeutic index. To disclose the target proteins of the thiazolidinone core in this parasite, we explored in silico the active sites of different T. gondii proteins and estimated the binding-free energy of reported thiazolidinone molecules with inhibitory effect on invasion and replication of the parasite inside host cells. This enabled us to describe some of the most suitable structural characteristics to design a compound derived from the thiazolidinone core. The best binding affinity was observed in the active site of kinase proteins, we selected the active site of the T. gondii ROP18 kinase, because it is an important factor for the virulence and survival of the parasite. We present the possible effect of a derivative of thiazolidinone core in the active site of T. gondii ROP18 and described some characteristics of substituent groups that could improve the affinity and specificity of compounds derived from the thiazolidinone core against T. gondii. The results of our study suggest that compounds derived from the thiazolidinone core have a preference for protein kinases of T. gondii, being promising compounds for the development of new drugs with potential anti-toxoplasmosis activity. Our findings highlight the importance of use computational studies for the understanding of the action mechanism of compounds with biological activity.


High gene flow maintains genetic diversity following selection for high EPSPS copy number in the weed kochia (Amaranthaceae).
Kochia, a major weed species, has evolved resistance to four herbicide modes of action. Herbicide resistance appears to spread quickly, which could result in diminished standing genetic variation, reducing the ability of populations to adapt further. Here we used double digest restriction enzyme associated sequencing to determine the level of gene flow among kochia populations and whether selection for glyphosate resistance reduces genetic variation. Canadian Prairie populations show little to no genetic differentiation (FST = 0.01) and no correlation between genetic and geographic distance (r2 = - 0.02 p = 0.56), indicating high gene flow and no population structure. There is some evidence that kochia populations are genetically depauperate compared to other weed species, but genetic diversity did not differ between glyphosate susceptible and resistant populations or individuals. The inbreeding coefficients suggest there are 23% fewer heterozygotes in these populations than expected with random mating, and no variation was found within the chloroplast. These results indicate that any alleles for herbicide resistance can be expected to spread quickly through kochia populations, but there is little evidence this spread will reduce the species' genetic variation or limit the species' ability to respond to further selection pressure.


Gentamicin treatment in exercised mdx mice: Identification of dystrophin-sensitive pathways and evaluation of efficacy in work-loaded dystrophic muscle.
Aminoglycosides force read through of premature stop codon mutations and introduce new mutation-specific gene-corrective strategies in Duchenne muscular dystrophy. A chronic treatment with gentamicin (32 mg/kg/daily i.p., 8-12 weeks) was performed in exercised mdx mice with the dual aim to clarify the dependence on dystrophin of the functional, biochemical and histological alterations present in dystrophic muscle and to verify the long term efficiency of small molecule gene-corrective strategies in work-loaded dystrophic muscle. The treatment counteracted the exercise-induced impairment of in vivo forelimb strength after 6-8 weeks. We observed an increase in dystrophin expression level in all the fibers, although lower than that observed in normal fibers, and found a concomitant recovery of aquaporin-4 at sarcolemma. A significant reduction in centronucleated fibers, in the area of necrosis and in the percentage of nuclear factor-kB-positive nuclei was observed in gastrocnemious muscle of treated animals. Plasma creatine kinase was reduced by 70%. Ex vivo, gentamicin restored membrane ionic conductance in mdx diaphragm and limb muscle fibers. No effects were observed on the altered calcium homeostasis and sarcolemmal calcium permeability, detected by electrophysiological and microspectrofluorimetric approaches. Thus, the maintenance of a partial level of dystrophin is sufficient to reinforce sarcolemmal stability, reducing leakiness, inflammation and fiber damage, while correction of altered calcium homeostasis needs greater expression of dystrophin or direct interventions on the channels involved.


Production of a monoclonal antibody (K 931) to a squamous cell carcinoma associated antigen identified as the 17-1A antigen.
During our efforts to develop monoclonal antibodies (MAbs) to tumor associated surface antigens of squamous cell carcinomas of the head and neck, monoclonal antibody K 931 was produced. The high affinity antibody (Ka 5.0 x 10(10) M-1) showed reactivity with 58 out of 62 squamous cell carcinomas of the head and neck. In contrast normal squamous epithelium as found in epidermis, oral cavity, epiglottis, pharynx, larynx and esophagus did not express the antigen. All other tested epithelial (simple and transitional) tissues did express the antigen, but non-epithelial tissues were negative. Further characterization revealed that the antigen represents the 17-1A antigen. A not earlier reported, enhanced expression of the 17-1A antigen was observed among some primary and all metastatic SCC.


Selection of sequences recognized by a DNA binding protein using a preparative southwestern blot.
We have tested the feasibility of using a preparative scale Southwestern blot to select DNA sequences specifically recognized by a DNA binding protein. We constructed a library of random 15-mer oligonucleotides and screened it using a preparative Southwestern blot with the transcriptional repressor, PRDI-BF1. Several sequences specifically recognized by PRDI-BF1 were isolated. All of these sequences are similar to PRDI, a regulatory element previously demonstrated to bind PRDI-BF1.


[Human bocavirus: studies in the literature and in Chile].
The human bocavirus (HBoV), virus of the Parvoviridae family, discovered by molecular methods in 2005, has been reported in respiratory samples, stool, urine and blood, both in children and adults. Prevalence rates range from 0.8% in fecal samples of individuals with acute diarrhea, up to 19% in respiratory samples and blood. HBoV has been detected in up to 43% of nasopharyngeal samples in asymptomatic children. In Chile, HBoV was detected in 24.2% of nasopharyngeal swabs in children under 5 years of age with respiratory symptoms of which 74% had coinfection with other viruses. In asymptomatic children under 5 years of age, 37.5% of NP samples were positive for HBoV. We discuss the role of HBoV as a causal agent of respiratory and/or enteric disease in light of the high rates of coinfection and asymptomatic infections.


Biochemical and vascular aspects of pediatric chronic fatigue syndrome.
To evaluate the biochemical and vascular aspects of pediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Cross-sectional clinical study. Tayside, Scotland, United Kingdom. Twenty-five children with CFS/ME and 23 healthy children recruited from throughout the United Kingdom. Participants underwent a full clinical examination to establish a diagnosis of CFS/ME and were asked to describe and score their CFS/ME symptoms. Biochemical markers were measured. Arterial wave reflection was estimated to assess systemic arterial stiffness. Markers of oxidative stress and free radicals, C-reactive protein level, white blood cell apoptosis, and arterial wave reflection. Children with CFS/ME had increased oxidative stress compared with control individuals (isoprostanes: 252.30 vs 215.60 pg/mL, P = .007; vitamin C, mean [SD]: 0.84 [0.26] vs 1.15 [0.28] mg/dL, P < .001; vitamin E, 8.72 [2.39] vs 10.94 [3.46] microg/mL, P = .01) and increased white blood cell apoptosis (neutrophils: 53.7% vs 35.7%, P = .005; lymphocytes: 40.1% vs 24.6%, P = .009). Arterial stiffness variables did not differ significantly between groups (mean augmentation index, -0.57% vs -0.47%, P = .09); however, the derived variables significantly correlated with total (r = 0.543, P = .02) and low-density lipoprotein (r = 0.631, P = .004) cholesterol in patients with CFS/ME but not in controls. Biomedical anomalies seen in adults with CFS/ME-increased oxidative stress and increased white blood cell apoptosis-can also be observed in children with clinically diagnosed CFS/ME compared with matched controls. Unlike in their adult counterparts, however, arterial stiffness remained within the reference range in these pediatric patients.


Partial orchiectomy and testis intratubular germ cell neoplasia: World literature review.
Approximately 5% of all patients diagnosed with testicular cancer may have contralateral intratubular germ cell neoplasia (ITGCN) and may develop contralateral germ cell tumor. Here, we present a historical review and current literature regarding ITGCN and partial orchiectomy. The PubMed world literature search was performed for articles written in the English language. Search terms used were: Partial orchiectomy and ITGCN, with a return of 322 articles. Articles obtained were from the United States, Germany, Denmark and the Netherlands as well as a few case reports from Australia, France, Turkey and Spain. A critical review of the literature was performed. Partial orchiectomy is an option for the management of testicular malignancy in a select group of patients in whom radical orchiectomy is not desirable, including those with a solitary testicle, bilateral concurrent malignancies and a desire for paternity or being independent from androgen supplementation. Reports have demonstrated the feasibility of partial orchiectomy, but there are strict surgical criteria; tumor less than 2 cm in size, maintenance of cold ischemia, meticulous dissection to maintain testicular blood supply and biopsying of adjacent testicular parenchyma to ensure negative margins and absence of concurrent ITGCN. Partial orchiectomy is followed by testicular irradiation of 18-20 Gy; this radiation dose reduces fertility but maintains leydig cell function with androgen independence. Patients with a history of testicular carcinoma have a 5% chance of developing a metachronous contralateral tumor. Partial orchiectomy is a technically challenging procedure that requires close follow-up, but may represent a reasonable management option in selected patients.


Localization of the proton pump of corn coleoptile microsomal membranes by density gradient centrifugation.
Previous studies characterizing an ATP-dependent proton pump in microsomal membrane vesicles of corn coleoptiles led to the conclusion that the proton pump was neither mitochondrial nor plasma membrane in origin (Mettler, Mandala, Taiz 1982 Plant Physiol 70: 1738-1742). To facilitate positive identification of the vesicles, corn coleoptile microsomal membranes were fractionated on linear sucrose and dextran gradients, with ATP-dependent [(14)C]methylamine uptake as a probe for proton pumping. On sucrose gradients, proton pumping activity exhibited a density of 1.11 grams/cubic centimeter and was coincident with the endoplasmic reticulum (ER). In the presence of high magnesium, the ER shifted to a heavier density, while proton pumping activity showed no density shift. On linear dextran gradients, proton pumping activity peaked at a lighter density than the ER. The proton pump appears to be electrogenic since both [(14)C]SCN(-) uptake and (36)Cl(-) uptake activities coincided with [(14)C] methylamine uptake on dextran gradients. On the basis of density and transport properties, we conclude that the proton pumping vesicles are probably derived from the tonoplast. Nigericin-stimulated ATPase activity showed a broad distribution which did not coincide with any one membrane marker.


The gender injustice of abortion laws.
This commentary is a response to Katarzyna Sękowska-Kozłowska's article on the treatment of criminal abortion laws as a form of sex discrimination under international human rights law through a study of the communications, Mellet v. Ireland and Whelan v. Ireland. The commentary offers a reading of these communications, and specifically the sex discrimination analysis premised on inequalities of treatment among women, as an engagement with the structural discrimination that characterises abortion laws, and as a radical vision for gender justice under international human rights law.


The effects of guided tissue regeneration membrane placement on healthy periodontal sites.
This study investigates the effects of the placement of a bioresorbable Type I collagen barrier on clinically healthy sites. Ten human subjects, with at least one pair of matched periodontal defects included in a previous study, were investigated for the effect of guided tissue regeneration (GTR) membrane placement on adjacent healthy sites. Control sites consisted of open flap debridement, while experimental sites consisted of similar debridement procedures with placement of a collagen membrane for GTR. The membrane placement was designed to completely cover the periodontal defect, and therefore of necessity overlapped adjacent periodontally healthy sites. It is these healthy sites that are included in the present study. Standardized measurements of change in probing attachment levels were obtained at the time of surgery and 1 year later. The differences in change of clinical attachment levels (CAL) were compared utilizing the Student t-test for paired samples. The mean loss of CAL in the control sites was 1.00 +/- 1.179 mm, and in the test sites was 0.60 +/- 1.729 mm. When comparing the difference in changes of CAL in both test and control sites, there was no statistical significance. There was, however, a wide range of changes between individual sites, which might suggest a clinically meaningful change of CAL on an individual tooth basis. The results of this study suggest that the placement of a bioresorbable collagen barrier has no significant effect on CAL in healthy areas.


[The quality of life of patients with strokes: from the point of view of factors which may affect it].
To evaluate the effect of clinical and psychosocial factors on the quality of life of patients with stroke. A non-experimental transverse study was done on 39 patients with strokes seen in the cerebrovascular diseases clinic of the Institute de Neurología y Neurocirugía in La Havana (Cuba). We recorded data on clinical variables (age, sex, race, previous illnesses, type of stroke, vascular territory, classification of prognosis, etiopathogenesis and function on the Rankin scale) and on psychosocial variables (pattern of behavior, anxiety as a feature and state, depression, manner of coping and social support received). Correlations were established with the dependent variable Quality of life, evaluated on the Nottingham Health Profile. Of the clinical variables there was no correlation with age, female sex was related to greater isolation and the presence of diabetes mellitus with less energy. Greater isolation was seen to be correlated with increased score on the Rankin scale, but this association was not statistically significant. Similarly the clinical characteristic of anxiety was related to greater difficulty in sleeping, as also occurred in depression. The latter was also associated with less energy and greater social isolation. The characteristics of self-control, acceptance of responsibility and positive reevaluation had a positive relation with energy and physical mobility. The greater the social support, especially in the area of health, the better the quality of life in the realms of pain, sleep and social isolation. The psychosocial aspects had more influence on the quality of life of these patients than the clinical factors did.


Antisense inhibition of R-cognin expression modulates differentiation of retinal neurons in vitro.
Retina cognin (R-cognin) is a 50 kDa membrane-associated polypeptide expressed during retinogenesis where it is involved in mediating tissue-specific cell-cell interactions. In addition to its intercellular role in aggregation, R-cognin may act as a cell surface signaling molecule. An antisense oligonucleotide was used to inhibit R-cognin expression and to investigate the effects of this inhibition on subsequent neuronal differentiation. Cultures of retina cells were prepared from 6 day (E6) and 8 day (E8) chicken embryos and were incubated with a deoxyoligonucleotide complimentary to 20 bases of the sequence encoding R-cognin or random oligonucleotides. The levels of choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD), markers of cholinergic and GABAergic differentiation, respectively, were detected by Western blots on protein extracts from treated cultures. The antisense treatment inhibited ChAT levels at E6 and GAD levels at E8. The treatment resulted in no decrease in the level of the enzyme glyceraldehyde 3-phosphate dehydrogenase. A random oligonucleotide did not affect the levels of any of the proteins. These results confirm the cell recognition role of R-cognin and suggest that it is important in intracellular signaling cascades necessary for normal retina development.


Working Memory in Aphasia: Considering Discourse Processing and Treatment Implications.
Evidence suggests that persons with aphasia (PWAs) present with working memory impairments that affect a variety of language tasks. Most of these studies have focused on the phonological loop component of working memory and little attention has been paid to the episodic buffer component. The episodic buffer, as a limited capacity, multimodal system that binds and integrates information from the phonological loop, visuospatial sketchpad, and long-term memory would likely be involved in discourse processing. The purposes of this article were to (1) review discourse level deficits associated with aphasia, (2) describe how a deficit at the level of the episodic buffer could cause such deficits, (3) to review discourse treatment approaches for PWAs, and (4) present preliminary results from a novel discourse treatment study for PWAs.


Overview of 12 months anaesthetic activity in a UK field hospital on enduring operations in Iraq.
The British Field Hospital facility in Southern Iraq has seen a continuous turnover of patient admissions since the start of offensive operations during the 2003 Gulf conflict (Operation TELIC). During the war a number of procedures were carried out and these have been well described to date. On May 1st 2003 President Bush declared an end to high intensity operations with a subsequent reduction in medical activity. However, the facility has continued to provide medical care to large numbers of service and civilian patients from the end of hostilities to the present day. The purpose of this review is to present anaesthetic and demographic data relating to procedures carried out at the Field Hospital over a 12-month period from the end of the war-fighting phase of the conflict.


[Atorvastatin in primary prevention].
Statins are one of the most widely used drugs in medical treatment and have been shown to prevent cardiovascular disease or reduce risk in a large number of studies. Although there is a general class effect, there are differences with regard to structure and efficacy between these agents. Among these agents, atorvastatin is a potent statin whose efficacy has been demonstrated in many clinical trials. Despite the presence of numerous clinical studies, data on atorvastatin related to primary prevention are limited compared to secondary prevention. In this article, clinical results of primary prevention trials with atorvastatin and data on its cost-effectiveness are reviewed. It is concluded that atorvastatin has a role in primary prevention and the cost of its use seems to be lower than commonly accepted cost-effectiveness thresholds.


Role of the glutamatergic system in nicotine dependence : implications for the discovery and development of new pharmacological smoking cessation therapies.
Preclinical research findings in laboratory animals indicate that the glutamatergic system is critically involved in nicotine dependence. In animals, compounds that decrease glutamatergic neurotransmission, such as antagonists at postsynaptic NMDA receptors, antagonists at excitatory postsynaptic metabotropic glutamate (mGlu) 5 receptors, or agonists at inhibitory presynaptic mGlu(2) and mGlu(3) receptors, decreased nicotine self-administration or reinstatement of nicotine-seeking behaviour. These findings suggest that medications that decrease glutamatergic transmission overall may reduce the reinforcing effects of tobacco smoking and prevent relapse to tobacco smoking in humans. Furthermore, compounds that increase glutamate release, such as antagonists at mGlu(2) and mGlu(3) receptors, ameliorated reward deficits associated with nicotine withdrawal in animals, and thus may alleviate the depression-like symptoms associated with nicotine withdrawal in humans. Animal studies also showed that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptors did not appear to be involved in mediating the primary reinforcing effects of nicotine but that they may be involved in the development of nicotine dependence and withdrawal.Taken together, the preclinical data indicate that different glutamatergic receptors are involved in the mediation of different aspects of nicotine dependence. These findings have implications for the discovery and development of new pharmacotherapies that target the glutamatergic system to aid in smoking cessation. At present, very few clinical studies have addressed the effects of glutamatergic compounds on cigarette smoking. Clinical studies involving compounds that have actions at ionotropic glutamate receptors are briefly discussed in this review and suggest the potential of glutamatergic compounds as pharmacotherapies to aid in smoking cessation. Medications that target mGlu receptors have recently been tested in human phase II trials for various indications; however, the potential of these mGlu compounds as medications for nicotine dependence remains to be evaluated in humans. The preclinical data evaluated in this review indicate that such clinical trials for smoking cessation with mGlu compounds are clearly warranted and may reveal novel treatments for nicotine dependence.


T lymphocyte colonies are the progeny of single cells.
T lymphocyte colonies, arising from phytohemagglutinin (PHA) stimulated mononuclear cells cultured in a semi-solid agar matrix, could be the progeny of single cells (monoclonal) or of multiple cells (polyclonal). We have conducted several studies to determine if these colonies are monoclonal or polyclonal in origin. Normal human peripheral blood mononuclear cells from male-female, HLA-A and B disparate donor pairs were incubated for 18 h in RPMI 1640 containing PHA and fetal calf serum (FCS) and then cultured in a two-layer semi-solid agar system. After 5 days of incubation, the clonality of the colonies was assessed by in situ Y chromatin analysis, and by analysis of HLA-A and B locus antigens. Overlayers were stained with quinicrine dihydrochloride and the number of cells in the T cell colonies with Y chromatin enumerated using fluorescence microscopy. In other studies, colonies were picked from the agar with a capillary pipette and expanded in culture media. After 17 days of culture, cells were harvested and HLA-A and B phenotypes were determined. The results indicate that 87% of the T cell colonies had cells of either male or female origin. In addition, 90% of the colonies possessed HLA-phenotypes of only one donor. We conclude that Y chromatin and HLA analysis of individual colonies from cocultures suggest the monoclonality of T lymphocyte colonies.


Experimental and clinical studies of Kienböck's disease. Excision of the lunate followed by packing of the free tendon.
In late cases of Kienböck's disease in which the lunate is diminished in size, implant arthroplasty cannot give good results. Carroll developed the autogenous tendon graft in 1970. We have utilized this technique in 35 cases with generally satisfactory results. In order to clarify the rationale of this procedure, the fate of the packed free tendon was studied experimentally using four rhesus monkeys and 40 rabbits. The animals were serially sacrificed, and observations were made, revealing that the packed tendon moulded itself to the surrounding articular surfaces. Histologically, it became gradually collagenized and finally hyalinized, to act as a good spacer.


[The evaluation of nasal ventilation in allergic rhinitis patients after nasal provocation].
To evaluate nasal ventilation in allergic rhinitis patients after nasal provocation with acoustic rhinometry. Twenty AR cases were selected. Each one was assessed for the nasal cavity volumes (NCV), nasal airway resistance (NR), nasal minimal cross-section area (NMCA) and distance of nasal minimal cross-section area from nostril (DCAN) by using acoustic rhinometry before and after nasal provocation 1 hour and 6 hours later. The results were statistically analyzed. After nasal provocation 1 hour 1 later, NCV and NR had a significant difference compared with before nasal provocation(P<0. 05), but NMCA and DCAN had no difference (P > 0.05). After 6 hours later, NCV, NR, NMCA and DCAN had a significant difference compared with before nasal provocation (P < 0.05). NCV,NR,DCAN had a significant difference between 1 hour later and 6 hours later after provocation (P < 0.05), while NMCA had no difference (P > 0.05). The nasal ventilation in allergic rhinitis after nasal provocation had declined over time.


Coaches. A missing link in the health care system.
The number of children and adolescents who participate in interscholastic athletics demands attention to the quality of the coaching they receive and to the opportunities that the athlete-coach relationship provides for modification of high-risk behaviors, social skills training, and character formation. Although the need for coaches has increased due to the advent of girls' athletic programs, which was mandated by Title IX legislation, only a minority of states require certification for coaches who work in school systems. Four coaching curricula are summarized and contrasted: the American Coaching Effectiveness Program, the curriculum of the National Youth Sports Coaches Association, the Athletic Health Care System, and the Coach Effectiveness Training Program. Recommendations for coach certification by states, physician advocacy for coaching standards, and improved sports medicine services are discussed.


Controlling Hydrogel Properties by the Cooperative Harvesting of the Components of Sunlight.
The utilization of the full spectrum of sunlight from ultraviolet to infrared to cooperatively control the properties of hydrogels is the key to developing efficient sunlight-responsive hydrogels, but there are significant challenges. The photoresponsive hydrogel developed here formed by azobenzene-containing polyzwitterionic chains possesses capabilities for simultaneously utilizing light from the ultraviolet to the infrared to cooperatively facilitate the gel-to-sol transitions. The ultraviolet and visible light can be converted into mechanical energy simultaneously to synergistically power the dynamic wagging of azobenzene groups, while the infrared light can be converted into kinetic energy of the zwitterionic groups to promote the wagging of the azobenzene groups. Cooperative action between the major components of sunlight can be applied to control a range of important properties of the hydrogel including wettability, adhesion, molecular release, self-healing, and mineralization. The work presented here demonstrates a novel strategy for harvesting all the major components of sunlight to control the properties of photoresponsive materials.


Standardization of smallpox vaccines and the eradication programme--a WHO perspective.
Smallpox vaccine was born in 1796 and the need for it ended in 1980 with the eradication of smallpox. What was remarkable was that in its 200 years history, when the global smallpox eradication programme really needed the vaccine in 1967, it was found that, on the whole, quality was unsatisfactory and supply was short. Unconventional counter measures were taken by WHO, including an international independent testing system, provision of reference preparations in large quantity etc. They effectively solved the problems meeting the target eradication schedule of 10 years. The lessons learned would be of some value to the future eradication or effective control programme of vaccine preventable diseases.


Down-regulation of major histocompatibility complex Q1b gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
We analyzed mouse hepatoma cells using differential display to discover new genes that respond to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We identified a class I major histocompatibility complex (MHC) gene, which we designated as MHC Q1b, whose expression decreases in the presence of TCDD. TCDD-induced down-regulation of MHC Q1b requires both the aromatic hydrocarbon receptor and the aromatic hydrocarbon receptor nuclear translocator, transcription factors that up-regulate other genes in response to TCDD. Down-regulation of MHC Q1b by TCDD appears to involve both transcriptional and post-transcriptional regulatory events; the post-transcriptional destabilization of MHC Q1b mRNA is probably a secondary response to TCDD. Our findings reveal new mechanistic aspects of gene regulation by TCDD. In addition, our observations suggest a mechanism that might account for some of TCDD's immunotoxic effects.


Reduced immunostaining for the extracellular Ca2+-sensing receptor in primary and uremic secondary hyperparathyroidism.
Most parathyroid adenomas and some pathological parathyroid glands from patients with primary parathyroid hyperplasia or severe uremic secondary/tertiary hyperparathyroidism show an elevated set-point [the extracellular Ca2+ concentration (Ca2+o) half-maximally inhibiting PTH secretion]. In the present study, we investigated whether expression of the Ca2+o-sensing receptor protein recently cloned from bovine parathyroid, a key component in Ca2+o-regulated PTH release, is altered in primary and uremic hyperparathyroidism. Using immunohistochemistry with specific antireceptor antibodies, we compared immunoreactivity of the receptor protein in 14 adenomas, biopsies of 24 normal glands from this same group of patients, and 8 hyperplastic parathyroid glands from 2 individuals with uremic hyperparathyroidism. The results show a substantial reduction in the intensity of immunostaining for the receptor protein that averaged nearly 60% for both adenomas and hyperplastic glands, as quantitated by image analysis. Although normal glands from normocalcemic controls were not available, the intensity of receptor staining in normal glands from patients with adenomas was comparable to that in normal bovine, rat, and mouse parathyroid glands. There was considerable variation in staining intensity among different pathological parathyroid glands, even in those from the same patient with secondary hyperparathyroidism. In addition, both adenomas and hyperplastic glands had, in some cases, isolated chief cells and groups of cells, sometimes around the periphery of an abnormal gland, with receptor staining equivalent to that of normal parathyroid cells, whereas the bulk of the cells in the same gland showed a marked decrease in staining. Thus, there is a variable, but substantial, reduction in the immunoreactivity of the Ca2+o-sensing receptor protein in both parathyroid adenomas and uremic hyperparathyroidism, as assessed by immunohistochemistry, that probably results from reduced expression of the receptor protein and may contribute to the increase in the set-point often observed in these patients.


Circadian variation of alpha 1-adrenoceptor-mediated pressor response to phenylephrine in man.
The variability in the pressor effects of the alpha 1-adrenoceptor agonist phenylephrine was observed under placebo conditions in ten healthy subjects in a double blind randomized study. Phenylephrine infusions were administered before administration of placebo (baseline) and 2, 4, 8, 12, 24 and 48 h later. The doses of phenylephrine required to increase systolic blood pressure by 20 mmHg after 8 and 12 h (5.30 and 9.30 pm, 81.4 +/- 15.3 and 71.1 +/- 16.0 micrograms min-1, respectively) were significantly (P < 0.01) less than the baseline values (8.30 am, 108.0 +/- 27.6 g min-1). These results might indicate a circadian variation in the phenylephrine-induced alpha-adrenoceptor-mediated vascular response in healthy subjects. These observations lend further insight into circadian variations of vascular tone that might contribute to circadian rhythms in cardiovascular disease.


Blood activities of antioxidant enzymes in alcoholics before and after withdrawal.
Since free radicals and peroxides seem to be involved in the toxicity of alcohol, several authors have examined the variations of blood activities of antioxidant enzymes in alcoholics, but published results are somewhat conflicting. In this study, erythrocyte (E) activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT), and plasma (P) activities of SOD and GPX were measured in 58 male alcoholics without evidence of severe liver disease before and after a 21-day weaning period, and in a control group of 78 healthy men. Before abstinence, E-SOD and E-GPX activities were, respectively, 6.8% and 13.0% lower in alcoholics than in controls (p < or = .05 and p < or = .01, respectively), whereas the slight increases of E-CAT, P-SOD and P-GPX were not statistically significant. After 21 days of abstinence, no change in activities of the erythrocyte enzymes was noticed; conversely, P-SOD activity was reduced by 8.3% (p < or = .01) and P-GPX by 23.3% (p < or = .001). Variations of blood antioxidant enzymes observed in patients were of limited amplitude and do not allow the use of either of them as markers of alcohol abuse.


[RETRACTILE MESOCOLONITIS: PATHOPHISIOLOGY AND COMPLICATIONS]
The mesentery and mesocolon are structures with suspensory functions of the small bowel and colon respectively. When they are involved by prominent fibroblastic proliferation tissue, this is know as retractile mesenteritis and retractile mesocolonitis. The retractile mesocolonitis is associated with sigmoid volvulus, and is a common finding in the rural areas of Puno (Peru). The common macroscopic appearance consists of a markedly thickened mesentery of rubbery consistency, and the retraction predisposing a twist of the bowel. The histologic features include fibrosis with massive accumulation of dense collagenous tissue. These lesions can be the expression of a reparative proccess that occurs in response to mesenteric injury of enteric bacteria (bacterial transiocation) or inflammatory response. Repeated attacks of bacterial colitis might lead to scarring of the mesocolon.


Diversity among posterior thalamoperforating branches originated from P1 segment: systematic review.
The P1 segment of the posterior cerebral artery (PCA) begins at the termination of the basilar artery and ends at the origin of posterior commu-nicating artery, within the interpeduncular cistern. Perforating branches arising from this segment are called posterior thalamoperforating arteries (TPAs) and the main and biggest artery among those is called TPA. Perforating branches are a crucial component of cerebrovascular system supplying the posterior part of the thalamus, subthalamus, hypothalamus, substantia nigra, perforated substance, posterior part of internal capsule and the nucleus of III and IV cranial nerve. It is very important for neurosurgeon to know the anatomy of perforating branches because of their susceptibility to injury. The aim of this study is to determine the morphometry of posterior TPAs and allow a better understanding of their bran-ching patterns and relation to basilar artery. An extensive search was undertaken in order to identify published literature related to the posterior cerebral circulation system and the anatomy of posterior TPAs using key words. Medline, Embase, Ovid and Google Scholar databases were searched for publications dated from 1970 until July 2016. We collected and analysed all the data describing the mean number of branches per P1 segment, range of branches, number of analysed PCA, largest diameter of TPA, mean diameter of TPA and average distance from the basilar artery bifurcation. Thirteen cadaver studies were analysed and the data was extracted. We focused on the mean number of branches arising from P1 segment, perforators range, mean diameter of perforating branches, largest diameter of perforating branches. Mean number of branches per hemisphere was 2.91 (min. 1.51, max. 4.1). In more than half of analysed studies, authors did not find any pre-sence of posterior TPAs. Mean diameter of those perforators was 0.51 mm (min. 0.125 mm, max. 0.8 mm). Average distance from basilar artery bifurcation was 2.29 mm (min. 1.93 mm, max. 2.75 mm). There were many branching patterns presented by different authors.


Impairment of Base Excision Repair in Dermal Fibroblasts Isolated From Nevoid Basal Cell Carcinoma Patients.
The nevoid basal cell carcinoma syndrome (NBCCS), also called Gorlin syndrome is an autosomal dominant disorder whose incidence is estimated at about 1 per 55,600-256,000 individuals. It is characterized by several developmental abnormalities and an increased predisposition to the development of basal cell carcinomas (BCCs). Cutaneous fibroblasts from Gorlin patients have been shown to exhibit an increased sensitivity to ionizing radiations. Mutations in the tumor suppressor gene PTCH1, which is part of the Sonic Hedgehog (SHH) signaling pathway, are responsible for these clinical manifestations. As several genetic mutations in the DNA repair genes are responsible of photo or radiosensitivity and high predisposition to cancers, we hypothesized that these effects in Gorlin syndrome might be due to a defect in the DNA damage response (DDR) and/or the DNA repair capacities. Therefore, the objective of this work was to investigate the sensitivity of skin fibroblasts from NBCCS patients to different DNA damaging agents and to determine the ability of these agents to modulate the DNA repair capacities. Gorlin fibroblasts showed high radiosensitivity and also less resistance to oxidative stress-inducing agents when compared to control fibroblasts obtained from healthy individuals. Gorlin fibroblasts harboring PTCH1 mutations were more sensitive to the exposure to ionizing radiation and to UVA. However, no difference in cell viability was shown after exposure to UVB or bleomycin. As BER is responsible for the repair of oxidative DNA damage, we decided to assess the BER pathway efficacy in Gorlin fibroblasts. Interestingly, a concomitant decrease of both BER gene expression and BER protein activity was observed in Gorlin fibroblasts when compared to control. Our results suggest that low levels of DNA repair within Gorlin cells may lead to an accumulation of oxidative DNA damage that could participate and partly explain the radiosensitivity and the BCC-prone phenotype in Gorlin syndrome.


[Study on sensitization and mechanism of CGA-BSA].
To investigate the sensitization and mechanism of artificial antigen of chlorogenic acid (CGA-BSA). Using intensive immunization to establish allergy animal model on guinea pig and preparing antiserum and tissue for further test. Using HE staining to observe pathology change of lungs, trachea, liver. Using passive mast cell (PMC) degranulation test to observe the immunogenicity of CGA-BSA and using ELISA to detect IgE and histamine in plasma. There established allergy animal model on guinea pig, which include a increase cell degranulation by a ratio (63.58 +/- 10.23)% in PMC test, increase of specific antibody IgE and increase of histamine in plasma after provocation by ELISA. Allergen CGA-BSA could provoke allergenic response in guinea pig, and the allergic response belongs to type I allergy.


Addressing Acute Stress among Professionals Caring for COVID-19 Patients: Lessons Learned during the First Outbreak in Spain (March-April 2020).
Objectives: To describe lessons learned during the first COVID-19 outbreak in developing urgent interventions to strengthen healthcare workers' capacity to cope with acute stress caused by health care pressure, concern about becoming infected, despair of witnessing patients' suffering, and critical decision-making requirements of the SARS-CoV-2 pandemic during the first outbreak in Spain. Methods: A task force integrated by healthcare professionals and academics was activated following the first observations of acute stress reactions starting to compromise the professionals' capacity for caring COVID-19 patients. Literature review and qualitative approach (consensus techniques) were applied. The target population included health professionals in primary care, hospitals, emergencies, and nursing homes. Interventions designed for addressing acute stress were agreed and disseminated. Findings: There are similarities in stressors to previous outbreaks, and the solutions devised then may work now. A set of issues, interventions to cope with, and their levels of evidence were defined. Issues and interventions were classified as: adequate communication initiative to strengthen work morale (avoiding information blackouts, uniformity of criteria, access to updated information, mentoring new professionals); resilience and recovery from physical and mental fatigue (briefings, protecting the family, regulated recovery time during the day, psychological first aid, humanizing care); reinforce leadership of intermediate commands (informative leadership, transparency, realism, and positive messages, the current state of emergency has not allowed for an empirical analysis of the effectiveness of proposed interventions. Sharing information to gauge expectations, listening to what professionals need, feeling protected from threats, organizational flexibility, encouraging teamwork, and leadership that promotes psychological safety have led to more positive responses. Attention to the needs of individuals must be combined with caring for the teams responsible for patient care. Conclusions: Although the COVID-19 pandemic has a more devastating effect than other recent outbreaks, there are common stressors and lessons learned in all of them that we must draw on to increase our capacity to respond to future healthcare crises.