bluuebunny/crossref_metadata_2025 huggingface dataset:
Anthropometric measurements as predictors of cephalopelvic disproportion
Authors: BENJAMIN SANTOSH J , DANIEL ANJALI B , KAMATH ASHA , RAMKUMAR VANI
Published: September 2011

Objective. We assessed the efficacy of maternal anthropometric measurements and clinical estimates of fetal weight in isolation and in combination as predictors of cephalopelvic disproportion (CPD). Design. Prospective cohort study. Setting. Tertiary care teaching hospital, two affiliated hospitals with facilities for conducting cesarean delivery and seven affiliated primary care facilities with no operation theaters. Sample. Primigravidae over 37 weeks’ gestation attending these facilities during a 20‐month period with a singleton pregnancy in vertex presentation. Methods. Several anthropometric measurements were taken in 249 primigravidae. Fetal weight was estimated. Differences in these measurements between the vaginal delivery and CPD groups were analyzed. The validity of these measurements in predicting CPD was analyzed by plotting receiver operating characteristic curves and by logistic regression analysis. Main outcome measure. Mode of delivery. Results. Maternal height, foot size, inter‐trochanteric diameter and bis‐acromial diameter showed the highest positive predictive values for CPD. Combining some maternal measurements with estimates of fetal weight increased predictive values modestly, which are likely to be greater if the estimates of fetal weight are close to the actual birth weight. Based on multivariate analysis the risk factors for CPD in our population were foot length ≤23cm, inter‐trochanteric diameter ≤30cm and estimated fetal weight ≥3 000g. Conclusions. Maternal anthropometric measurements can predict CPD to some extent. Combining maternal measurements with clinical estimates of fetal weight only enhances the predictive value to a relatively modest degree (positive predictive value 24%).
Platelet antibodies and fetal growth: maternal antibodies against fetal platelet antigen 1a are strongly associated with reduced birthweight in boys
Authors: TILLER HEIDI , KILLIE METTE KJÆR , HUSEBEKK ANNE , SKOGEN BJØRN , NI HEYU , KJELDSEN‐KRAGH JENS , ØIAN PÅL
Published: September 2011

Objective. To assess whether maternal HPA 1a alloimmunization is associated with birthweight. Design. A retrospective observational cohort study. Setting. The national reference laboratory for clinical platelet immunology at a university hospital. Population. 165 HPA 1a incompatible pregnancies identified from a recent screening study of 100 448 women (124 pregnancies) and the national reference laboratory for clinical platelet immunology (41 pregnancies). Methods. A linear mixed model analysis was used to assess whether maternal anti‐HPA 1a antibodies were associated with birthweight. A generalized linear model was used to assess maternal anti‐HPA 1a antibodies as risk factor for small‐for‐gestational age neonates. Both models were adjusted for gestational age at time of delivery, maternal age, parity, smoking habits during pregnancy, preeclampsia, diabetes mellitus and fetal sex. Main outcome measures. Maternal anti‐HPA 1a antibody as risk factor of reduced birthweight and small‐for‐gestational age neonates. Results. The level of maternal anti‐HPA 1a antibodies was significantly associated with birthweight and risk of small‐for‐gestational age neonates after correcting for confounding variables (p<0.001). However, this association was only significant for boys. When the mother had high levels of anti‐HPA 1a antibodies during pregnancy, the adjusted mean birthweight in boys was 530g lower compared with anti‐HPA 1a antibody negative pregnancies (p<0.001). Conclusions. A linear relation between maternal anti‐HPA 1a antibody levels and reduced birthweight in boys was demonstrated. Reduced birthweight should be considered a possible complication of fetal and neonatal alloimmune thrombocytopenia.
Long‐term outcome of porcine skin graft in surgical treatment of recurrent pelvic organ prolapse. An open randomized controlled multicenter study
Authors: DAHLGREN EVA , KJØLHEDE PREBEN ,   on behalf of the RPOP‐PELVICOL Study Group
Published: September 2011

Objective. To determine the long‐term objective and subjective outcomes of use of a porcine skin graft (Pelvicol™) compared with conventional colporrhaphy in recurrent pelvic organ prolapse surgery and to analyze risk factors and safety. Design. Open randomized controlled multicenter study. Setting. Eight Swedish hospitals. Population. 135 consecutive women with recurrent cystocele and/or rectocele admitted for vaginal prolapse surgery; 132 completed the study, 64 were randomly allocated to receive conventional colporrhaphy and 68 to Pelvicol. Methods. Conventional anterior and posterior colporrhaphy and colporrhaphy with use of Pelvicol™ mesh reinforcement. Clinical evaluation by means of pelvic organ prolapse quantification (POP‐Q) and symptom questionnaire preoperatively, three months and three years postoperatively. Main outcome measures. Anatomical and subjective outcome.  Recurrence was defined as POP‐Q≥stage 2. Results. At three‐month follow‐up, early recurrence/surgical failures occurred significantly more often in the Pelvicol™ group, but at the three‐year follow‐up the recurrence rates were similar. The recurrence rates in the anterior compartment were 57–62% and 44–23% in the posterior compartment for the colporrhaphy and Pelvicol™ groups, respectively. Symptoms were substantially and equally reduced in the two groups after surgery. Sexual activity and function did not seem to be affected adversely in any group. The complication rate was low. Risk factors for anatomical recurrence were age, body mass index and preoperative stage of the prolapse. Conclusions. With the surgical technique used in this study, Pelvicol™ did not provide advantages over conventional colporrhaphy in recurrent pelvic organ prolapse concerning anatomical and subjective outcomes.
First trimester prediction of small‐ and large‐for‐gestation neonates by an integrated model incorporating ultrasound parameters, biochemical indices and maternal characteristics
Authors: PAPASTEFANOU IOANNIS , SOUKA ATHENA P. , PILALIS ATHANASIOS , ELEFTHERIADES MAKARIOS , MICHALITSI VASILIKI , KASSANOS DEMETRIOS
Published: September 2011

Objective. To identify maternal/pregnancy characteristics, first trimester ultrasound parameters and biochemical indices which are significant independent predictors of small‐for‐gestational age (SGA) and large‐for‐gestational age (LGA) neonates. Design. Retrospective cross‐sectional study. Setting. Two fetal Medicine Units. Population. 4 702 singleton pregnancies presenting for screening for chromosomal abnormalities by nuchal translucency and maternal serum biochemistry at 11–14 weeks. Methods. Reference ranges for birthweight applied to our population were constructed by the Royston and Wright method. Multiple logistic regression was applied to develop first trimester prediction models for SGA and LGA. Main outcome measures. Birth of SGA or LGA neonate. Results. Maternal height, parity, smoking, assisted conception, delta crown–rump length, delta nuchal translucency, free beta human chorionic gonadotrophin and pregnancy‐associated plasma protein‐A were significant independent predictors of SGA. Maternal weight and height, smoking, delta crown–rump length and delta nuchal translucency were significant independent predictors of LGA. Models for SGA (AUC=0.7296, CI: 0.69–0.76, p<0.0001) and LGA (AUC=0.6901, CI: 0.65–0.72, p<0.0001) were derived, applicable to routine obstetric population at low risk for these conditions. For 20% screen positive rate the modeling achieves sensitivities of about 55% for SGA and 48% for LGA neonates. Conclusion. Prediction for birthweight deviations is feasible using data available at the routine 11–14 weeks’ examination. Delta CRL and delta nuchal translucency were significant independent predictors for both SGA and LGA.
The potential effects of cholecalciferol on bone regeneration in dogs
Authors: Hong Hsiang‐Hsi , Chou Ting‐An , Yang Jen‐Chang , Chang Chee‐Jen
Published: September 2011

Objectives

The aim of this investigation was to evaluate the potential effects of the systemically delivered combination of calcium supplementation and cholecalciferol and of the locally applied biphasic calcium alloplast on the surgically produced alveolar sockets at the early healing stage in a dog model.

Materials and methods

The mandibular pre‐molars of nine Beagle dogs were extracted first. Three months later, four standardized sockets with a 4 mm in diameter and 6 mm deep cylinder were created bilaterally at healed extraction sites. The sockets on one side were grafted with biphasic calcium phosphate alloplast, whereas the defects on the other side were left un‐grafted. The dogs were then randomly divided into two groups; five dogs received oral calcium and cholecalciferol combination (Vit.D/Ca) and were assigned to the test group (Vit.D/Ca Group). The other four dogs without Vit.D/Ca supplement were distributed to the control group (Non‐Vit.D/Ca Group). The bone density (Density) and the implant stability quotient (ISQ) at prepared sites were measured 4 weeks later. The drawn bone cores were examined by a histomorphometric analysis for measurement of new bone formation (NBF). The amount of vertical ridge resorption (VRR) was evaluated.

Results

The Vit.D/Ca‐treated subjects revealed significantly more NBF (P < 0.05), higher bone density (P < 0.05) and significantly less vertical ridge reduction (P < 0.05) in the healing sockets than those without Vit.D/Ca treatment. The non‐grafted sockets demonstrated significantly more NBF (P < 0.05), higher bone density (P < 0.05), better ISQ value (P < 0.05) and more vertical ridge reduction (P < 0.05) than those in the grafted sockets. There was no significant difference between the serum data determined before and 4 weeks after experiment in Vit.D/Ca Group or Non‐Vit.D/Ca Group. However, the changed value (post‐op vs. pre‐op) between the two groups was significant in the serum level of phosphate and parathyroid hormone (P = 0.05).

Conclusion

The results of the present study indicated that the examined calcium phosphate alloplast may perform a function in alveolar ridge preservation while reducing the potential of NBF potential in the healing extraction socket. Also, the combination of calcium supplementation and cholecalciferol may have systemic effects on accelerating bone regeneration.
Retracted: Peri‐implant bone reactions to immediate implants placed at different levels in relation to crestal bone. Part II: a pilot study in dogs
Authors: Negri Bruno , Calvo‐Guirado José Luis , Ramírez‐Fernández María Piedad , Maté Sánchez‐de Val José , Guardia Javier , Muñoz‐Guzón Fernando
Published: September 2011

Purpose:

The aim of the present study was to evaluate bone‐to‐implant contact (BIC) and bone remodeling dynamics after immediate implant placement at different levels in relation to the crestal bone with two different implant designs in beagle dogs.

Materials and methods:

The mandibular second, third and fourth premolars of six beagle dogs were extracted bilaterally and three implants were immediately placed in the hemi‐arches of each dog. Randomly, three cylindrical and three tapered implants were inserted crestally (control group) or 2 mm subcrestally (test group). Both groups were treated with a minimal mucoperiosteal flap elevation approach. A gap from the buccal cortical wall to the implant was always left. Three dogs were allowed a 4‐week submerged healing period and the other three an 8‐week submerged healing period. The animals were sacrificed and samples were obtained. Biopsies were processed for ground sectioning. Histomorphometric analysis was carried out in order to compare BIC, de novo bone formation and bone remodeling.

Results:

All implants osseointegrated clinically and histologically. Healing patterns examined microscopically at 4 and 8 weeks for both groups (crestal and subcrestal) yielded similar qualitative bone findings. The total BIC mean value for the crestal group was 36.48 ± 3.4% and for the subcrestal group was 41.46 ± 4.2%. The mean percentage of newly formed BIC was greater with the cylindrical implant design (46.06 ± 1.09%) than with the tapered design (33.89 ± 1.72%). There was less bone resorption in the subcrestal group (test) than crestal group (control).

Conclusion:

These findings suggest that apical positioning of the top of the implant does not jeopardize bone crest and peri‐implant tissue remodeling. However, less resorption of the lingual crest may be expected when implants are placed 2 mm subcrestally. Moreover, higher BIC values were found in cylindrical implants placed subcrestally.
Immediate rehabilitation of the edentulous mandible with screw type implants: results after up to 10 years of clinical function
Authors: Heschl Alexander , Payer Michael , Platzer Susanne , Wegscheider Walther , Pertl Christof , Lorenzoni Martin
Published: September 2011

Objectives

The aim of this prospective case series was to evaluate the results of an immediate loading concept using four Xi VE S plus implants in the edentulous mandible, after a period of up to 10 years of clinical function.

Material and methods

Thirty patients were treated with four implants each placed interforaminally and provisionally restored within 1 week. Radiographic bone levels, condition of the peri‐implant mucosa, implant survival and success were recorded annually from implant insertion (baseline) up to 10 years after final restoration.

Results

A total of 120 Xi VE S plus implants were placed in the interforaminal region. A significant coronal bone loss of 1.80 mm (SD ± 0.65) was recorded within the first 8 years of function (P < 0.001). Within the next years no further significant increase of bone resorption was observed. The mean values of the plaque, calculus, bleeding and mucosal indices and probing depth remained low throughout this period. All implants were inserted with an insertion torque of more than 32 N cm. Two losses (1.7%) occurred prior to permanent restoration (1 and 3 months post‐insertion), resulting in a survival rate of 98.3% over the entire observation period. Four implants were recorded as failures due to excessive bone resorption, resulting in an overall success rate of 95%.

Conclusions

The results of this study indicate that in selected patients immediate restoration of dental implants in the edentulous mandible will achieve a clinically predictable outcome.
A combination of functionally different plant traits provides a means to quantitatively predict a broad range of species assemblages in NW Europe
Authors: Douma J. C. , Aerts R. , Witte J. P. M. , Bekker R. M. , Kunzmann D. , Metselaar K. , van Bodegom P. M.
Published: September 2011

Assembly theory predicts that filtering processes will select species by their attributes to build a community. Some filters increase functional similarity among species, while others lead to dissimilarity. Assuming converging processes to be dominant within habitats, we tested in this study whether species assemblages across a wide range of habitats can be distinguished quantitatively by their mean trait compositions. In addition, we investigated how many and which traits are needed to describe the differences between species assemblages best. The approach has been applied on a dataset that included 12 plant traits and 7644 vegetation relevés covering a wide range of habitats in the Netherlands. We demonstrate that due to the dominant role of converging processes 1) the functional composition can explain up to 80% of the floristic differences between species assemblages using seven plant traits, showing that plant trait combinations provide a powerful tool for predicting the occurrence of species assemblages across different habitats; 2) to achieve a high performance, traits should be taken from different strategy components, i.e. traits that are functionally orthogonal, which does not necessarily coincide with low trait‐trait correlations; 3) the different strategy components identified in this study correspond to the strategy components of some conventional plant ecological strategy schemes (PESS) – schemes to describe the variation between individual species. However, some PESS merge traits into one strategy component that are shown to be functionally different when predicting species assemblages. If such PESS is used to predict assemblages, this leads to a loss in predictive capacity. Potentially, our new approach is globally applicable to quantify community assembly patterns. However this needs to be tested.
Geographic origin and past climatic experience influence the response to late spring frost in four common grass species in central Europe
Authors: Kreyling Juergen , Thiel Daniel , Simmnacher Katrin , Willner Evelin , Jentsch Anke , Beierkuhnlein Carl
Published: September 2011

Late spring frost events can affect vegetation. The response of grassland species, however, is generally unknown. We explore the late‐frost sensitivity of four common European grass species and investigate whether these species exhibit local adaptations to late frost on a continental scale and whether past climatic experience influences late frost sensitivity.

Ecotypes of Arrhenatherum elatius, Alopecurus pratensis, Festuca pratensis, and Holcus lanatus from Spain, Italy, Bulgaria, Hungary, Sweden and Germany were exposed to late frost after drought and warming manipulations in the preceding growing season in a common garden experiment.

Late frost reduced the productivity of the grasses on average by 20%. Ecotypes differed in their late‐frost sensitivity in three of the four species and local adaptations to late frost were identified. Previous exposure to drought and warming caused differences in late‐frost sensitivity in some cases.

The impact of late frost events may increase in a warmer world due to an earlier onset of growing and no change in timing of late frost events. The history of climatic exposure can alter the performance of plants, possibly through epigenetic mechanisms. Based on the complex response pattern observed, a maximization of genetic diversity is proposed as a promising adaptation strategy against climate change.
Two signal models in innate immunity
Authors: Fontana Mary F. , Vance Russell E.
Published: September 2011

Summary:  Two‐signal models have a rich history in immunology. In the classic two‐signal model of T‐cell activation, signal one consists of engagement of the T‐cell receptor by antigen/major histocompatibility complex, whereas signal two arises from costimulatory ligands on antigen‐presenting cells. A requirement for two independent signals helps to ensure that T‐cell responses are initiated only in response to bona fide infectious threats. Our studies have led us to conclude that initiation of innate immune responses to pathogens also often requires two signals: signal one is initiated by a microbe‐derived ligand, such as lipopolysaccharide (LPS) or flagellin, whereas signal two conveys additional contextual information that often accompanies infectious microbes. Although signal one alone is sufficient to initiate many innate responses, certain responses—particularly ones with the potential for self‐damage—require two signals for activation. Many of our studies have employed the intracellular bacterial pathogen Legionella pneumophila, which has been established as a valuable model for understanding innate immune responses. In this review, we discuss how the innate immune system integrates multiple signals to generate an effective response to L. pneumophila and other bacterial pathogens.
Mitoxosome: a mitochondrial platform for cross‐talk between cellular stress and antiviral signaling
Authors: Tal Michal Caspi , Iwasaki Akiko
Published: September 2011

Summary:  Evidence is accumulating that the mitochondria form an integral platform from which innate signaling takes place. Recent studies revealed that the mitochondria are shaping the innate response to intracellular pathogens, and mitochondrial function is modulating and being modulated by innate immune signaling. Further, cell biologic analyses have uncovered the dynamic relocalization of key components involved in cytosolic viral recognition and signaling to the mitochondria, as well as the mobilization of mitochondria to the sites of viral replication. In this review, we provide an integrated view of how cellular stress and signals following cytosolic viral recognition are intimately linked and coordinated at the mitochondria. We incorporate recent findings into our current understanding of the role of mitochondrial function in antiviral immunity and suggest the existence of a ‘mitoxosome’, a mitochondrial oxidative signalosome where multiple pathways of viral recognition and cellular stress converge on the surface of the mitochondria to facilitate a coordinated antiviral response.
Intracellular sensors of extracellular bacteria
Authors: Clarke Thomas B. , Weiser Jeffrey N.
Published: September 2011

Summary:  Initial recognition of bacteria by the innate immune system is thought to occur primarily by germline‐encoded pattern recognition receptors (PRRs). These receptors are present in multiple compartments of host cells and are thus capable of surveying both the intracellular and extracellular milieu for bacteria. It has generally been presumed that the cellular location of these receptors dictates what type of bacteria they respond to: extracellular bacteria being recognized by cell surface receptors, such as certain Toll‐like receptors, and bacteria that are capable of breaching the plasma membrane and entering the cytoplasm, being sensed by cytoplasmic receptors, including the Nod‐like receptors (NLRs). Increasingly, it is becoming apparent that this is a false dichotomy and that extracellular bacteria can be sensed by cytoplasmic PRRs and this is crucial for controlling the levels of these bacteria. In this review, we discuss the role of two NLRs, Nod1 and Nod2, in the recognition of and response to extracellular bacteria.
Molecular mechanisms of inflammasome activation during microbial infections
Authors: Broz Petr , Monack Denise M.
Published: September 2011

Summary: The innate immune system plays a crucial role in the rapid recognition and elimination of invading microbes. Detection of microbes relies on germ‐line encoded pattern recognition receptors (PRRs) that recognize essential bacterial molecules, so‐called pathogen‐associated molecular patterns (PAMPs). A subset of PRRs, belonging to the NOD‐like receptor (NLR) and the PYHIN protein families, detects viral and bacterial pathogens in the cytosol of host cells and induces the assembly of a multi‐protein signaling platform called the inflammasome. The inflammasome serves as an activation platform for the mammalian cysteine protease caspase‐1, a central mediator of innate immunity. Active caspase‐1 promotes the maturation and release of interleukin‐1β (IL‐1β) and IL‐18 as well as protein involved in cytoprotection and tissue repair. In addition, caspase‐1 initiates a novel form of cell death called pyroptosis. Here, we discuss latest advances and our insights on inflammasome stimulation by two model intracellular pathogens,Francisella tularensisandSalmonella typhimurium. Recent studies on these pathogens have significantly shaped our understanding of the molecular mechanisms of inflammasome activation and how microbes can evade or manipulate inflammasome activity. In addition, we review the role of the inflammasome adapter ASC in caspase‐1 autoproteolysis and new insights into the structure of the inflammasome complex.
Deregulated inflammasome signaling in disease
Authors: Lamkanfi Mohamed , Walle Lieselotte Vande , Kanneganti Thirumala‐Devi
Published: September 2011

Summary:  Inflammasomes are multi‐protein complexes that sense microbial molecules and endogenous danger signals in intracellular compartments. Inflammasome assembly results in caspase‐1 activation, which in turn drives maturation and secretion of the pro‐inflammatory cytokines interleukin 1β (IL‐1β) and IL‐18, and induces pyroptosis to eliminate the infectious agent. The importance of inflammasomes in regulating immune responses was recognized with the discovery of polymorphisms in genes encoding inflammasome components and their linkage to aberrant production of IL‐1β and IL‐18 in autoimmune and hereditary periodic fevers syndromes. We review the current knowledge on the role of inflammasomes in regulating innate and adaptive immune responses with an emphasis on the role of these immune complexes in autoinflammatory disorders and autoimmune diseases such as colitis, type I diabetes, multiple sclerosis and vitiligo.
Caspase‐1‐induced pyroptotic cell death
Authors: Miao Edward A. , Rajan Jayant V. , Aderem Alan
Published: September 2011

Summary:  Programmed cell death is a necessary part of development and tissue homeostasis enabling the removal of unwanted cells. In the setting of infectious disease, cells that have been commandeered by microbial pathogens become detrimental to the host. When macrophages and dendritic cells are compromised in this way, they can be lysed by pyroptosis, a cell death mechanism that is distinct from apoptosis and oncosis/necrosis. Pyroptosis is triggered by Caspase‐1 after its activation by various inflammasomes and results in lysis of the affected cell. Both pyroptosis and apoptosis are programmed cell death mechanisms but are dependent on different caspases, unlike oncosis. Similar to oncosis and unlike apoptosis, pyroptosis results in cellular lysis and release of the cytosolic contents to the extracellular space. This event is predicted to be inherently inflammatory and coincides with interleukin‐1β (IL‐1β) and IL‐18 secretion. We discuss the role of distinct inflammasomes, including NLRC4, NLRP3, and AIM2, as well as the role of the ASC focus in Caspase‐1 signaling. We further review the importance of pyroptosis in vivo as a potent mechanism to clear intracellular pathogens.
The machinery of Nod‐like receptors: refining the paths to immunity and cell death
Authors: Saleh Maya
Published: September 2011

Summary:  One of the fundamental aspects of the innate immune system is its capacity to discriminate between self and non‐self or altered self, and to quickly respond by eliciting effector mechanisms that act in concert to restore normalcy. This capacity is determined by a set of evolutionarily conserved pattern recognition receptors (PRRs) that sense the presence of microbial motifs or endogenous danger signals, including tissue damage, cellular transformation or metabolic perturbation, and orchestrate the nature, duration and intensity of the innate immune response. Nod‐like receptors (NLRs), a group of intracellular PRRs, are particularly essential as evident by the high incidence of genetic variations in their genes in various diseases of homeostasis. Here, I overview the signaling mechanisms of NLRs and discuss the mounting evidence of evolutionary conservation between their pathways and the cell death machinery. I also describe their effector functions that link the sensing of danger to the induction of inflammation, autophagy or cell death.
Peptidoglycan: a critical activator of the mammalian immune system during infection and homeostasis
Authors: Sorbara Matthew T. , Philpott Dana J.
Published: September 2011

Summary:  Peptidoglycan is a conserved structural component of the bacterial cell wall with molecular motifs unique to bacteria. The mammalian immune system takes advantage of these properties and has evolved to recognize this microbial associated molecular pattern. Mammals have four secreted peptidoglycan recognition proteins, PGLYRP‐1‐4, as well as two intracellular sensors of peptidoglycan, Nod1 and Nod2. Recognition of peptidoglycan is important in initiating and shaping the immune response under both homeostatic and infection conditions. During infection, peptidoglycan recognition drives both cell‐autonomous and whole‐organism defense responses. Here, we examine recent advances in the understanding of how peptidoglycan recognition shapes mammalian immune responses in these diverse contexts.
Recognition of nucleic acids by pattern‐recognition receptors and its relevance in autoimmunity
Authors: Kawasaki Takumi , Kawai Taro , Akira Shizuo
Published: September 2011

Summary:  Host cells trigger signals for innate immune responses upon recognition of conserved structures in microbial pathogens. Nucleic acids, which are critical components for inheriting genetic information in all species including pathogens, are key structures sensed by the innate immune system. The corresponding receptors for foreign nucleic acids include members of Toll‐like receptors, RIG‐I‐like receptors, and intracellular DNA sensors. While nucleic acid recognition by these receptors is required for host defense against the pathogen, there is a potential risk to the host of self‐nucleic acids recognition, thus precipitating autoimmune and autoinflammatory diseases. In this review, we discuss the roles of nucleic acid‐sensing receptors in guarding against pathogen invasion, discriminating between self and non‐self, and contributing to autoimmunity and autoinflammatory diseases.
dsRNA sensors and plasmacytoid dendritic cells in host defense and autoimmunity
Authors: Wang Yaming , Swiecki Melissa , McCartney Stephen A. , Colonna Marco
Published: September 2011

Summary:  The innate immune system detects viruses through molecular sensors that trigger the production of type I interferons (IFN‐I) and inflammatory cytokines. As viruses vary tremendously in size, structure, genomic composition, and tissue tropism, multiple sensors are required to detect their presence in various cell types and tissues. In this review, we summarize current knowledge of the diversity, specificity, and signaling pathways downstream of viral sensors and ask whether two distinct sensors that recognize the same viral component are complementary, compensatory, or simply redundant. We also discuss why viral sensors are differentially distributed in distinct cell types and whether a particular cell type dominates the IFN‐I response during viral infection. Finally, we review evidence suggesting that inappropriate signaling through viral sensors may induce autoimmunity. The picture emerging from these studies is that disparate viral sensors in different cell types form a dynamic and integrated molecular network that can be exploited for improving vaccination and therapeutic strategies for infectious and autoimmune diseases.
RIG‐I‐like receptors: cytoplasmic sensors for non‐self RNA
Authors: Kato Hiroki , Takahasi Kiyohiro , Fujita Takashi
Published: September 2011

Summary:  Viral infection results in the generation of non‐self RNA species in the cells, which is recognized by retinoic acid inducible gene‐I‐like receptors (RLRs), and initiates innate antiviral responses, including the production of proinflammatory cytokines and type I interferon. In this review, we summarize reports on virus‐specificity of RLRs, structures of non‐self RNA patterns, structural biology of RLRs, and the signaling adapter molecules involved in antiviral innate immunity.
The PYHIN protein family as mediators of host defenses
Authors: Schattgen Stefan A. , Fitzgerald Katherine A.
Published: September 2011

Summary:  The innate immune response is the first line of defense against infection and relies on the ability of immune cells to detect the presence of infection through germline‐encoded pattern recognition receptors. These include the Toll‐like receptors, the retinoic acid inducible gene‐like receptors, the nucleotide oligomerization domain‐like receptors, and a number of DNA‐sensing molecules. Members of the PYHIN protein family have recently emerged as sensors of microbial DNA. PYHIN proteins bind microbial DNA and form caspase‐1‐activating inflammasomes (AIM2) or drive type I IFN gene transcription (IFI16). Here, we review these discoveries and highlight the emerging role of the PYHIN protein family in mammalian host defenses.
Hepatocytes produce tumor necrosis factor‐α and interleukin‐6 in response to Porphyromonas gingivalis
Authors: Takano M. , Sugano N. , Mochizuki S. , Koshi R. N. , Narukawa T. S. , Sawamoto Y. , Ito K.
Published: September 2011

Takano M, Sugano N, Mochizuki S, Koshi RN, Narukawa TS, Sawamoto Y, Ito K. Hepatocytes produce tumor necrosis factor‐α and interleukin‐6 in response to Porphyromonas gingivalis. J Periodont Res; 2012; 47: 89–94. © 2011 John Wiley & Sons A/S

Background and Objective:  The liver plays a major role in clearing systemic bacterial infections. In addition, inflammatory cytokines produced in the liver play a critical role in systemic cytokine levels. The aim of this study was to investigate the production of tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) by hepatocytes in response to periodontal pathogens.

Material and Methods:  The mouse hepatic carcinoma cell line Hepa‐1.6 and the mouse macrophage‐like cell line RAW 264 were co‐cultured in Transwell insert plates. Cells were stimulated with bacterial extracts prepared from Porphyromonas gingivalis and the induction of TNF‐α and IL‐6 was measured using real‐time PCR and ELISA.

Results:  After stimulation with bacteria, the induction of TNF‐α and IL‐6 was observed in RAW 264 cells and Hepa‐1.6 cells. Significant reduction of TNF‐α mRNA expression in Hepa‐1.6 cells was observed after treatment with antibody to TNF‐α.

Conclusion:  The results obtained in the present study show that P. gingivalis extract induces TNF‐α and IL‐6 in an in vitro liver model and that macrophage‐derived TNF‐α mediates the induction of TNF‐α in hepatocytes.
Early microbial succession in redeveloping dental biofilms in periodontal health and disease
Authors: Teles F. R. , Teles R. P. , Uzel N. G. , Song X. Q. , Torresyap G. , Socransky S. S. , Haffajee A. D.
Published: September 2011

Teles FR, Teles RP, Uzel NG, Song XQ, Torresyap G, Socransky SS, Haffajee AD. Early microbial succession in redeveloping dental biofilms in periodontal health and disease. J Periodont Res 2012; 47: 95–104. © 2011 John Wiley & Sons A/S

Background and Objective:  The development of dental biofilms after professional plaque removal is very rapid. However, it is not clear whether most bacterial species return at similar rates in periodontally healthy and periodontitis subjects or if there are differences in bacterial recolonization between supragingival and subgingival biofilms in periodontal health and disease.

Material and Methods:  Supragingival and subgingival plaque samples were taken separately from 28 teeth in 38 healthy and 17 periodontitis subjects immediately after professional cleaning. Samples were taken again from seven teeth in randomly selected quadrants after 1, 2, 4 and 7 d of no oral hygiene and analyzed using checkerboard DNA–DNA hybridization. The percentage of DNA probe counts were averaged within subjects at each time‐point. Ecological succession was determined using a modified moving‐window analysis.

Results:  Succession in supragingival biofilms from subjects with periodontitis and from healthy individuals was similar. At 1 d, Streptococcus mitis and Neisseria mucosa showed increased proportions, followed by Capnocytophaga gingivalis, Eikenella corrodens, Veillonella parvula and Streptococcus oralis at 1–4 d. At 4–7 d, Campylobacter rectus, Campylobacter showae, Prevotella melaninogenica and Prevotella nigrescens became elevated. Subgingival plaque redevelopment was slower and very different from supragingival plaque redevelopment. Increased proportions were first observed for S. mitis, followed by V. parvula and C. gingivalis and, at 7 d, by Capnocytophaga sputigena and P. nigrescens. No significant increase in the proportions of periodontal pathogens was observed in any of the clinical groups or locations.

Conclusion:  There is a defined order in bacterial species succession in early supragingival and subgingival biofilm redevelopment after professional cleaning.
Correlation of cytomegalovirus and human herpesvirus 7 with CD3+ and CD3+CD4+ cells in chronic periodontitis patients
Authors: Thomasini R. L. , Bonon S. H. , Durante P. , Costa S. C. B.
Published: September 2011

Thomasini RL, Bonon SH, Durante P, Costa SCB. Correlation of cytomegalovirus and human herpesvirus 7 with CD3

+

and CD3

+

CD4

+

cells in chronic periodontitis patients. J Periodont Res 2012; 47: 114–120. © 2011 John Wiley & Sons A/S

Background and Objective:  Human chronic periodontitis is an inflammatory process characterized by dense accumulation of immune cells in the periodontal tissue. The periodontitis can lead to loss of teeth in the patient and the pathogenesis of this disease is not completely known. This study tested the hypothesis that chronic periodontitis‐affected sites can harbor betaherpesviruses and that viruses are linked to a profile of the inflammatory infiltrate.

Material and Methods:  Biopsies of periodontal tissue were taken from periodontitis‐affected patients and from healthy subjects. Immunohistochemistry was performed to count CD19+ B cells, CD3+ total T cells, T‐CD4+ and T‐CD8+ cell subsets, and PCR was performed to detect cytomegalovirus and human herpesvirus 6 and 7 in the samples. One slide of each sample was stained with Giemsa for histopathological examination and to evaluate the quality of the cellular infiltrate.

Results:  As expected, tissues collected from healthy subjects presented no significant level of inflammatory infiltration and were therefore excluded from immunostaining procedures. Results showed that CD19+ B cells were in higher number than CD3+ T cells in the periodontitis‐affected tissue, but this was not statistically significant. The T‐CD4+ lymphocyte subset was significantly higher than the T‐CD8+ lymphocyte subset (p = 0.004) in the samples. Cytomegalovirus and human herpesvirus 7 were found at periodontitis‐affected sites, but not in tissue collected from healthy subjects (p = 0.04 and p = 0.04, respectively). Human herpesvirus 6 was rarely detected. We found a correlation between cytomegalovirus and lower CD19+/CD3+ ratios (ratio < 0.9, p = 0.003) and between human herpesvirus 7 and lower CD19+/CD3+ ratios (ratio < 0.9, p = 0.003) and higher CD4+/CD8+ ratios (ratio > 1.1, p = 0.002).

Conclusion:  This study shows that cytomegalovirus and human herpesvirus 7 can be present at periodontitis‐affected sites but are uncommon at healthy periodontal sites. Moreover, our data suggest that cytomegalovirus can be related to an inflammatory infiltrate with predominance of CD3+ T cells, whereas human herpesvirus 7 can be associated with an infiltrate with predominance of T‐CD4+ cells. However, further studies are necessary to support this hypothesis. Herpesviruses could play a role in human chronic periodontitis by modulation of the T cell response.
Molecular pathways involved in seasonal body weight and reproductive responses governed by melatonin
Authors: Barrett Perry , Bolborea Matei
Published: September 2011

Abstract:  Seasonal mammals typically of temperate or boreal habitats use the predictable annual cycle of daylength to initiate a suite of physiological and behavioural changes in anticipation of adverse environmental winter conditions, unfavourable for survival and reproduction. Daylength is encoded as the duration of production of the pineal hormone melatonin, but how the melatonin signal is decoded has been elusive. From the studies carried out in birds and mammals together with the advent of technologies such as microarray analysis of gene expression, progress has been achieved to demystify how seasonal physiology is regulated in response to the duration of melatonin signalling. The critical tissue for the action of melatonin is the pars tuberalis (PT) where melatonin receptors are located. At the molecular level, regulation of cyclic adenosine monophosphate (cAMP) signalling in this tissue is likely to be a key event for melatonin action, either an acute inhibitory action or sensitization of this pathway by prolonged stimulation of melatonin receptors reflecting durational melatonin presence. Melatonin action at the PT has been shown to have both positive and negative effects on gene transcription, incorporating components of the circadian clock as part of the mechanism of decoding the melatonin signal and regulating thyrotrophin‐stimulating hormone (TSH) expression, a key output hormone of the PT. Microarray analysis of gene expression of PT tissue exposed to long and short photoperiods has identified important new genes that may be regulated by melatonin and contributing to the seasonal regulation of TSH production by this tissue. In the brain, tanycytes lining the third ventricle of the hypothalamus and regulation of thyroid hormone synthesis by PT‐derived TSH in these cells are now established as an important component of the pathway leading to seasonal changes in physiology. Beyond the tanycyte, identified changes in gene expression for neuropeptides, receptors and other signalling molecules pinpoint some of the areas of the brain, the hypothalamus in particular, that are likely to be involved in the regulation of seasonal physiology.
Interleukin‐6 autocrine signaling mediates melatonin MT1/2 receptor‐induced STAT3 Tyr705 phosphorylation
Authors: Lau Winnie W. I. , Ng Johnson K. Y. , Lee Maggie M. K. , Chan Anthony S. L. , Wong Yung H.
Published: September 2011

Abstract:  Melatonin receptors have previously been shown to elicit cellular signaling through the hematopoietic‐specific G protein, G16. In the present study, we show that this functional coupling elicited biphasic stimulatory phosphorylation on STAT3 in recombinant MT1/Gα16 cells and native Jurkat T cells (endogenously expressing MT1 and Gα16), with maximal Ser727 phosphorylation occurring at 15 min, while marked Tyr705 phosphorylation became detectable only upon agonist treatment for 4 hr or more. By employing signal transducer and activator of transcription 3 (STAT3) phosphorylation‐resistant mutants (STAT3‐Y705F and STAT3‐S727A), we further showed that the receptor‐mediated STAT3 phosphorylations at Ser727 and Tyr705 were independent of each other. Results obtained from fractionation of 2‐IMT‐induced cells revealed that the Ser727 and Tyr705 phosphorylations were spatially distinct, with the former mainly situated in mitochondria and cytosol, while the latter was predominantly located in the nucleus. Further experiments revealed that the agonist‐induced STAT3 phosphorylation at Tyr705 was significantly suppressed by pretreatment with cycloheximide (a ribosome inhibitor), suggesting that de novo protein synthesis might play a critical role for this response. Using conditioned media obtained from 2‐IMT‐treated MT1/Gα16 cells, multiplex immunoassays revealed that prolonged agonist treatment led to elevated productions of IL‐6, GM‐CSF and CXCL‐8. Antibody against IL‐6, but not those for GM‐CSF and CXCL‐8, effectively abolished the agonist‐induced STAT3 Tyr705 phosphorylation, suggesting the involvement of IL‐6 in melatonin receptor‐mediated STAT3 activation. Our results demonstrate that melatonin receptor/Gα16 coupling is capable of triggering the production of cytokines including IL‐6, and this autocrine loop may account for the subsequent STAT3 phosphorylation at Tyr705.
Targeted 307 nm UVB‐phototherapy in psoriasis. A pilot study comparing a 307 nm excimer light with topical dithranol
Authors: Wollina Uwe , Koch André , Scheibe Armin , Seme Bernd , Streit Ingolf , Schmidt Wolf‐Dieter
Published: September 2011

Background

Phototherapy is a cornerstone in treatment of moderate‐to‐severe psoriasis. Narrow‐band UVB has been shown to be a potent therapeutic tool. To reduce the potential carcinogenic risk, targeted phototherapy has been developed using excimer lasers or excimer light devices (ELD).

Objective

The role of excimer light therapy in practice and modes of action are not completely understood. We wanted to investigate a 307 nm ELD for plaque psoriasis in comparison with topical dithranol therapy twice daily.

Methods

We conducted a pilot trial in 21 adult patients with moderate plaque‐type psoriasis. Two target lesions of comparable size and plaque‐modified Psoriasis Activity and Severity Index (PSI) scores were selected. Lesion A was treated three times using a newly developed 307 nm ELD. Lesion B was treated twice daily with dithranol ointment. The mean period of treatment was 9 days. Clinical evaluation included PSI scores, safety, time needed to treat, and patient's satisfaction. In addition, fluorescence‐remission imaging technique was used for objective evaluation.

Results

Both treatments improved the PSI score (mean 3.0 points). The treatments were safe but ELD was more convenient for patients. The time needed to treat the target lesion was significantly shorter with ELD. Targeted UVB therapy normalized NADH fluorescence in lesional skin.

Conclusions

The 307 nm excimer light therapy for plaque type psoriasis was equipotent to twice daily topical dithranol. Efficacy, safety, and convenience suggest that targeted UVB therapy with quasi monochromatic light is a new useful treatment option for patients with limited psoriatic plaques.
Disturbance history of an old‐growth sub‐alpine Picea abies stand in the Bohemian Forest, Czech Republic
Authors: Svoboda Miroslav , Janda Pavel , Nagel Thomas A. , Fraver Shawn , Rejzek Jan , Bače Radek
Published: September 2011

Questions

What historical natural disturbances have shaped the structure and development of an old‐growth, sub‐alpine Picea abies forest? Are large‐scale, high‐severity disturbances (similar to the recent windthrow and bark beetle outbreaks in the region) within the historical range of variability for this forest ecosystem? Can past disturbances explain the previously described gradient in stand structure that had been attributed to an elevation gradient?

Location

Šumava National Park (the Bohemian Forest) of the southwest Czech Republic.

Methods

We reconstructed the site's disturbance history using dendroecological methods in a 20‐ha study plot, established to span an elevation gradient. Growth patterns of 400 increment cores were screened for: (1) abrupt increases in radial growth indicating mortality of a former canopy tree and (2) rapid early growth rates indicating establishment in a former canopy gap.

Results

Spatial and temporal patterns of canopy accession varied markedly over the 20‐ha study area, resulting in disturbance pulses that corresponded to an elevation gradient. On the lower slope of the plot, the majority of the trees reached the canopy during two pulses (1770–1800 and 1820–1840), while most trees on the upper slope accessed the canopy in one pulse (1840–1860). Historically documented windstorms roughly coincide with peaks in our disturbance reconstruction.

Conclusions

Our study provides strong evidence that these forests were historically shaped by infrequent, moderate‐ to high‐severity natural disturbances. Our methods, however, could not definitively identify the agent(s) of these disturbances. Nevertheless, the recent mid‐1990s windstorm and the ensuing spruce bark beetle outbreak may provide an analogue for past disturbance, as the duration and severity of these events could easily explain past patterns of growth response and recruitment in our results. Thus, it seems reasonable to assume the interaction of windstorms and bark beetles seen in the contemporary landscape has occurred historically. Finally, our results suggest that the previously documented elevation gradient in forest structure may not be related to elevation per se (lower temperatures and shorter growing season) but rather to changes in disturbance severity mediated by elevation.