Risk Factors and Outcomes in Dogs With Respiratory Disease Undergoing Diagnostic Airway Lavage.
Advanced diagnostic testing is becoming increasingly important to accurately assess pulmonary parenchymal, airway, and pulmonary vascular diseases in dogs. Due to respiratory system compromise, diagnostic procedures performed under general anesthesia, including thoracic computed tomography (CT) and bronchoalveolar lavage (BAL), are thought to carry significant risk to dogs with respiratory disease. In lieu of performing these diagnostics, empirical medical therapy is often administered, potentially delaying appropriate therapy or providing unnecessary treatment. This study prospectively evaluated risk factors and outcomes for dogs with respiratory disease undergoing general anesthesia for thoracic CT and BAL. Arterial blood gas samples were taken pre- and post-BAL to evaluate pulmonary gas exchange. Pre-BAL arterial partial pressure of oxygen-to-fractional inspired oxygen ratio was used to stratify dogs into groups of mild or moderate to severe disease severity. A novel thoracic CT disease severity scoring system was used to independently stratify dogs into mild or moderate to severe groups. Statistical comparisons between groups were made for signalment, body weight, temperature, pulse, respiratory rate, WBC count, ventilator-acquired pulmonary mechanics (specific compliance and resistance), change in arterial partial pressure of oxygen post-BAL, and outcomes. Seventeen dogs were prospectively enrolled. A comparatively lower heart rate at presentation was the only potential marker of increased disease severity identified when stratified by CT severity score. Arterial partial pressure of oxygen did not significantly decrease post-BAL regardless of disease severity or stratification method. The CT scoring system significantly correlated with the pre-BAL arterial partial pressure of oxygen-to-fractional inspired oxygen ratio. Incidence of post-procedural complications was 18%, with all complications being transient. Mortality as a direct complication of diagnostics was 0%. When considering euthanasia secondary to severity of the underlying disease and poor prognosis or death due to unrelated disease, mortality was 18%. In dogs with respiratory disease undergoing advanced diagnostic procedures, the overall incidence of post-procedural morbidity was low with no mortality directly attributed to the procedures. A novel CT disease severity scoring system was utilized and shows promise as a tool for evaluation of disease severity in this patient population when compared to arterial blood gas analysis.


Cardiovascular safety of sildenafil citrate (Viagra): an updated perspective.
Sildenafil citrate (Viagra; Pfizer Inc, New York, NY) relaxes vascular smooth muscle, resulting in modest reductions in blood pressure that are insufficient to stimulate a reflex increase in heart rate. These blood pressure reductions are similar for healthy men and men with coronary artery disease (CAD) or who use antihypertensive drugs. Sildenafil does not affect the force of cardiac contraction, and cardiac performance is unaffected. Sildenafil is mildly vasodilating in the coronary circulation and does not increase the risk of ventricular arrhythmia. During exercise and recovery, sildenafil does not cause clinically significant alterations in hemodynamic parameters in men with CAD, and it has no negative effects on coronary oxygen consumption, ischemia, or exercise capacity. Clinical trial data from >13,000 patients, 7 years of international postmarketing data, and observational studies of >28,000 men in the United Kingdom and 3813 men in the European Union reveal that (1) there are no special cardiovascular concerns when sildenafil is used in accordance with product labeling and (2) the risk for serious events such as myocardial infarction or death is not increased. However, because safety has not been established in patients with recent serious cardiovascular events, hypotension or uncontrolled hypertension, or retinitis pigmentosa, physicians should consult their current local prescribing information before prescribing sildenafil for these patients. Among men with erectile dysfunction treated with sildenafil, the adverse event profile is similar overall to that in men with comorbid cardiovascular disease (CVD), it is similar between those with and without CAD, and it is similar between those who take and those who do not take antihypertensive drugs (regardless of the number or class). In a controlled interaction study of sildenafil and amlodipine, the mean additional reduction in supine blood pressure was 8 mm Hg systolic and 7 mm Hg diastolic. Sildenafil should be used with caution in patients who take alpha-blockers because coadministration may lead to symptomatic hypotension in some individuals. When sildenafil is coadministered with an alpha-blocker, patients should be stable on alpha-blocker therapy before initiating sildenafil treatment and sildenafil should be initiated at the lowest dose. Also, in the absence of information specific to mixed alpha/beta blockers, such as carvedilol and labetalol, similar care should be taken as for alpha-blockers. Sildenafil potentiates the hypotensive effects of nitrates, and its administration to patients who are using organic nitrates in any form, either regularly or intermittently, is contraindicated. Before prescribing sildenafil, physicians should carefully consider whether their patients with underlying CVD could be affected adversely by resuming sexual activity. Management recommendations based on cardiovascular risk, from the Second Princeton Consensus Conference, are presented.


How can precision medicine be applied to temporomandibular disorders and its comorbidities?
The Eighth Scientific Meeting of The TMJ Association, Ltd. was held in Bethesda, Maryland, September 11-13, 2016. As in the past, the meeting was cosponsored by components of the National Institutes of Health with speakers invited to review the state of temporomandibular disorder science and propose recommendations to further progress. The theme of precision medicine, which aims to tailor disease treatment and prevention to match the characteristics of an individual patient (genetic, epigenetic, environmental, lifestyle) underscored the current consensus that temporomandibular disorders are no longer viewed as local conditions of jaw pain and dysfunction. Rather, they represent a complex family of biopsychosocial disorders that can progress to chronic pain, most often accompanied by one or more other chronic pain conditions. Temporomandibular disorders and these comorbidities, called chronic overlapping pain conditions, predominantly or exclusively affect women in their childbearing years and reflect central nervous system sensitization. Presenters at the meeting included leaders in temporomandibular disorder and pain research, temporomandibular disorder patients and advocates, and experts in other fields or in the use of technologies that could facilitate the development of precision medicine approaches in temporomandibular disorders.


Health-related quality of life measure distinguishes between low and high clinical T stages in esophageal cancer.
Functional Assessment of Cancer Therapy-Esophagus (FACT-E) is a health-related quality of life (HRQOL) instrument validated in patients with esophageal cancer. It is made up of both a general component and an esophageal cancer subscale (ECS). Our objective was to explore the relationship between baseline FACT-E, ECS and clinically determined T-stage in patients with stage II-IV cancer of the gastroesophageal junction or thoracic esophagus. Data from four prospective studies in Canadian academic hospitals were combined. These were consecutive and eligible patients treated between 1996 and 2014 with clinical stage II-IV cancer of the gastroesophageal junction or thoracic esophagus. All patients completed pre-treatment FACT-E. Parametric (ANOVA) and non-parametric (Kruskal-Wallis) analyses were performed. Of the 135 patients that were deemed eligible, the T-stage distribution determined clinically was: 10 (7.4%) T1, 33 (24.4%) T2, 79 (58.5%) T3 and 13 (9.6%) T4. Parametric analysis showed no significant association between FACT-E & T-stage, although there was a trend towards significance (P=0.08). Non-parametric analysis showed a significant association between FACT-E and T-stage (P=0.05). Post-hoc tests identified that the most significant differences in FACT-E scores were between T1 and T3 patients. Both parametric (P=0.002) and non-parametric (P=0.003) analyses showed an association between ECS & T-stage. Post-hoc analyses showed significant differences in ECS scores between T1 and higher T-stages (P<0.01). Patient-reported HRQOL scores appear to be significantly different in patients with clinical T1 esophageal cancer as compared to those with higher clinical T stages. Since distinguishing T1 from T2/T3 lesions is important in guiding the most appropriate treatment modality and since EUS appears to have difficulties reliably making such T-stage distinctions, FACT-E and ECS scores may be helpful as an adjunct to guide decision-making.


The Importance of Economic Perspective and Quantitative Approaches in Oncology Value Frameworks of Drug Selection and Shared Decision Making.
The debate around value in oncology drug selection has been prominent in recent years, and several professional bodies have furthered this debate by advocating for so-called value frameworks. Herein, we provide a viewpoint on these value frameworks, emphasizing the need to consider 4 key aspects: (1) the economic underpinnings of value; (2) the importance of the perspective adopted in the valuation; (3) the importance of the difference between absolute and relative measures of risk and measuring patient preferences; and (4) the recognition of multiple quality-of-life (QoL) domains, and the aggregation and valuation of those domains, through utilities within a multicriteria decision analysis, may allow prioritization of QoL above the tallying of safety events, particularly in a value framework focusing on the individual patient. While several frameworks exist, they incorporate different attributes and-importantly-assess value from alternative perspectives, including those of patients, regulators, payers, and society. The various perspectives necessarily lead to potentially different, if not sometimes divergent, conclusions about the valuation. We show that the perspective of the valuation affects the framing of the risk/benefit question and the methodology to measure the individual patient choice, or preference, as opposed to the collective, or population, choice. We focus specifically on the American Society of Clinical Oncology (ASCO) Value Framework. We argue that its laudable intent to assist in shared clinician-patient decision making can be augmented by more formally adopting methodology underpinned by micro- and health economic concepts, as well as application of formal quantitative approaches. Our recommendations for value frameworks focusing on the individual patient, such as the ASCO Value Framework, are 3-fold: (1) ensure that stakeholders understand the importance of the adopted (economic) perspective; (2) consider using exclusively absolute measures of risk and formal patient-preference methodology; and (3) consider foregoing safety parameters for higher-order utility considerations. No funding was received for conceptualizing, writing, and/or editing this manuscript. Waldeck and White are employees of, and received stock option grants from, Celldex Therapeutics. Van Hout and Botteman are employees and shareholders of Pharmerit International. Pharmerit International is a research contractor for Celldex. All authors have retained editorial control of the content of the manuscript. Conceptualization of this viewpoint article was contributed primarily by Waldeck, along with Botteman, White, and van Hout. Data analysis and revision of the manuscript was contributed equally by all the authors. The manuscript was written by Waldeck, Botteman, van Hout, and White.


When Veterinary Drugs Reach Human Hospitals: A Problem-Based Learning Discussion.
The delivery of drugs from the manufacturer to the hospital is a complex process. Despite numerous safeguards, lapses may occur, creating the potential for patient harm. Recently, an urban tertiary care medical center received a shipment of isoflurane bottles labeled for veterinary use. This error was not identified until the veterinary isoflurane reached the operating room automated medication dispensing system. No patients received the anesthetic. This report describes how such an error occurred, explains the differences between veterinary and human medications, and emphasizes the importance of vigilance in the drug supply chain to prevent patient harm.


Enhanced light absorption by mixed source black and brown carbon particles in UK winter.
Black carbon (BC) and light-absorbing organic carbon (brown carbon, BrC) play key roles in warming the atmosphere, but the magnitude of their effects remains highly uncertain. Theoretical modelling and laboratory experiments demonstrate that coatings on BC can enhance BC's light absorption, therefore many climate models simply assume enhanced BC absorption by a factor of ∼1.5. However, recent field observations show negligible absorption enhancement, implying models may overestimate BC's warming. Here we report direct evidence of substantial field-measured BC absorption enhancement, with the magnitude strongly depending on BC coating amount. Increases in BC coating result from a combination of changing sources and photochemical aging processes. When the influence of BrC is accounted for, observationally constrained model calculations of the BC absorption enhancement can be reconciled with the observations. We conclude that the influence of coatings on BC absorption should be treated as a source and regionally specific parameter in climate models.


Enhanced Binding Affinity via Destabilization of the Unbound State: A Millisecond Hydrogen-Deuterium Exchange Study of the Interaction between p53 and a Pleckstrin Homology Domain.
The incorporation of intrinsically disordered domains enables proteins to engage a wide variety of targets, with phosphorylation often modulating target specificity and affinity. Although phosphorylation can clearly act as a chemical driver of complexation in structured proteins, e.g., by abrogating or permitting new charge-charge interactions, the basis for enhancement of the hydrophobically driven interactions that are typical of disordered protein-target complexation is less clear. To determine how phosphorylation can positively impact target recruitment in disordered domains, we have examined the interaction between the disordered N-terminal transactivation domain (TAD) of p53 and the pleckstrin homology (PH) domain of p62. Using time-resolved electrospray ionization with hydrogen-deuterium exchange, we demonstrate that phosphorylation has little effect on the conformation of the p53 TAD when it is bound to the PH domain but instead increases the degree of conformational disorder in the unbound state. We propose that this increase in the degree of disorder creates a wider free energy gap between the free and bound states, providing a target-independent mechanism for enhanced binding when the phosphorylated and unphosphorylated p53-target complexes have similar free energies.


Mechanistic information on the reductive elimination from cationic trimethylplatinum(IV) complexes to form carbon-carbon bonds.
Cationic complexes of the type fac-[(L(2))Pt(IV)Me(3)(pyr-X)][OTf] (pyr-X = 4-substituted pyridines; L(2) = diphosphine, viz., dppe = bis(diphenylphosphino)ethane and dppbz = o-bis(diphenylphosphino)benzene; OTf = trifluoromethanesulfonate) undergo C-C reductive elimination reactions to form [L(2)Pt(II)Me(pyr-X)][OTf] and ethane. Detailed studies indicate that these reactions proceed by a two-step pathway, viz., initial reversible dissociation of the pyridine ligand from the cationic complex to generate a five-coordinate Pt(IV) intermediate, followed by irreversible concerted C-C bond formation. The reaction is inhibited by pyridine. The highly positive values for DeltaS()(obs) = +180 +/- 30 J K(-1) mol(-1), DeltaH(obs) = 160 +/- 10 kJ mol(-1), and DeltaV()(obs) = +16 +/- 1 cm(3) mol(-1) can be accounted for in terms of significant bond cleavage and/or partial reduction from Pt(IV) to Pt(II) in going from the ground to the transition state. These cationic complexes have provided the first opportunity to carry out detailed studies of C-C reductive elimination from cationic Pt(IV) complexes in a variety of solvents. The absence of a significant solvent effect for this reaction provides strong evidence that the C-C reductive coupling occurs from an unsaturated five-coordinate Pt(IV) intermediate rather than from a six-coordinate Pt(IV) solvento species.


The influence of positive end-expiratory pressure on surgical field conditions during functional endoscopic sinus surgery.
Functional endoscopic sinus surgery (FESS) is the mainstay of surgical treatment for sinonasal disease. This surgery carries certain risks. Most of these risks relate to the quality of the surgical field. Thus, mechanisms by which the surgical field can be improved are important to study. We sought to determine whether positive end-expiratory pressure (PEEP) had a deleterious effect on the quality of the surgical field in patients undergoing primary FESS. Forty-seven patients were randomized to a ventilation strategy using either 5 cm H2O of PEEP or zero added PEEP. The quality of the surgical field was measured every 15 minutes using a validated surgical scoring method. The addition of PEEP did not have any measurable effect on the surgical field scores after onset of surgery (odds ratio [OR] (95% confidence interval [CI]) = 1.06 (0.44-2.58), P = 0.895 for side 1; OR (95% CI) = 0.56 (0.16-1.93), P = 0.356 for side 2). The peak inspiratory pressure did have an effect on surgical grades. Every cm H2O of added pressure over 15 cm H2O total pressure contributing to increased odds of higher surgical field score. For each cm H2O increase in inspiratory pressure above 15cm H2O increased the surgical field score (OR [95% CI] 1.13 [1.04-1.22], P = 0.002). During FESS surgery if PEEP is added, it is important to keep the mean inspiratory pressure below 15cm H2O to avoid worsening surgical field conditions.


The opgGIH and opgC genes of Rhodobacter sphaeroides form an operon that controls backbone synthesis and succinylation of osmoregulated periplasmic glucans.
Osmoregulated periplasmic glucans (OPGs) of Rhodobacter sphaeroides are anionic cyclic molecules that accumulate in large amounts in the periplasmic space in response to low osmolarity of the medium. Their anionic character is provided by the substitution of the glucosidic backbone by succinyl residues. A wild-type strain was subject to transposon mutagenesis, and putative mutant clones were screened for changes in OPGs by thin layer chromatography. One mutant deficient in succinyl substitution of the OPGs was obtained and the gene inactivated in this mutant was characterized and named opgC. opgC is located downstream of three ORFs, opgGIH, two of which are similar to the Escherichia coli operon, mdoGH, governing OPG backbone synthesis. Inactivation of opgG, opgI or opgH abolished OPG production and complementation analysis indicated that the three genes are necessary for backbone synthesis. In contrast, inactivation of a gene similar to ndvB, encoding the OPG-glucosyl transferase in Sinorhizobium meliloti, had no consequence on OPG synthesis in Rhodobacter sphaeroides. Cassette insertions in opgH had a polar effect on glucan substitution, indicating that opgC is in the same transcription unit. Expression of opgIHC in E. coli mdoB/mdoC and mdoH mutants allowed the production of slightly anionic and abnormally long linear glucans.


Development of a Scalable Process for the Synthesis of DNDI-VL-2098: A Potential Preclinical Drug Candidate for the Treatment of Visceral Leishmaniasis.
A process suitable for kilogram-scale synthesis of (2R)-2-methyl-6-nitro-2-{[4-(trifluoromethoxy)phenoxy]methyl}-2,3-dihydroimidazo[2,1-b][1,3]oxazole (DNDI-VL-2098, 2), a preclinical drug candidate for the treatment of visceral leishmaniasis, is described. The four-step synthesis of the target compound involves the Sharpless asymmetric epoxidation of 2-methyl-2-propen-1-ol, 8. Identification of a suitable synthetic route using retrosynthetic analysis and development of a scalable process to access several kilograms of 2 are illustrated. The process was simplified by employing in situ synthesis of some intermediates, reducing safety hazards, and eliminating the need for column chromatography. The improved reactions were carried out on the kilogram scale to produce 2 in good yield, high optical purity, and high quality.


Platelet-derived growth factor-stimulated c-myc RNA accumulation in MG-63 human osteosarcoma cells is independent of both protein kinase A and protein kinase C.
Treatment of quiescent MG-63 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) or platelet-derived growth factor (PDGF) stimulates the rapid accumulation of c-myc RNA. We have now determined that a similar effect can be induced by cAMP. Treatment with forskolin (an activator of adenylate cyclase), IBMX (a phosphodiesterase inhibitor), PGE1, and isoproterenol stimulated accumulation of both cAMP and c-myc RNA, but no increase in either cAMP or c-myc RNA was seen with the inactive forskolin analog 1,9-dideoxyforskolin. Forskolin and IBMX acted synergistically in stimulating accumulation of both cAMP and c-myc RNA. However, three lines of evidence indicated that PDGF action is not mediated by cAMP. First, PDGF treatment caused no elevation of cAMP within 1 h, even in the presence of IBMX. Second, the kinetics of c-myc RNA elevation after treatment with PDGF or forskolin were similar, ruling out delayed onset of cAMP stimulation. Finally, simultaneous treatment with forskolin and the calcium ionophore A23187 enhanced the elevation of c-myc RNA levels; no such effect was seen with PDGF. We had previously shown that PDGF action is not affected by prior treatment of MG-63 cells with TPA, a treatment which desensitizes the c-myc response to TPA. Similarly, TPA pretreatment had minimal effect on forskolin or IBMX-induced c-myc expression. These data suggest that cAMP, phorbol esters, and PDGF act independently to stimulate c-myc RNA expression in MG-63 cells. However, nuclear runoff experiments and RNA half-life measurements demonstrated that PDGF, phorbol ester, and cAMP all act to increase the transcription of the MYC gene.


Alois Alzheimer on presenile dementia.
The work of Alois Alzheimer on presenile dementia is a landmark in the history of psychiatry not fully appreciated by contemporary psychiatrists. In this paper, the history of his landmark work is reviewed in the context of the growing importance of psychiatric involvement in Alzheimer's disease. Annotated excerpts from Alzheimer's second paper (1911), never before translated into English, are presented. The historical significance of Alzheimer's findings vis-a-vis Kraepelinian psychiatry and the relationship of his investigations to modern psychiatric research in primary degenerative dementia of the Alzheimer type are discussed.


Early surgical outcomes of NiTi endoluminal compression anastomotic clip (NiTi CAC 30) use in patients with gastrointestinal malignancy.
The NiTi endoluminal Compression Anastomotic Clip (CAC™) 30 (NiTi CAC 30) (NiTi Alloys Technologies, Ltd., Netanya, Israel) is a new device with shape-memory characteristics. We aimed to investigate the safety and early surgical outcomes of NiTi CAC 30 for intestinal anastomosis in patients with gastrointestinal malignancy. Fifty patients operated on with NiTi CAC 30 were matched for sex, age, body mass index, operation type (open versus laparoscopy), operation name, and anastomosis type with patients in a control group operated on with a stapling device between November 2009 and May 2010. Early clinical outcomes were investigated. One misfired case of NiTi CAC 30 was excluded. Between the two groups, no significant differences were observed in demographics except for previous abdominal operation history. The results of early clinical outcomes were investigated, including operation time, estimated blood loss, time to first flatus, first defecation, and discharge, and complications. No differences were noted. Postoperatively, migration started in 1 patient between 3 and 5 days, 11 patients between 6 to 7 days, and 37 patients after 8 days. The expulsion of 31 cases occurred between 2 and 3 weeks, postoperatively. The NiTi CAC 30 was expulsed within 1 week in 4 patients and between 1 to 2 weeks in 8 patients. An expulsion occurred in 1 case at over 4 weeks. No problems related to early migration and expulsion were observed, and no anastomotic leakage and bleeding occurred. Intestinal anastomosis with the NiTi CAC 30 was safe and feasible without anastomotic leakage and reoperation compared with the stapling technique.


An in silico Framework of Cartilage Degeneration That Integrates Fibril Reorientation and Degradation Along With Altered Hydration and Fixed Charge Density Loss.
Injurious mechanical loading of articular cartilage and associated lesions compromise the mechanical and structural integrity of joints and contribute to the onset and progression of cartilage degeneration leading to osteoarthritis (OA). Despite extensive in vitro and in vivo research, it remains unclear how the changes in cartilage composition and structure that occur during cartilage degeneration after injury, interact. Recently, in silico techniques provide a unique integrated platform to investigate the causal mechanisms by which the local mechanical environment of injured cartilage drives cartilage degeneration. Here, we introduce a novel integrated Cartilage Adaptive REorientation Degeneration (CARED) algorithm to predict the interaction between degenerative variations in main cartilage constituents, namely collagen fibril disorganization and degradation, proteoglycan (PG) loss, and change in water content. The algorithm iteratively interacts with a finite element (FE) model of a cartilage explant, with and without variable depth to full-thickness defects. In these FE models, intact and injured explants were subjected to normal (2 MPa unconfined compression in 0.1 s) and injurious mechanical loading (4 MPa unconfined compression in 0.1 s). Depending on the mechanical response of the FE model, the collagen fibril orientation and density, PG and water content were iteratively updated. In the CARED model, fixed charge density (FCD) loss and increased water content were related to decrease in PG content. Our model predictions were consistent with earlier experimental studies. In the intact explant model, minimal degenerative changes were observed under normal loading, while the injurious loading caused a reorientation of collagen fibrils toward the direction perpendicular to the surface, intense collagen degradation at the surface, and intense PG loss in the superficial and middle zones. In the injured explant models, normal loading induced intense collagen degradation, collagen reorientation, and PG depletion both on the surface and around the lesion. Our results confirm that the cartilage lesion depth is a crucial parameter affecting tissue degeneration, even under physiological loading conditions. The results suggest that potential fibril reorientation might prevent or slow down fibril degradation under conditions in which the tissue mechanical homeostasis is perturbed like the presence of defects or injurious loading.


Amyloid burden in cognitively normal elderly is associated with preferential hippocampal subfield volume loss.
The earliest sites of brain atrophy in Alzheimer's disease are in the medial temporal lobe, following widespread cerebral cortical amyloid deposition. We assessed 74 cognitively normal participants with clinical measurements, amyloid-β-PET imaging, MRI, and a newly developed technique for MRI-based hippocampal subfield segmentation to determine the differential association of amyloid deposition and hippocampal subfield volume. Compared to amyloid-negative participants, amyloid-positive participants had significantly smaller hippocampal tail, presubiculum, subiculum, and total hippocampal gray matter volumes. We conclude that, prior to the development of cognitive impairment, atrophy in particular hippocampal subfields occurs preferentially with amyloid-β accumulation.


Epidermoid Cyst of the Ear Lobule in Adult.
An epidermoid cyst is one of the most common benign cysts of the skin. The cyst is filled with keratin flakes and its wall is composed of keratinized, stratified, squamous epithelium. Epidermoid cysts can occur anywhere on the body, usually along the lines of embryonic fusion and mostly on the face, scalp, neck, chest, and upper back. Around 80% of the epidermoid cysts are seen in ovaries and testicles whereas, in the head and neck, they account for only about 7% and 1.6% of epidermoid cysts are reported in the oral cavity. The condition can be congenital or acquired. Congenital causes are rare and may be caused by the entrapment of ectodermal elements intradermally or subcutaneously during embryogenesis. Acquired causes of an epidermoid cyst may result from traumatic or iatrogenic implantation of epithelial cells into the dermal layer or from obstruction of a pilosebaceous unit in the hair follicle. Surgical excision completes the treatment.


Workforce reentry for people with HIV/AIDS: intervention effects and predictors of success.
Treatment that prolongs the lives of people with HIV/AIDS and improves their quality of life is relatively recent and little is known about factors that may predict their successful re-entry to the workforce. No data exist concerning the effectiveness of programs to assist people with HIV/AIDS in their efforts to return to work. We used logistic regression and Kaplan-Meier survival curves to predict return to work using data from 126 individuals who participated in an HIV/AIDS return to work program. Results from the 24 month follow-up revealed that program participation, general health, benefits status, and gender, predicted successful re-entry to the workforce. We discuss these findings in the context of the need for more explicitly-defined interventions, as well as the need for additional information on factors that may hinder or facilitate workforce re-entry among people with HIV/AIDS.


Uric acid lithiasis in the Sudan.
Fifty-seven per cent of Urinary Calculi in the Sudan contain Uric Acid, 20 per cent in the pure form and 37 per cent mixed with other constituents mainly calcium oxalate. The peak age presentation of urolithiasis is 30-40 years with more prediliction to males than females. An earlier study documented a high incidence of hyperuricaemia in Sudanese people. It is probable that "voluntary dehydration" and hyperuricaemia acting together may help in the formation of uric acid stones on the surface of which other crystals mainly calcium oxalate may be deposited to form the bigger calculi which are commonly encountered in this country.


[Prokaryotic expression of DNA recombinase FLP and its purification with enzymatic activity].
DNA recombinase FLP gene exists on the 2 micro plasmid of Saccharomyces cerevisiae. Recombinase FLP could recognize an FRT site composed of 34bp and function the sequences for exchange, recombination, deletion and reversion between the two orientated FRT sites. These functions are highly recognized by molecular biologists and biotechnology engineers for theoretic and applicable technology studies. This work constructed a prokaryotic over-expressed vector harboring FLP gene nominated as pQE30-flpe and established its over-expression culture system in which recombinase FLP could be efficiently expressed in E. coli strain M15. Purification procedures for high purity and active FLP are established through combination of ammonium sulfate precipitation with a 0.5-1.0 mL micro-column technique of Ni affinity chromatography with gradient elution. To verify the recombinase activity of purified FLP, substrate vectors, sequence donor vector (pUC18-FRT-gfp-FRT) and sequence accepting vector (pET30a-FRT) are constructed with various number, orientation of FRTs harboring the GFP gene for the expression of visible assay of the functions of recombination, exchange and deletion. Results showed that the system not only over expressed recombinase FLP in prokaryotic E. coli, but also efficiently purified the enzyme with a higher activity of the function of recombination, exchange and deletion. The system and the method are easily implemented and feasibly manipulated for theoretic study and biotechnology application.


Region-specific expression of androgen and growth factor pathway genes in the rat epididymis and the effects of dual 5alpha-reductase inhibition.
Dihydrotestosterone (DHT) is the primary androgen acting in the epididymis, the site of sperm maturation. Previously, we showed that the treatment of male rats with PNU157706, an inhibitor that acts on both isoforms of 5alpha-reductase to prevent DHT formation, has effects on the expression of genes implicated in processes that create the optimal luminal microenvironment required for sperm maturation, and on sperm maturation itself. However, signaling pathways involved in regulating or mediating DHT actions in the epididymis remain largely unknown. The goals of this study were to determine the expression profiles of potential signaling systems in the epididymis and assess their DHT-dependence using two different dual 5alpha-reductase inhibitors. Rats were untreated or gavaged with vehicle, 10 mg/kg per day PNU157706 or 32 mg/kg per day FK143 for 28 days and epididymal gene expression was analyzed. Gene array analysis revealed analogous effects of FK143 on overall epididymal gene expression when compared with previous PNU157706 studies. Quantitative RT-PCR analysis of the expression of the 5alpha-reductase isozymes, androgen receptor, and members of the IGF, FGF, TGF, and VEGF families revealed novel region-specific expression profiles in the epididymis that were differentially affected by 5alpha-reductase inhibition; the two inhibitors had parallel effects. Specifically, in proximal regions, 5alpha-reductase 1, androgen receptor, and TGF-beta1 expression increased after treatment, while in distal regions expression of IGF-I, IGFBP-5, IGFBP-6, and FGF-10 decreased. These results provide insight into epididymal signaling mechanisms and indicate potential candidates acting either upstream or downstream of DHT to regulate and/or mediate its actions in the epididymis.


Triggering Magnets for Wiegand Sensors: Electrodeposited and Origami-Magnetized CoNiP Micro-Magnets.
Miniature sensors are key components for applications in the Internet of Things (IoT), wireless sensor networks, autonomous vehicles, smart cities, and smart manufacturing. As a miniature and self-powered magnetic sensor, the Wiegand sensor possesses advantageous traits including changing-rate-independent output, low cost, and remarkable repeatability and reliability. A typical Wiegand sensor requires hard magnetic pole pieces that provide external fields for triggering voltage outputs that are called Wiegand pulses. However, the wire-shaped sensing element of Wiegand sensors is the critical issue that limits the design, selection, and adoption of the external triggering magnets. Currently, the widely used pole piece materials are rare-earth magnets. However, adopting rare-earth magnets brings strong stray fields, causing an electromagnetic interference (EMI) problem. In this study, patterned CoNiP hard magnets were electrodeposited on flexible substrates through microfabrication. Origami magnetization was utilized to control the resultant stray fields and thus the pole piece of CoNiP magnets can successfully trigger the output of the Wiegand pulse. In comparison, the output voltage of the triggered pulse acquired through the patterned CoNiP magnets is comparable to that acquired by using the rare-earth magnets. Furthermore, both the volume (and hence the weight) of the Wiegand sensor and the EMI issue can be significantly reduced and mitigated, respectively, by the CoNiP magnets.


[Intestinal digeneans of birds (superfamily Diplostomoidea) of the masurian lakes].
The aim of this study was to complete the information on digenean fauna of birds on the basis of the collection of diplostomid digeneans gathered in 1994-1970 during the field investigations directed by prof. Wiśniewski in the region of Masurian lakeland. A total number of 742 birds from the lakes: Gołdapiwo, Mamry Północne, Swiecajty and Dargin, belonging to 27 species (8 families) were examined. 335 specimens (45.1%) of infected bird hosted 30 species of intestinal digeneans belonging to the family Diplostomidae (Codonocephalus urniger, Conodiplostomum spathula, Diplostomum baeri, D. commutatum, D. pseudospathaceum, D. spathaceum, Hysteromorpha triloba, Neodiplostomum spathoides, Posthodiplostomum brevicaudatum, P. cuticola, Posthodiplostomum sp., Tylodelphys clavata, T. excavata, T. podicipina), Cyathocotylidae (Cyathocotyle prussica, Holostephanus dubinini, Paracoenogonimus ovatus) and Strigeidae (Apatemon gracilis, Apharyngostrigea cornu, Australapatemon minor, Cotylurus brevis, C. cornutus, C. hebraicus, C. raabei, Ichthyocotylurus erraticus, I. pileatus, I. platycephalus, Ophiosoma patagiatum, Parastrigea flexilis, Strigea falconis). Their specificity and frequency (prevalence, mean intensity and abundance), as well as domination status of these species are also discussed. Cotylurus brevis Dubois et Rausch, 1950 is recorded for the first time in Poland.


Elucidation of the Metabolic Network of Helicobacter pylori J99 and Malaysian Clinical Strains by Phenotype Microarray.
Helicobacter pylori colonizes almost half of the human population worldwide. H. pylori strains are genetically diverse, and the specific genotypes are associated with various clinical manifestations including gastric adenocarcinoma, peptic ulcer disease (PUD), and nonulcer dyspepsia (NUD). However, our current knowledge of the H. pylori metabolism is limited. To understand the metabolic differences among H. pylori strains, we investigated four Malaysian H. pylori clinical strains, which had been previously sequenced, and a standard strain, H. pylori J99, at the phenotypic level. The phenotypes of the H. pylori strains were profiled using the Biolog Phenotype Microarray system to corroborate genomic data. We initiated the analyses by predicting carbon and nitrogen metabolic pathways from the H. pylori genomic data from the KEGG database. Biolog PM aided the validation of the prediction and provided a more intensive analysis of the H. pylori phenomes. We have identified a core set of metabolic nutrient sources that was utilized by all strains tested and another set that was differentially utilized by only the local strains. Pentose sugars are the preferred carbon nutrients utilized by H. pylori. The amino acids l-aspartic acid, d-alanine, and l-asparagine serve as both carbon and nitrogen sources in the metabolism of the bacterium. The phenotypic profile based on this study provides a better understanding on the survival of H. pylori in its natural host. Our data serve as a foundation for future challenges in correlating interstrain metabolic differences in H. pylori.


Use of chitosan wound dressing for the treatment of surgical site infection: a case report.
Surgical site infections (SSIs) are treated using topical antiseptics and systemic antibiotics, but some cases are unresponsive to such regimens. This case study reports the effective healing of an SSI by a chitosan wound dressing (MaxioCel; Axio Biosolutions Private Limited, India) in a 63-year-old female patient. The patient presented with an infected, hard-to-heal wound in the abdominal region, developed after a hernia surgery, and was initially treated with standard procedures. However, due to the continuous progression of infection, a highly absorbent, bioactive microfibre dressing was selected for the treatment and was continued for two months with alternate-day dressing changes. After 60 days of treatment, wound healing was observed, along with remission from the infection, as well as reduction in exudate level and pain. The use of chitosan wound dressing in management of hard-to-heal infected wounds provides efficient remission of SSI and a faster healing rate.


Functional characterization of squalene synthase and squalene epoxidase in Taraxacum koksaghyz.
The Russian dandelion Taraxacum koksaghyz produces high-value isoprenoids such as pentacyclic triterpenes and natural rubber in the latex of specialized cells known as laticifers. Squalene synthase (SQS) and squalene epoxidase (SQE) catalyze key steps in the biosynthesis of cyclic terpenoids, but neither enzyme has yet been characterized in T. koksaghyz. Genomic analysis revealed the presence of two genes (TkSQS1 and TkSQS2) encoding isoforms of SQS, and four genes (TkSQE1-4) encoding isoforms of SQE. Spatial expression analysis in different T. koksaghyz tissues confirmed that TkSQS1 and TkSQE1 are the latex-predominant isoforms, with highly similar mRNA expression profiles. The TkSQS1 and TkSQE1 proteins colocalized in the endoplasmic reticulum membrane and their enzymatic functions were confirmed by in vitro activity assays and yeast complementation studies, respectively. The functions of TkSQS1 and TkSQE1 were further characterized in the latex of T. koksaghyz plants with depleted TkSQS1 or TkSQE1 mRNA levels, produced by RNA interference. Comprehensive expression analysis revealed the coregulation of TkSQS1 and TkSQE1, along with a downstream gene in the triterpene biosynthesis pathway encoding the oxidosqualene cyclase TkOSC1. This indicates that the coregulation of TkSQS1, TkSQE1, and TkOSC1 could be used to optimize the flux toward specific terpenoids during development.


Consensus report on acoustic rhinometry and rhinomanometry.
With respect to acoustic rhinometry, new elements concern the problems related to the interpretation of the minimal cross-sectional area, and the presentation of a protocol for a multinational study, which aims to define a normal nose. Also, the previously issued recommendations for standardisation for technical specifications and standard operating procedures are briefly reviewed. For rhinomanometry, new insights into the field of fluid dynamics are highlighted, as well as their repercussion on more recent graphical representations for active anterior rhinomanometry such as four phases rhinomanometry and resistometry. For acoustic rhinometry as well as rhinomanometry, a more stringent standardisation of decongestive procedures is suggested.


[International and regional standardization of immunoenzyme tests: methods, concerns and limitations].
Numerous attempts have been made to standardise immuno-enzyme techniques (enzyme-linked immunosorbent assay: ELISA) used for the diagnosis of infectious diseases, in order to improve the reproducibility of the tests, expression of results, choice of a positive threshold, and selection of reference samples. The international standardisation of reagents and test protocols appears essential for quality control and the comparison of results between laboratories, but the interpretation of results can encounter major differences depending on the geographical sector under study. Based on these studies, and in the light of a model indirect ELISA for detecting antibodies against Trypanosoma vivax in cattle, the author proposes the international standardisation of reagents, test protocol, and the expression of results of ELISA using international reference samples. For local standardisation, the following proposals are made: sampling of representative local populations. Establishment of the distribution patterns of infected and uninfected local populations. Selection of representative controls from local populations (secondary reference samples). Expression of test results in comparison with these controls. Establishment of internal quality control based on the response of controls. Determination of a positive threshold, in accordance with the requirements of the user. Adaptation of the positive threshold according to the prevalence observed in the geographical sector under study.


Anterolateral Extraarticular Stabilisation of the Knee: Modified Lemaire Procedure.
The anterolateral aspect of the knee is prone to laxity or symptomatic instability, if the anterior cruciate ligament (ACL) is torn. It is necessary to address this issue in patients with general joint hyperlaxity, overextension of the knee, massive anterolateral instability, or re-tear of the ACL with chronic instability. In these cases, and in addition to a preoperative bony workup and revision ACL reconstruction, anterolateral stabilisation should be considered to avoid persistent anterolateral rotation instability and failure of the ACL reconstruction.To stabilise the anterolateral corner of the knee, the modified Lemaire procedure as presented and illustrated here is a straight forward surgical technique that can be performed right after standard ACL reconstruction surgery, if indicated. It is independent from the graft choice for the ACL reconstruction, and the surgical setting in the operating room remains unchanged.


[Tissue antioxidant capacity and bacterial translocation in parenteral nutrition. Experimental study].
Alterations in the antioxidant system (AS) has been observed during total parenteral nutrition (TPN). Light exposure or changes in the composition of TPN may affect this deleterious effect. On the other hand, bacterial translocation (BT) is frequent under TPN and may be related to AS. The aim of the study was to determine the adverse effect of standard and glutamine-enriched (GE) TPN, with or without light exposure, on the AS, and its relationship to BT. Forty-nine adult Wistar rats underwent central venous cannulation and were randomly assigned to one of five groups: Sham (n = 16): chow and water ad libitum and saline i.v. TPN (n = 10): had standard TPN. TPN(-) (n = 8): standard TPN without light-exposure. GTPN (n = 8): GE TPN. GTPN(-) (n = 7): GE TPN without light exposure. After 10 days, glutation reduced (GSH) was determined in liver and kidney. Mesenteric lymph nodes, peripheral and portal blood samples were cultured for BT. Comparing to Sham rats, TPN groups had statistically significant lower GSH levels, but there were no differences between standard or GE groups nor with or without light exposure groups. Sham animals had 12% BT. Significantly higher BT (p < 0.05) was found in TPN rats: 70% in TPN group, 88% in TPN(-) group, 86% in GTPN(-) animals and only 50% in GTPN group (p = 0.06 vs TPN group). To conclude: 1. TPN reduces antioxidant capacity and induces BT. 2. Glutamine supplementation or light protection do not improve tissue antioxidant capacity under TPN. 3. Glutamine supplementation tends to reduce BT only in the presence of light. 4. Absence of light exposure does not improve BT TPN-related.


Liver stiffness is able to differentiate hepatosplenic Schistosomiasis mansoni from liver cirrhosis and spleen stiffness may be a predictor of variceal bleeding in hepatosplenic schistosomiasis.
Ultrasonography is limited for differentiating portal hypertension due to liver cirrhosis from that secondary to hepatosplenic schistosomiasis (HSS). We aimed to investigate the role of transient elastography (TE) in differentiating HSS mansoni from cirrhosis and the factors associated with liver and spleen stiffness (LS and SS) in HSS. A cross-sectional study was conducted including patients with HSS mansoni (n=29) and liver cirrhosis due to non-alcoholic steatohepatitis (n=23). All patients underwent TE and those with HSS were assessed by the Niamey protocol. HSS subjects presented lower median LS (9.6 vs 21.3 Kpa, p<0.001) and liver controlled attenuation parameter (229 vs 274 dB/m, p=0.010) than cirrhosis subjects, in addition to higher SS (73.5 vs 42.2 Kpa, p=0.002). The area under the receiver operating characteristic curve for detecting cirrhosis by LS was 0.947 (95% CI 0.89 to 1.00, p<0.001), with an optimal cut-off of 11.75 Kpa. In HSS subjects, higher SS was associated with the presence of the following: diabetes mellitus (p=0.036), metabolic syndrome (p=0.043), esophageal varices (p=0.001), portal vein thrombosis (p=0.047) and previous variceal bleeding (p=0.011). In HSS patients without portal vein thrombosis, variceal bleeding was associated with higher SS (p=0.018). Niamey categories were not associated with LS (p=0.676) or SS (p=0.504). TE can play a role in differentiating HSS from cirrhosis, especially by LS. SS may be further investigated for predicting complications in HSS.


Will Fluoroscopic Follow-up after Stent-Assisted Coiling of Cerebral Aneurysms Provide Information on Recanalization?
Fluoroscopic images for comparison (FICs) can be easily obtained for follow-up on an outpatient basis. This study retrospectively assessed the diagnostic performance of a set of FICs for evaluation of recanalization after stent-assisted coiling, with digital subtraction angiography (DSA) as the reference standard. A total of 124 patients harboring 144 stent-assisted coiled aneurysms were included. At least one month postembolization they underwent follow-up angiograms comprising a routine frontal and lateral DSA and a working-angle DSA. For analysis, FICs should be compared with the mask images of postprocedural DSAs to find recanalization. Instead of FIC acquisition, the mask images of follow-up DSAs were taken as a substitute because of the same view-making processes as FICs, full availability, and perfect coincidence with follow-up DSAs. Two independent readers evaluated a set of 169 FICs and DSA images for the presence of recanalization one month apart. Sensitivity, specificity, and interreader agreement were determined. Recanalization occurred in 24 (14.2%) cases. Of these, nine (5.3%) cases were found to have significant recanalization in need of retreatment. Sensitivity and specificity rates were 79.2% (19 of 24) and 95.9% (139 of 145) respectively for reader 1, and 66.7% (16 of 24) and 97.9% (142 of 145) for reader 2. Minimal recanalization was identified in seven out of all eight false negative cases. Excluding minimally recanalized cases in no need for retreatment from the recanalization group, calculation resulted in high sensitivity and specificity of over 94% for both readers. Interreader agreement between the two readers was excellent (96.4%; κ = 0.84). FICs may be a good imaging modality to detect significant recanalization of stent-assisted coiled aneurysms.


Child understandings of the causation of childhood burn injuries: Child activity, parental domestic demands, and impoverished settings.
Burns are a global public health problem. In South Africa, the rate of paediatric burn deaths is 5 times higher than other upper middle-income countries, with concentrations in impoverished settings. Globally, the majority of research focuses on expert and caregiver descriptions of burn occurrence, causation, and prevention, with limited consideration of children's perspectives. This study investigated children's understanding of the causation and prevention of childhood burns. Data were collected from eighteen 10- to 11-year-old children living in selected impoverished, fire-affected neighbourhoods in Cape Town, through 3 isiXhosa focus groups. All focus groups were transcribed, coded, and analysed for emerging themes through thematic analysis. Themes regarding burn causation and risks centred around 4 themes: (a) developmental limits in context; (b) domestic chores, child capacity, and inability to say "no"; (c) inadequate supervision and compromised caregiving; and (d) unsafe structures. Child accounts of prevention pertained to (e) burn injury prevention activities in comprised environments and emphasized child agency, and upgrading the physical environment. The children in this study ascribed burn injuries as the consequence of their developmental limits in the context of poverty, constraints on parental supervision, and unsafe environments. The children recommended safety education and upgrading their physical environments as part of burns injury prevention. The child accounts offer useful insights to inform safety interventions in impoverished settings.


Tropolone-Bearing Sesquiterpenes from Juniperus chinensis: Structures, Photochemistry and Bioactivity.
The tropolone-bearing sesquiterpenes juniperone A (1) and norjuniperone A (2) were isolated from the folk medicinal plant Juniperus chinensis, and their structures were determined by a combination of spectroscopic and crystallographic methods. Photojuniperones A1 (3) and A2 (4), bearing bicyclo[3,2,0]heptadienones derived from tropolone, were photochemically produced and structurally identified by spectroscopic methods. Predicted by the machine learning-based assay, 1 significantly inhibited the action of tyrosinase. The new compounds also inhibited lipid accumulation and enhanced the extracellular glycerol excretion.


Replacing -CH2CH2- with -CONH- does not significantly change rates of charge transport through Ag(TS)-SAM//Ga2O3/EGaIn junctions.
This paper describes physical-organic studies of charge transport by tunneling through self-assembled monolayers (SAMs), based on systematic variations of the structure of the molecules constituting the SAM. Replacing a -CH(2)CH(2)- group with a -CONH- group changes the dipole moment and polarizability of a portion of the molecule and has, in principle, the potential to change the rate of charge transport through the SAM. In practice, this substitution produces no significant change in the rate of charge transport across junctions of the structure Ag(TS)-S(CH(2))(m)X(CH(2))(n)H//Ga(2)O(3)/EGaIn (TS = template stripped, X = -CH(2)CH(2)- or -CONH-, and EGaIn = eutectic alloy of gallium and indium). Incorporation of the amide group does, however, increase the yields of working (non-shorting) junctions (when compared to n-alkanethiolates of the same length). These results suggest that synthetic schemes that combine a thiol group on one end of a molecule with a group, R, to be tested, on the other (e.g., HS~CONH~R) using an amide-based coupling provide practical routes to molecules useful in studies of molecular electronics.


HSP20 Exerts a Protective Effect on Preeclampsia by Regulating Function of Trophoblast Cells Via Akt Pathways.
Preeclampsia (PE) remains the leading cause of maternal and fetal morbidity and mortality. Excessive apoptosis of the placenta and poor remodeling of spiral arteries caused by insufficient invasion of trophoblast cells into uterus have been implicated in the pathogenesis of PE. Accumulating evidence showed that heat shock protein 20 (HSP20) is closely associated with the proliferation, apoptosis, and metastasis of tumor cells. However, little is known about whether HSP20 plays a role in the development of PE. In this study, we detected the apoptosis index and the expressions of HSP20 and apoptosis-associated proteins in the placentas from PE and normal pregnancies. We found that HSP20 was reversely related to the apoptosis rate and the levels of proapoptotic proteins. Moreover, we identified that HSP20 could suppress the proliferation and apoptosis of trophoblast cells, turning them into a more invasive phenotype. Additionally, H2O2-induced oxidative stress was significantly alleviated, and several key proteins on the Akt signaling pathway were upregulated in HSP20-overexpressing trophoblast cells. These findings strongly suggested that HSP20 might play a role in the remodeling of spiral arteries through affecting the invasiveness of extravillous trophoblast cells via Akt signaling pathway, and the dysregulation of it might contribute to the pathophysiology of PE.


Management of a Rare Complication of Epidural Analgesia in an Obese Laterally Positioned Parturient: Catheter Entrapment Next to the Inferior Vena Cava.
Intravascular, subdural, intrathecal, and subcutaneous placement of epidural catheters are known complications and common causes of anesthesia and analgesia failure. Because the epidural space is located near the retroperitoneum and catheters are placed blindly, it is possible that misplacement could involve other structures, including the inferior vena cava, the aorta, and the lumbar plexus. We report a case of an obese laterally positioned parturient who presented with an epidural catheter lodged in the retroperitoneum. The catheter provided inadequate analgesia for labor, and postpartum computed tomography revealed it to be located in the retroperitoneal space just adjacent to the inferior vena cava. Conventional removal techniques were unsuccessful, and the catheter was finally removed after insertion of a guide wire under fluoroscopy. We conclude that obesity and lateral positioning are factors that increase the risk of epidural catheter misplacement, and a large distance from skin to loss of resistance is a potential sign of misplacement. We recommend ultrasound imaging to aid in the insertion of epidural catheters in high-risk patients.


Recent changes in therapeutic approaches and association with outcomes among patients with secondary hyperparathyroidism on chronic hemodialysis: the DOPPS study.
Elevated parathyroid hormone levels may be associated with adverse clinical outcomes in patients on dialysis. After the introduction of practice guidelines suggesting higher parathyroid hormone targets than those previously recommended, changes in parathyroid hormone levels and treatment regimens over time have not been well documented. Using data from the international Dialysis Outcomes and Practice Patterns Study, trends in parathyroid hormone levels and secondary hyperparathyroidism therapies over the past 15 years and the associations between parathyroid hormone and clinical outcomes are reported; 35,655 participants from the Dialysis Outcomes and Practice Patterns Study phases 1-4 (1996-2011) were included. Median parathyroid hormone increased from phase 1 to phase 4 in all regions except for Japan, where it remained stable. Prescriptions of intravenous vitamin D analogs and cinacalcet increased and parathyroidectomy rates decreased in all regions over time. Compared with 150-300 pg/ml, in adjusted models, all-cause mortality risk was higher for parathyroid hormone=301-450 (hazard ratio, 1.09; 95% confidence interval, 1.01 to 1.18) and >600 pg/ml (hazard ratio, 1.23; 95% confidence interval, 1.12 to 1.34). Parathyroid hormone >600 pg/ml was also associated with higher risk of cardiovascular mortality as well as all-cause and cardiovascular hospitalizations. In a subgroup analysis of 5387 patients not receiving vitamin D analogs or cinacalcet and with no prior parathyroidectomy, very low parathyroid hormone (<50 pg/ml) was associated with mortality (hazard ratio, 1.25; 95% confidence interval, 1.04 to 1.51). In a large international sample of patients on hemodialysis, parathyroid hormone levels increased in most countries, and secondary hyperparathyroidism treatments changed over time. Very low and very high parathyroid hormone levels were associated with adverse outcomes. In the absence of definitive evidence in support of a specific parathyroid hormone target, there is an urgent need for additional research to inform clinical practice.


Comparison of amino acids physico-chemical properties and usage of late embryogenesis abundant proteins, hydrophilins and WHy domain.
Late Embryogenesis Abundant proteins (LEAPs) comprise several diverse protein families and are mostly involved in stress tolerance. Most of LEAPs are intrinsically disordered and thus poorly functionally characterized. LEAPs have been classified and a large number of their physico-chemical properties have been statistically analyzed. LEAPs were previously proposed to be a subset of a very wide family of proteins called hydrophilins, while a domain called WHy (Water stress and Hypersensitive response) was found in LEAP class 8 (according to our previous classification). Since little is known about hydrophilins and WHy domain, the cross-analysis of their amino acids physico-chemical properties and amino acids usage together with those of LEAPs helps to describe some of their structural features and to make hypothesis about their function. Physico-chemical properties of hydrophilins and WHy domain strongly suggest their role in dehydration tolerance, probably by interacting with water and small polar molecules. The computational analysis reveals that LEAP class 8 and hydrophilins are distinct protein families and that not all LEAPs are a protein subset of hydrophilins family as proposed earlier. Hydrophilins seem related to LEAP class 2 (also called dehydrins) and to Heat Shock Proteins 12 (HSP12). Hydrophilins are likely unstructured proteins while WHy domain is structured. LEAP class 2, hydrophilins and WHy domain are thus proposed to share a common physiological role by interacting with water or other polar/charged small molecules, hence contributing to dehydration tolerance.


Cyclic (alkyl)(amino)carbenes (CAACs): stable carbenes on the rise.
CONSPECTUS: Carbenes are compounds that feature a divalent carbon atom with only six electrons in its valence shell. In the singlet state, they possess a lone pair of electrons and a vacant orbital and therefore exhibit Lewis acidic and Lewis basic properties, which explains their very high reactivity. Following the preparation by our group in 1988 of the first representative, a variety of stable carbenes are now available, the most popular being the cyclic diaminocarbenes. In this Account, we discuss another class of stable cyclic carbenes, namely, cyclic (alkyl)(amino)carbenes (CAACs), in which one of the electronegative and π-donor amino substituents of diaminocarbenes is replaced by a σ-donating but not π-donating alkyl group. As a consequence, CAACs are more nucleophilic (σ-donating) but also more electrophilic (π-accepting) than diaminocarbenes. Additionally, the presence of a quaternary carbon in the position α to the carbene center provides steric environments that differentiate CAACs dramatically from all other ligands. We show that the peculiar electronic and steric properties of CAACs allow for the stabilization of unusual diamagnetic and paramagnetic main group element species. As examples, we describe the preparation of room temperature stable phosphorus derivatives in which the heteroatom is in the zero oxidation state, nucleophilic boron compounds, and phosphorus-, antimony-, boron-, silicon-, and even carbon-centered neutral and cationic radicals. CAACs are also excellent ligands for transition metal complexes. The most recent application is their use for the stabilization of paramagnetic complexes, in which the metal is often in a formal zero oxidation state. Indeed, bis(CAAC)M complexes in which the metal is gold, copper, cobalt, iron, nickel, manganese, and zinc have been isolated. Depending on the metal, the majority of spin density can reside either on the metal or on the carbene carbons and the nitrogen atoms of the CAAC ligand. In contrast to diaminocarbenes, the higher basicity of CAACs makes them poor leaving groups, and thus they cannot be used for classical organocatalysis. However, because of their superior electrophilicity and smaller singlet-triplet gap, CAACs can activate small molecules at room temperature, such as CO, H2, and P4, as well as enthalpically strong bonds, such as B-H, Si-H, N-H, and P-H. Lastly, excellent results have been obtained in palladium, ruthenium, and gold catalysis. CAAC-metal complexes are extremely thermally robust, which allows for their utilization in harsh conditions. This property has been used to perform a variety of gold-catalyzed reactions in the presence of basic amines, including ammonia and hydrazine, which usually deactivate catalysts.


Drip fertilization improve water and nitrogen use efficiency by optimizing root and shoot traits of winter wheat.
Proper irrigation and fertilization measures can not only improve water and fertilizer utilization efficiency, but also have important significance in ensuring agricultural environment security and sustainable development. A field experiment was conducted to determine the optimal drip fertilization measure of winter wheat and explain its mechanism by analyzing the physiological and ecological characteristics and utilization efficiency of water and nitrogen under different irrigation and fertilization methods. The plants were treated with three irrigation and fertilization methods: the traditional irrigation and fertilization method (CK), surface drip fertilization (I1) and underground drip fertilization (I2). The results demonstrated that different irrigation methods had various effects on population and physiological characteristics of wheat. The plant height, leaf area and tiller number of I1 were significantly higher than those of CK during the whole growth period. I2 decreased plant height, leaf area and tiller number at jointing stage, but at flowering stage, the leaf area of I2 t was significantly higher than that of CK. Different irrigation methods also affected the root distribution of wheat. At flowering stage, I1 had lower root biomass than CK in all soil layers. The upper root system of I2 was smaller, but the deep root system was larger compared with the control. I1 and I2 had lower total root weight and higher shoot biomass compared to CK, so their root-shoot ratio decreased significantly. I1 and I2 increased and instantaneous water use efficiency (IWUE) by increasing the photosynthetic rate (Pn) and reducing transpiration rate (Tr) at the flowering stage, while I2 had a similar Pn to I1, but reduced Tr, resulting in a higher IWUE than I1. Both I1 and I2 also increased root efficiency, root activity, and Fv/Fm of wheat at the late growth stage, promoting accumulated dry matter after flowering (ADM) and pre-flowering dry matter remobilization (DMR), leading to a significant increase in grain yield. In addition, I1 and I2 had significantly higher water productivity (WP), irrigation water productivity (IWP), nitrogen partial productivity (NPP) and nitrogen agronomic efficiency (NAE) than CK, especially I2 had the highest IWP, WP, NPP and NAE. These findings highlight the potential benefits of drip fertilization in promoting sustainable wheat production and elucidate the mechanism by which it promotes efficient use of water and fertilizer.


[Riva-Rocci and blood pressure].
Scipione Riva-Rocci (1863-1937) was educated in Turin as a physician and later as a doctor of internal medicine. In 1896 and 1897 he published a series of four articles (in Italian) on a new method for measuring blood pressure. Previous non-invasive methods were all based on compression of the radial pulse, in keeping with centuries of medical tradition, but they were cumbersome and unreliable. Riva-Rocci's innovation consisted in compressing the brachial artery instead, at the level of the upper arm. For this purpose he devised an inflatable rubber tube, which was rigid on the outside. Disappearance of the radial pulse on palpation indicated the systolic arterial pressure, as Riva-Rocci confirmed by calibration experiments in animals and with human cadavers. His instrument was introduced world-wide after a chance visit by the American neurosurgeon Harvey Cushing (1869-1939). The Russian surgeon Nikolai Korotkoff (1874-1920) was the first to apply auscultation of the artery below the cuff (in 1905), a method that allowed determination of diastolic arterial pressure. Riva-Rocci was Chief of Medicine at the municipal hospital in Varese from 1900 to 1928, where he developed a special interest in paediatrics.


Persistent fibrosis, hypertrophy and sarcomere disorganisation after endoscopy-guided heart resection in adult Xenopus.
Models of cardiac repair are needed to understand mechanisms underlying failure to regenerate in human cardiac tissue. Such studies are currently dominated by the use of zebrafish and mice. Remarkably, it is between these two evolutionary separated species that the adult cardiac regenerative capacity is thought to be lost, but causes of this difference remain largely unknown. Amphibians, evolutionary positioned between these two models, are of particular interest to help fill this lack of knowledge. We thus developed an endoscopy-based resection method to explore the consequences of cardiac injury in adult Xenopus laevis. This method allowed in situ live heart observation, standardised tissue amputation size and reproducibility. During the first week following amputation, gene expression of cell proliferation markers remained unchanged, whereas those relating to sarcomere organisation decreased and markers of inflammation, fibrosis and hypertrophy increased. One-month post-amputation, fibrosis and hypertrophy were evident at the injury site, persisting through 11 months. Moreover, cardiomyocyte sarcomere organisation deteriorated early following amputation, and was not completely recovered as far as 11 months later. We conclude that the adult Xenopus heart is unable to regenerate, displaying cellular and molecular marks of scarring. Our work suggests that, contrary to urodeles and teleosts, with the exception of medaka, adult anurans share a cardiac injury outcome similar to adult mammals. This observation is at odds with current hypotheses that link loss of cardiac regenerative capacity with acquisition of homeothermy.


Identifying and Classifying Pollution Hotspots to Guide Watershed Management in a Large Multiuse Watershed.
In many locations around the globe, large reservoir sustainability is threatened by land use change and direct pollution loading from the upstream watershed. However, the size and complexity of upstream basins makes the planning and implementation of watershed-scale pollution management a challenge. In this study, we established an evaluation system based on 17 factors, representing the potential point and non-point source pollutants and the environmental carrying capacity which are likely to affect the water quality in the Dahuofang Reservoir and watershed in northeastern China. We used entropy methods to rank 118 subwatersheds by their potential pollution threat and clustered subwatersheds according to the potential pollution type. Combining ranking and clustering analyses allowed us to suggest specific areas for prioritized watershed management (in particular, two subwatersheds with the greatest pollution potential) and to recommend the conservation of current practices in other less vulnerable locations (91 small watersheds with low pollution potential). Finally, we identified the factors most likely to influence the water quality of each of the 118 subwatersheds and suggested adaptive control measures for each location. These results provide a scientific basis for improving the watershed management and sustainability of the Dahuofang reservoir and a framework for identifying threats and prioritizing the management of watersheds of large reservoirs around the world.


Visualizing Nanoscale Coronal Segregation in Rod-Like Micelles Formed by Co-Assembly of Binary Block Copolymer Blends.
Mixed micelles formed by co-assembly of pairs of block copolymers (BCPs) can develop novel morphologies and generate useful properties not accessible from homomicelles. For micelles consisting of two different polymers in the corona, identifying the location of the corona chains is a critical part of morphology characterization. Coronal segregation in mixed micelle is often characterized by transmission electron microscopy in combination with selective staining of individual polymers. In this study, Karstedt's catalyst is used for selective Pt(0)-olefin coordination staining of polyisoprene (PI) and poly(methylvinylsiloxane) (PMVS) corona chains in the presence of poly(dimethylsiloxane) (PDMS) corona chains in cylindrical mixed micelles with a crystalline poly(ferrocenyldimethylsilane) (PFS) core. Previous experiments using OsO4 as a stain did not enable visualization of nanoscale coronal segregation in mixed micelles obtained from co-assembly of PFS-b-PI and PFS-b-PDMS, as well as PFS-b-PMVS and PFS-b-PDMS.


DNA sequence recognition by bispyrazinonaphthalimides antitumor agents.
Bifunctional DNA intercalating agents have long attracted considerable attention as anticancer agents. One of the lead compounds in this category is the dimeric antitumor drug elinafide, composed of two tricyclic naphthalimide chromophores separated by an aminoalkyl linker chain optimally designed to permit bisintercalation of the drug into DNA. In an effort to optimize the DNA recognition capacity, different series of elinafide analogues have been prepared by extending the surface of the planar drug chromophore which is important for DNA sequence recognition. We report here a detailed investigation of the DNA sequence preference of three tetracyclic monomeric or dimeric pyrazinonaphthalimide derivatives. Melting temperature measurements and surface plasmon resonance (SPR) studies indicate that the dimerization of the tetracyclic planar chromophore considerably augments the affinity of the drug for DNA, polynucleotides, or hairpin oligonucleotides and promotes selective interaction with G.C sites. The (CH(2))(2)NH(CH(2))(3)NH(CH(2))(2) connector stabilizes the drug-DNA complexes. The methylation of the two nitrogen atoms of this linker chain reduces the binding affinity and increases the dissociation rates of the drug-DNA complexes by a factor of 10. DNase I footprinting experiments were used to investigate the sequence selectivity of the drugs, demonstrating highly preferential binding to G.C-rich sequences. It also served to select a high-affinity site encompassing the sequence 5'-GACGGCCAG which was then introduced into a biotin-labeled hairpin oligonucleotide to accurately measure the binding parameters by SPR. The affinity constant of the unmethylated dimer for this sequence is 500 times higher than that of the monomer compound and approximately 10 times higher than that of the methylated dimer. The DNA groove accessibility was also probed with three related oligonucleotides carrying G --> c(7)G, G --> I, and C --> M substitutions. The level of drug binding to the two hairpin oligonucleotides containing 7-deazaguanine (c(7)G) or 5-methylcytosine (M) residues is unchanged or only slightly reduced compared to that of the unmodified target. In contrast, incorporation of inosine (I) residues considerably decreases the extent of drug binding or even abolishes the interaction as is the case with the monomer. The pyrazinonaphthalimide derivatives are thus much more sensitive to the deletion of the exocyclic guanine 2-amino group exposed in the minor groove of the duplex than to the modification of the major groove elements. The complementary SPR footprinting methodology combining site selection and quantitative DNA affinity analysis constitutes a reliable method for dissecting the DNA sequence selectivity profile of reversible DNA binding small molecules.


Inscription and characterization of waveguides written into borosilicate glass by a high-repetition-rate femtosecond laser at 800 nm.
A series of waveguides was inscribed in a borosilicate glass (BK7) by an 11 MHz repetition rate femtosecond laser operating with pulse energies from 16 to 30 nJ and focused at various depths within the bulk material. The index modification was measured using a quantitative phase microscopy technique that revealed central index changes ranging from 5 x 10(-3) to 10(-2), leading to waveguides that exhibited propagation losses of 0.2 dB/cm at a wavelength of 633 nm and 0.6 dB/cm at a wavelength of 1550 nm with efficient mode matching, less than 0.2 dB, to standard optical fibers. Analysis of the experimental data shows that, for a given inscription energy, the index modification has a strong dependence on inscription scanning velocity. At higher energies, the index modification increases with increasing inscription scanning velocity with other fabrication parameters constant.


Femtosecond laser ablation by bibursts in the MHz and GHz pulse repetition rates.
Here, to the best of our knowledge, for the first time we report an in-depth experimental study of high ultrafast laser ablation efficiency for processing of copper and steel with single-pulses, MHz, GHz, and burst-in-the-burst (biburst) regimes. The comparison of burst, biburst, and single-pulse ablation efficiencies was performed for beam-size-optimised regimes, showing the real advantages and disadvantages of milling and drilling processing approaches. Highly efficient ultrashort pulse laser processing was achieved for ∼1 µm optical wavelength: 8.8 µm3/µJ for copper drilling, 5.6 µm3/µJ for copper milling, and 6.9 µm3/µJ for steel milling. We believe that the huge experimental data collected in this study will serve well for the better understanding of laser burst-matter interaction and theoretical modelling.


MAPK pathways are involved in the inhibitory effect of berberine hydrochloride on gastric cancer MGC 803 cell proliferation and IL-8 secretion in vitro and in vivo.
Gastric cancer is the second leading cause of cancer-associated mortality worldwide. This investigation aimed to identify whether the mitogen‑activated protein kinase (MAPK) signaling pathways are involved in the inhibitory effect of berberine hydrochloride (BER) on MGC 803 cells in vitro and in vivo. BER time‑ and dose‑dependently inhibited proliferation of MGC 803 cells. It also suppressed tumorigenesis in nude mice xenografted with MGC 803 cells. Additionally, BER reduced interleukin‑8 (IL‑8) secretion in vitro and in vivo. Further investigation demonstrated that inactivation of p38 MAPK, extracellular-signal regulated kinase 1/2 and c‑Jun N‑terminal kinase by BER contributed to the decreased proliferation and tumorigenesis, and the change in IL‑8 expression levels. However, there was no significant synergistic inhibitory effect of combined BER and evodiamine (EVO) treatment on tumorigenesis, and BER reduced the upregulation of IL‑8 induced by EVO in vivo. The results of the current study suggested that BER may be an effective and safe drug candidate for treating gastric cancer via modulation of the MAPK signaling pathways.


Evidence of oxidative stress in the renal cortex of diabetic rats: favourable effect of vitamin E.
The aim of this study was to determine whether there are any disturbances of red/ox balance in the renal cortex of rats during the course of experimental diabetes. In the renal cortex of rats with streptozotocin-induced diabetes, the activity of superoxide dismutase (SOD) isoenzymes, glutathione peroxidase (GSH-Pox). glutathione S-transferase (GST) and glutathione reductase (GSH-RED) was measured in the 5th, 10th and 15th weeks of diabetes. Free radical cell damage was assessed on the basis of malonyldialdehyde (MDA) concentration. The influence of lipophilic antioxidant vitamin E on these analytes was also studied. An increase in MDA concentration in the 10th and 15th weeks of diabetes correlated significantly with plasma glucose concentration (r=0.47; p<0.001). Moreover, MDA concentration was influenced by time (+); p<0.001, diabetes (+); p<0.001, vitamin E (-) p<0.001 (ANOVA). Plasma creatinine concentration in rats was elevated by diabetes (p<0.001), whereas vitamin E decreased the concentration (p<0.05). Vitamin E lowered the activity of GSHPox (p<0.001) and GST (p<0.01) (ANOVA). Our results indicate that during experimental diabetes, disturbances of red/ox balance lead to disturbance in renal function manifested as increased creatinine blood concentration. We suggest that oral supplementation of vitamin E protects the renal cortex of rats during experimental diabetes.


The Resistance of Cancer Cells to Palbociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor, is Mediated by the ABCB1 Transporter.
Palbociclib was approved by the United States Food and Drug Administration for use, in combination with letrozole, as a first-line treatment for estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) postmenopausal metastatic breast cancer. However, recent studies show that palbociclib may be an inhibitor of the ABCB1 transporter, although this remains to be elucidated. Therefore, we conducted experiments to determine the interaction of palbociclib with the ABCB1 transporter. Our in vitro results indicated that the efficacy of palbociclib was significantly decreased in the ABCB1-overexpressing cell lines. Furthermore, the resistance of ABCB1-overexpressing cells to palbociclib was reversed by 3 μM of the ABCB1 inhibitor, verapamil. Moreover, the incubation of ABCB1-overexpressing KB-C2 and SW620/Ad300 cells with up to 5 μM of palbociclib for 72 h, significantly upregulated the protein expression of ABCB1. The incubation with 3 µM of palbociclib for 2h significantly increased the intracellular accumulation of [3H]-paclitaxel, a substrate of ABCB1, in ABCB1 overexpressing KB-C2 cells but not in the corresponding non-resistant parental KB-3-1 cell line. However, the incubation of KB-C2 cells with 3 μM of palbociclib for 72 h decreased the intracellular accumulation of [3H]-paclitaxel due to an increase in the expression of the ABCB1 protein. Palbociclib produced a concentration-dependent increase in the basal ATPase activity of the ABCB1 transporter (EC50 = 4.73 μM). Molecular docking data indicated that palbociclib had a high binding affinity for the ABCB1 transporter at the substrate binding site, suggesting that palbociclib may compete with other ABCB1 substrates for the substrate binding site of the ABCB1. Overall, our results indicate that palbociclib is a substrate for the ABCB1 transporter and that its in vitro anticancer efficacy is significantly decreased in cancer cells overexpressing the ABCB1.


Ebselen enhances insulin sensitivity and decreases oxidative stress by inhibiting SHIP2 and protects from inflammation in diabetic mice.
Ebselen, a multifunctional organoselenium compound, has been recognized as a potential treatment for diabetes-related disorders. However, the underlying mechanisms whereby ebselen regulates metabolic pathways remain elusive. We discovered that ebselen inhibits lipid phosphatase SHIP2 (Src homology 2 domain-containing inositol-5-phosphatase 2), an emerging drug target to ameliorate insulin resistance in diabetes. We found that ebselen directly binds to and inhibits the catalytic activity of the recombinant SHIP2 phosphatase domain and SHIP2 in cultured cells, the skeletal muscle and liver of the diabetic db/db mice, and the liver of the SHIP2 overexpressing (SHIP2-Tg) mice. Ebselen increased insulin-induced Akt phosphorylation in cultured myotubes, enhanced insulin sensitivity and protected liver tissue from lipid peroxidation and inflammation in the db/db mice, and improved glucose tolerance more efficiently than metformin in the SHIP2-Tg mice. SHIP2 overexpression abrogated the ability of ebselen to induce glucose uptake and reduce ROS production in myotubes and blunted the effect of ebselen to inhibit SHIP2 in the skeletal muscle of the SHIP2-Tg mice. Our data reveal ebselen as a potent SHIP2 inhibitor and demonstrate that the ability of ebselen to ameliorate insulin resistance and act as an antioxidant is at least in part mediated by the reduction of SHIP2 activity.


Regulatable Transgene Expression for Prevention of Chemotherapy-Induced Peripheral Neuropathy.
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating complication associated with drug treatment of cancer for which there are no effective strategies of prevention or treatment. In this study, we examined the effect of intermittent expression of neurotophin-3 (NT-3) or interleukin-10 (IL-10) from replication-defective herpes simplex virus (HSV)-based regulatable vectors delivered by subcutaneous inoculation to the dorsal root ganglion (DRG) on the development of paclitaxel-induced peripheral neuropathy. We constructed two different tetracycline (tet)-on-based regulatable HSV vectors, one expressing NT-3 and the other expressing IL-10, in which the transactivator expression in the tet-on system was under the control of HSV latency-associated promoter 2 (LAP-2), and expression of the transgene was controlled by doxycycline (DOX). We examined the therapeutic effect of intermittent expression of the transgene in animals with paclitaxel-induced peripheral neuropathy modeled by intraperitoneal injection of paclitaxel (16 mg/kg) once a week for 5 weeks. Intermittent expression of either NT-3 or IL-10 3 days before and 1 day after paclitaxel administration protected animals against paclitaxel-induced peripheral neuropathy over the course of 5 weeks. These results suggest the potential of regulatable vectors for prevention of chemotherapy-induced peripheral neuropathy.


Immunohistochemical study of the catecholaminergic systems in the lower brain stem of the human infant.
The study of catecholaminergic (CA) systems in the lower brain stem was undertaken in the infant. A method of indirect immunohistofluorescence using antibodies to tyrosine-hydroxylase (TH) was applied to five brains from infants whose deaths had no neurological cause; two brains were submitted to fully systematic investigation. A topographical and morphocytological analysis of the CA systems was carried out on horizontal serial sections. A neuronal map is shown presenting four bulbar and four pontine sections. The disposition of the main CA groups (i.e. A1, A2, locus coeruleus) was found to be consistent with the data provided by the literature concerning the human foetus and the adult. Topographic differences and peculiarities are emphasized in the infant. Mapping of phenylethanolamine N methyltransferase (PNMT) positive neurons was performed in one plane of section of mid-medulla. This technique might usefully be applied to the exploration of putative diseases of bulbopontine CA systems, such as the sudden infant death syndrome and central blood pressure disorders.


Spiral phase velocity mapping of left and right coronary artery blood flow: correction for through-plane motion using selective fat-only excitation.
To develop a method of correcting both right and left coronary artery flow velocities for the through-plane motion of the vessel, in order to allow details in the temporal flow profiles to be viewed. The methods developed use selective excitation and velocity mapping of the epicardial fat surrounding the artery, either in a separate acquisition (temporal resolution = 22 msec) or interleaved with the water-excitation acquisition (temporal resolution = 44 msec) used to determine coronary blood flow velocities. The two methods were compared in 10 right and 13 left coronary arteries in healthy volunteers. For the right coronary arteries, correction for through-plane motion significantly reduces the mean systolic flow velocity (75.3 mm/second vs. 90.0 mm/second, P < 0.01), while the mean diastolic flow velocity is unchanged (96.8 mm/second vs. 94.5 mm/second, P = ns). The resulting profiles are biphasic, with approximately equal flow in systole and diastole. For the left arteries, correction for through-plane motion reduces the mean systolic flow velocity (25.0 mm/second vs. 72.8 mm/second, P < 0.001), resulting in the expected diastolic predominant flow profiles. For the right arteries, there were no significant differences in the mean systolic and mean diastolic velocities after correction with the separate fat-excitation acquisition, and after correction the poorer temporal resolution combined water excitation/fat excitation acquisition. However, for the left coronary arteries, the combined water excitation/fat excitation acquisition resulted in a slight reduction in the mean diastolic velocity (121.5 mm/second vs. 130.9 mm/second, P < 0.05). Selective excitation of the surrounding epicardial fat enables through-plane correction of both left and right coronary flow velocities, enabling the temporal details of flow velocity to be viewed. With a combined WE/FE acquisition, this can be performed without extending the study duration; however, the reduced temporal resolution and temporal mismatch of the excitations results in a blunting of rapidly changing flow profiles. As such, it may be less suitable for the left coronary artery, which has a greater range of through-plane motion than the right, and correction using separate WE and FE acquisitions, or the adjacent myocardium, may be preferable.


[Cancer risk of the stomach resected for ulcer. The role of duodenogastric reflux (author's transl)].
The purpose of this study was to find whether the reflux of bile and pancreatic juices following stomach resection (duodenogastric reflux) enhances the incidence of carcinomas near the gastroenteric anastomosis. 72 male Wistar rats were subjected to stomach resection. The gastroenteric anastomosis (GE) was performed either as short loop anastomosis (Billroth II; n = 39), thus providing a continuous duodenogastric reflux, or as Y-shaped GE (according to Roux; n = 33). By the latter technique, bile and pancreatic juices are derived quantitatively into the jejunum without coming into contact with the remaining part of the stomach. During a period of 33 weeks, operated rats as well as intact animals were given the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (NG; 120 mg/l) in the drinking water. At autopsy, 33 to 36 weeks after daily oral administration of NG, most of the tumours were found in operated rats undergoing continuous reflux (Billroth II group). In contrast to these findings, the incidence or carcinomas was significantly lower in animals without reflex (Roux group or intact control rats).-The results of our experiments demonstrate that, in rats, the duodenogastric reflux contributes substantially to the development of carcinomas of the resected stomach.


Full-length sequencing and genomic characterization of Bagaza, Kedougou, and Zika viruses.
Many members of the genus Flavivirus are the agents of important diseases of humans, livestock, and wildlife. Currently, no complete genome sequence is available for the three African viruses, Bagaza, Zika, and Kedougou viruses, each representing a distinct virus subgroup according to the latest virus classification. In this study, we obtained a complete genome sequence of each of those three viruses and characterized the open reading frames (ORFs) with respect to gene sizes, cleavage sites, potential glycosylation sites, distribution of cysteine residues, and unique motifs. The sequences of the three viruses were then scanned across the entire length of the ORF against available sequences of other African flaviviruses and selected reference viruses for genetic relatedness. The data collectively indicated that Kedougou virus was close to dengue viruses but nonetheless distinct, while Bagaza virus shared genetic relatedness with West Nile virus in several genomic regions. In the non-coding regions, it was found that a particular organizational pattern of conserved sequences in the 3' terminal region generally correlated with the current virus grouping.


Inactivation of the flax rust resistance gene M associated with loss of a repeated unit within the leucine-rich repeat coding region.
The M rust resistance gene from flax was cloned after two separate approaches, an analysis of spontaneous M mutants with an L6 gene-derived DNA probe and tagging with the maize transposon Activator, independently identified the same gene. The gene encodes a protein of the nucleotide binding site leucine-rich repeat class and is related (86% nucleotide identity) to the unlinked L6 rust resistance gene. In contrast to the L locus, which contains a single gene with multiple alleles, approximately 15 related genes occur at the complex M locus, with only one encoding the M resistance specificity. The M protein contains two direct repeats of 147 and 149 amino acids in the C-terminal part of the leucine-rich region. Three mutant alleles of M encoding a product containing a single repeat unit of 154 amino acids were isolated. The mutant DNA sequences probably occurred by unequal intragenic exchange in the coding region of the repeats. The recombinant alleles lost M resistance and gained no detectable new resistance specificity.


Protective effects of Vitamin C against spinal cord injury-induced renal damage through suppression of NF-κB and proinflammatory cytokines.
Spinal cord injury [SCI] leads to complex cellular and molecular interactions which affects various organ systems. The present study focused on determining the protection offered by Vitamin C against spinal injury-induced kidney damage in wistar rats. The experimental protocol was performed with three groups; Sham, SCI and Vitamin C [20 mg/kg/bw] followed by SCI. The kidney tissue was investigated for oxidative stress parameters [reactive oxygen species, protein carbonyl, sulphydryl content, thiobarbituric acid reactive species [TBARS], and myeloperoxidase activity] and antioxidant status [glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase activity]. Further, inflammation studies were performed by analyzing expression of NF-κB, cycloxygenase-2, iNOS through western blot analysis and inflammatory cytokines by TNF-α and IL-1β levels. The present study shows clear evidence that Vitamin C treatment abrogated spinal injury-induced oxidative stress and inflammatory responses and enhanced the antioxidant status. Thus, the protection offered by Vitamin C against spinal cord injury-induced kidney damage is attributed to its anti-oxidant and anti-inflammatory effects.


[Colorectal stents: efficacy and complications in our center].
in emergency surgery, colorectal mortality is very high compared with elective surgery. An alternative is placement of endoscopic stents to correct the bowel obstruction and then allow elective surgery. Moreover, it is possible to use stents in the palliative treatment of patients at high surgical risk or with unresecable tumors. The aim of this study is to evaluate the rates of technical and clinical success and complications of colorectal stent placement over the past 5 years. retrospective study of 33 patients in which stents were placed since 2006 to 2011. Variables were analyzed: 1) the indication (palliation or "bridge to surgery"), 2) rates of technical success and clinical success, and 3) complications (perforation, migration, bleeding, and reocclusion). in 24 patients the prosthesis was placed as a palliative treatment (72.7%) and in 9 cases as a "bridge to surgery". The technical success rate was 87.87% and 82.14% clinical success. There were five cases of bowel perforation with high pneumoperitoneum and a case of microperforation (18.1%). Five patients had reocclusion (17.2%); there were 3 and 4 with bleeding and migration. Three patients died within 24 hours after endoscopic treatment. In 9 cases of "bridge to surgery," technical success was 100% and 77% clinical success. One patient required emergency surgery due to migration of the prosthesis and reocclusion and another colonic perforation. endoscopic treatment is a good option as a transitional step to elective surgery or palliative treatment. But serious complications such as perforation or reocclusion should be considered.


Resident selection: are we putting the cart before the horse?
The selection of orthopaedic residents is a formidable task. We must put the horse, namely, the consideration of certain societal goals and responsibilities, before the cart, namely, the selection criteria and processes themselves. The recommendation is that the outcomes of our training programs produce, in addition to excellent clinical orthopaedists, some graduates with competence and talent in contribution to diversity, culturally competent care, assistance with elimination of healthcare disparities, skills in research, talent in leadership, skills in administration, and abilities in education. Once specific outcome goals are identified, efforts can be directed to learning to recognize and evaluate the potentials and success foreshadowing characteristics of applicants that predict, or are associated with, the desired outcome competencies. Traditional screening and selection of applicants based largely on grades, test scores, and election to Alpha Omega Alpha honorary society have certain historically based biases and limitations. The historic ethnocentric impacts on Western medical culture are profound, long-standing, and thoroughly interwoven into the fabric of our profession. It is necessary to substantially change our residency selection if we are to achieve some highly significant humanitarian and pragmatic societal goals.