Morphological and morphometric features of sacral hiatus and its clinical significance in caudal epidural anaesthesia.

BACKGROUND: Caudal epidural block (CEB) failure or complications are not unheard even among experienced anaesthesiologists and are usually due to sacral hiatus (SH) anatomy variations. The aim of the present study is to observe, record and analyse important anatomical features of SH and correlate them with potential CEB limitations. MATERIALS AND METHODS: The SH of 155 complete and undamaged Greek adult dry sacra of known sex were included in the study. Three non-metric (shape of SH and location of hiatal apex and base in relation to level of sacral/coccygeal vertebra) and five metric parameters (height of the SH, transverse width of the SH at the base, anteroposterior diameter of the SH at the level of its apex and the distance from the sacral apex and base to the upper border of S2 foramina) were evaluated. RESULTS: Inverted U (34.83%) and inverted V (26.45%) were the commonest shapes. Hiatal apex and base were most commonly related to the level of S4 (78.70%) and S5 vertebra (89.03%), respectively. Mean height, depth and intercornual distance were 19.05 ± 8.65 mm, 5.39 ± 1.84 mm and 12.41 ± 3.16 mm, respectively, whereas mean distance between the upper border of S2 foramen and the apex and base of the SH were 46.34 mm and 63.48 mm, respectively. Anatomical variations of SH that might be responsible for CEB failure, such as elongated SH, absence of SH, complete dorsal wall agenesis of sacral canal and narrowing (< 3 mm) at the apex of SH were found in 17.43% of sacra (male 10.94% and female 25.22%). CONCLUSIONS: This study suggests a potential risk of failure of CEB in Greek patients, especially in females, which should be kept in mind while giving caudal epidural anaesthesia.

A qualitative study examining transgender people's attitudes towards having a child to whom they are genetically related and pursuing fertility treatments in Greece.

BACKGROUND: Advances in biomedical technologies permit transgender individuals not only to achieve gender transition but also to experience parenthood. Little is known about this topic in Greece, which, although a traditionally conservative country, is changing at the legal level towards a greater recognition of transgender people's rights. This study aimed to investigate transgender people's attitudes towards having a child to whom they are genetically related and pursuing fertility treatments in Greece. METHODS: This is a prospective qualitative study conducted with adult individuals who identified as transgender men or transgender women between April 2019 and March 2020. Individual in-depth qualitative interviews were conducted with 12 participants. The interviews were carried out in person and were digitally recorded and transcribed verbatim. We performed a thematic analysis of the data. RESULTS: The thematic data analysis resulted in the identification of themes that represent key barriers to pursuing fertility preservation or the use of assisted reproductive technology. Six major themes were clearly present in the findings (lack of adequate information and counseling, worsening gender dysphoria, increased discrimination against transgender people due to the rise of extreme far-right populism, low parental self-efficacy, high costs, and a less-than-perfect legal framework). Moreover, diverse cases were examined, and minor themes, such as the symbolic value of the uterus and pregnancy, the relationship between the type of gender transition and willingness to pursue fertility treatments, and transgender people's adherence to heteronormative patterns in the context of reproduction, were identified. Various reasons for transgender people's differing degrees of desire for parenthood were identified. CONCLUSION: Our findings demonstrated contextual factors as well as factors related to transgender people themselves as barriers to pursuing transgender parenthood. Most aspects of our findings are consistent with those of previous research. However, some aspects of our findings (regarding aggressive behaviors and economic instability) are specific to the context of Greece, which is characterized by the rise of extreme far-right populism due to the decade-long Greek economic crisis and a deeply conservative traditionalist background. In that regard, the participants highlighted the (perceived as) less-than-perfect Greek legislation on transgender people's rights as a barrier to transgender (biological) parenthood.

Research findings on Greek forensic patients found not guilty by reason of insanity. A juxtaposition of patients who committed a criminal offense during their first psychotic episode with those who did so later in the course of their illness.

The aim of this study was to compare the baseline characteristics (demographic, psychiatric-psychopathological and legal) among Greek forensic patients found not guilty by reason of insanity. The first step of this approach being differentiating patients who committed a criminal offense during their first psychotic episode from the ones who did so later in the course of their illness. All patients were hospitalized in the Department of Forensic Psychiatry (DFP) of the Psychiatric Hospital of Thessaloniki (PHT) from January 2015 to January 2020 and were examined in order to be included in the study. The final research sample consisted of 78 patients (70 identifying themselves as males and 8 identifying themselves as females) aged 18 and older, 21 of whom committed a criminal offense during their first psychotic episode (FEP, N = 21) and 57 did so later on in the course of their illness (Course, N = 57). Data were collected from multiple sources and several psychometric tools were used (Mini International Neuropsychiatric Interview-M.I.N·I, Positive And Negative Syndrome Scale-PANSS, Addiction Severity Index-ASI, CAGE Questionnaire, Hostility and Direction of Hostility Questionnaire-HDHQ, Global Assessment of Functioning-GAF and Aggression Questionnaire). Comparing the two groups (FEP vs. Course) we found that patients in FEP were younger, had experienced stressful life events in the last 24 months, committed more serious violent crimes, and more frequently attempted suicide after the crime. Their victims were usually members of their family. The main psychometric disparities between the two groups were found in the "Hostility" score of the Aggression questionnaire, and the items "Criticism of Others" and "Paranoid Hostility" of the HDHQ questionnaire, where patients in FEP scored lower. Patients in FEP scored significantly higher in items P1 (delusions), P4 (excitement), P6 (suspiciousness/persecution) and P7 (hostility) of the PANSS scale. No statistically significant differences were found between the two groups regarding their evaluation with the CAGE, ASI or GAF questionnaires. When comparing the patients' present scores in PANSS scale, the patients in FEP had lower total scores in the Positive and the General Psychopathology subscales. Both groups showed significant improvement during hospitalization in all scales (PANSS & GAF), except for the Negative Subscale of the PANSS scale. Through logistic regression analysis, we found that patients in FEP were younger, more likely to have recently experienced stressful life events and more likely to have assaulted a member of their family. Patients with higher scores in the "Hostility" subscale of the Aggression questionnaire were found to remain at risk for committing a crime during the course of their illness. These findings underline the need to design and develop specialized mental health services in order to identify and treat patients involved in violent crime in a timely and effective manner addressing their multiple needs.

Involuntary psychiatric hospitalization of children and adolescents in Northern Greece: Retrospective epidemiological study and related ethical issues.

The aim of the present study was to investigate epidemiological data on involuntary hospitalization of underage patients in psychiatric settings and illustrate the related ethical issues. The medical records of 131 involuntary psychiatric admissions of children and adolescents ordered by public prosecutor between 2005 and 2014 were examined carefully. The examined variables involved the place of origin, the place of residence of minors after discharge, the length of stay in hospitals, the discharge diagnosis, the rate at which the minors were introduced to police and other authorities before their hospitalization, and the results of the neuropsychological assessment (WISC II). Data were analyzed by SPSS (Statistical Package for the Social Sciences). The mean age of the minors was 14.19 years (Male: Female ratio; 1.6:1). First, a high rate of incidences of compulsory admissions was found [5-year period (2005-2009):(2010-2014) ratio; 1:1.85] most likely due to organizational factors, which, however, could have been avoided in a more patient-oriented healthcare system. It is most likely that the criteria used for making decisions in favor of compulsory admissions were disproportionately (unduly) broad. In parallel, it was observed that, during 2010-2014, despite the increase in the rate of the prosecutor's orders, there was a decrease in the duration of coercive hospitalization of minors in psychiatric departments of hospitals in comparison to the period 2005-2009 [5-year period duration of hospitalization (2005-2009):(2010-2014) ratio; 2.33:1]. Furthermore, family was found likely to wield considerable influence on the decision-making for compulsory admissions. In addition, the effectiveness of a compulsory hospitalization of minors in a child and adolescent psychiatry department was found largely dependent on the type of the underlying mental health problem. In that respect, low rates of recidivism (7.6%) indicated that the measure of involuntary hospitalization was necessary and effective. It was also observed that the short-term removal of the minor from the family environment was a potentially relieving strategy for both the child and the family apart from the need for therapeutic intervention. The paper concludes by highlighting the role of a multi-stakeholder decision-making process (which entails shared decision-making as an integral component of providing mental healthcare to minors) in facilitating a decision about involuntary psychiatric hospitalization that is proportional and respectful to patient autonomy.

Anatomy and clinical significance of sacral variations: a systematic review.

The sacrum is a large trilateral bone located at the base of the vertebral column serving to transfer the body weight from the trunk to the pelvis and lower extremities. Over the years, an abundance of sacral anatomical divergences has been reported, including numerical and/or morphological variations of sacral entities. The majority of these anatomical alternations has been incidentally identified during radiological investigations, surgical procedures or discovered in anatomical, anthropological and forensic research studies. Throughout international literature, however, there is a scarcity of an integrative recording of all known anatomical variations of the sacrum in a single study. This constitutes the objective of the present paper: to provide an exhaustive systematic review of the relevant literature, as well as to thoroughly describe all the recognized deviations of the sacrum structure, while highlighting the aspects of their clinical significance.

Depressive symptoms in inflammatory bowel disease: an extraintestinal manifestation of inflammation?

Depressive symptoms are reported by more than 20% of people with inflammatory bowel disease (IBD), while sleep difficulties and fatigue are even more common. Co-morbid depressive symptoms predict a poor IBD course, including increased risk of relapse and surgery, which is inconsistently improved by psychological treatments. Rather than being distinct systems, there is compelling evidence for bidirectional communication between gut and brain, driven by neural, metabolic, endocrine and inflammatory mediators. An emerging concept is that depressive symptoms may be mechanistically linked to excess inflammation and dysregulation of the gut-brain axis. Given the close link between the intestinal microbiota and host immune responses, patients prone to shifts in their intestinal microbiome, including smokers, those with poor diet and early life stress, may be exposed to exaggerated immune responses. Excess inflammation is associated with brain changes (depressive symptoms, fatigue, sleep difficulties) and worsening gastrointestinal symptoms, which are exacerbated by psychological distress. Equally, treatments both for depressive symptoms and IBD provide opportunities to break this cycle by reducing the causes and effects of inflammation. As well as addressing potential risk factors such as smoking and diet, treatments to alter the microbiome may reduce depressive symptoms. Observational evidence suggests that anti-inflammatory treatments for IBD may improve co-morbid depressive symptoms correlating with reduction in inflammation. With a growing range of treatments targeting inflammation centrally, peripherally and in the gut, IBD provides a unique model to understand the interplay between brain and gut in the pathogenesis of depressive symptoms, both in IBD and in the whole population.

Conium maculatum intoxication: Literature review and case report on hemlock poisoning.

The aim of this paper is to highlight the symptomatology in three Conium maculatum intoxication incidents, one of which was fatal. A number of studies were reviewed in order to update and summarize the relevant literature on the incidence, sociodemographic variables, method of poisoning, pathophysiology, diagnosis, variables associated with survival and fatality, management, and treatment of C. maculatum intoxication as well as the biosynthesis and biological effects of poison hemlock alkaloids. Results show that hemlock poisoning is relatively rare, although incidence varies in different regions, despite its worldwide distribution. Hemlock poisoning is more common in European and especially Mediterranean countries. The majority of the patients are adult males over 38 years of age. The clinical course of hemlock poisoning includes neurotoxicosis, tremor, vomiting, muscle paralysis, respiratory paralysis/failure, rhabdomyolysis, and acute renal failure. The therapeutic management focuses on absorption reduction, close observation for complications, and supportive therapy (especially for respiration). Acute occurrence is severe and life-threatening, but the survival rate is high if treatment is provided promptly. Recovery is rapid, generally taking only a few days.

Concurrent lumbosacral and sacrococcygeal fusion: a rare aetiology of low back pain and coccygodynia?

Sacrum is a triangular bone placed in the base of the spine and formed by the synostosis of five sacral vertebrae (S1-S5). Its upper part is connected with the inferior surface of the body of L5 vertebra forming the lumbosacral joint, while its lower part is connected with the base of the coccyx forming the sacrococcygeal symphysis, an amphiarthrodial joint. The existence of four pairs of sacral fora-mina in both anterior and posterior surface of the sacrum is the most common anatomy. Nevertheless, supernumerary sacral foramina are possible to be created by the synostosis of lumbosacral joint or sacrococcygeal symphysis. We present a case of an osseous cadaveric specimen of the sacrum belonging to a 79-year-old Caucasian woman. A rare variation of the anatomy of the sacrum is reported; in which, the simultaneous fusion of the sacrum with both the L5 vertebra and the coccyx has created six pairs of sacral foramina. This variation should be taken into serious consideration, especially in the domain of radiology, neurosurgery, orthopaedics and spine surgery, because low back pain, coccygodynia and other neurological symptoms may emerge due to mechanical compression. (Folia Morphol 2018; 77, 2: 397-399).

Multi-rate Poisson tree processes for single-locus species delimitation under maximum likelihood and Markov chain Monte Carlo.

MOTIVATION: In recent years, molecular species delimitation has become a routine approach for quantifying and classifying biodiversity. Barcoding methods are of particular importance in large-scale surveys as they promote fast species discovery and biodiversity estimates. Among those, distance-based methods are the most common choice as they scale well with large datasets; however, they are sensitive to similarity threshold parameters and they ignore evolutionary relationships. The recently introduced "Poisson Tree Processes" (PTP) method is a phylogeny-aware approach that does not rely on such thresholds. Yet, two weaknesses of PTP impact its accuracy and practicality when applied to large datasets; it does not account for divergent intraspecific variation and is slow for a large number of sequences. RESULTS: We introduce the multi-rate PTP (mPTP), an improved method that alleviates the theoretical and technical shortcomings of PTP. It incorporates different levels of intraspecific genetic diversity deriving from differences in either the evolutionary history or sampling of each species. Results on empirical data suggest that mPTP is superior to PTP and popular distance-based methods as it, consistently yields more accurate delimitations with respect to the taxonomy (i.e., identifies more taxonomic species, infers species numbers closer to the taxonomy). Moreover, mPTP does not require any similarity threshold as input. The novel dynamic programming algorithm attains a speedup of at least five orders of magnitude compared to PTP, allowing it to delimit species in large (meta-) barcoding data. In addition, Markov Chain Monte Carlo sampling provides a comprehensive evaluation of the inferred delimitation in just a few seconds for millions of steps, independently of tree size. AVAILABILITY AND IMPLEMENTATION: mPTP is implemented in C and is available for download at http://github.com/Pas-Kapli/mptp under the GNU Affero 3 license. A web-service is available at http://mptp.h-its.org . CONTACT: : paschalia.kapli@h-its.org or alexandros.stamatakis@h-its.org or tomas.flouri@h-its.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Greenish-blue gastric content: Literature review and case report on acute copper sulphate poisoning.

A literature review of cases of acute poisoning by copper sulfate was conducted, emphasizing therapeutic interventions, and a new fatality case is reported. Specifically, the relevant literature was reviewed for incidence rates, sociodemographic variables, pathophysiology, diagnosis, prognosis, and therapeutic outcome of copper sulfate poisoning. Results conclude that copper sulfate poisoning incidence varies in different regions. It is rare in western countries, while it is very common in South Asian countries. The majority of patients belong to rural populations and are males in the third decade of their lives. The lethal dose of ingested copper is considered to be 10-20 g; 14-36% of the patients pass away within a few hours of ingestion, while the average hospitalization time is more than 20 days. The clinical features of copper sulfate poisoning include erosive gastropathy, intravascular hemolysis, methemoglobinemia, hepatitis, and acute kidney injury. The therapeutic management focuses on absorption reduction, close observation for complications, supportive therapy, and chelation therapy.

A comparative immunohistochemical investigation of the consequences of chorioamnionitis on the developing human fetal spleen.

INTRODUCTION: The objective of this study was to determine the effects of chorioamnionitis on the extracellular matrix (ECM) structural glycoproteins of the developing human fetal spleen, and their influence on the haematopoiesis and spleen immune system compared to controls. MATERIALS AND METHODS: After elective induced pregnancy termination due to chorioamnionitis or voluntary abortion, paraffin-embedded specimens from the spleen and respective fetal membranes of 90 fetuses were investigated by immunohistochemistry for presence of ECM structural glycoproteins, haematopoietic, and lymphoid cells. Conventional histological examination of the relative fetal membranes was performed. RESULTS: The present results showed no quantitative variations in the expression of the ECM glycoproteins and haematopoietic lineages of the fetal spleen parenchyma at the end of first trimester (in both groups). At the second and third trimesters, acute chorioamnionitis showed a decreased number of the aforementioned proteins, with an increase of granulopoiesis and CD34 progenitor/stem haematopoietic cells. The immune system of the spleen during the third trimester demonstrated a decrease of both B and T lymphocytes, in comparison with controls. CONCLUSIONS: These results suggest that toxins and cytokines generated during chorioamnionitis, seem to influence ECM structural glycoproteins synthesis and release in fetal splenic parenchyma by reducing them, and probably cause further disorders of haematopoiesis and lymphopoiesis.

CoMuS: simulating coalescent histories and polymorphic data from multiple species.

The simultaneous analysis of intra- and interspecies variation is challenging mainly because our knowledge about patterns of polymorphisms where both intra- and interspecies samples coexist is limited. In this study, we present CoMuS (Coalescent of Multiple Species), a multispecies coalescent software that can simulate intra- and interspecies polymorphisms. CoMuS supports a variety of speciation models and demographic scenarios related to the history of each species. In CoMuS, speciation can be accompanied by either instant or gradual isolation between sister species. Sampling may also occur in the past, and thus, we can study simultaneously extinct and extant species. Our software supports both the infinite- and the finite-site model, with substitution rate heterogeneity among sites and a user-defined proportion of invariable sites. We demonstrate the usage of CoMuS in various applications: species delimitation, software testing, model selection and parameter inference involving present-day and ancestral samples, comparison between gradual and instantaneous isolation models, estimation of speciation time between human and chimpanzee using both intra- and interspecies variation. We expect that CoMuS will be particularly useful for studies where species have been separated recently from their common ancestor and phenomena such as incomplete lineage sorting or introgression still occur.

Systematic review: bile acids and intestinal inflammation-luminal aggressors or regulators of mucosal defence?

BACKGROUND: Inflammatory bowel diseases (IBD), comprising Crohn's disease and ulcerative colitis (UC), are chronic conditions attributed to an aberrant immune response to luminal triggers. Recently, published work suggests a pathogenic role for bile acids in this context. AIM: To perform a systematic review of studies investigating the role of bile acids in intestinal inflammation and present potentially relevant clinical implications. METHODS: Pubmed search for English language articles published up to May 2015. Terms used were: 'bile', 'bile acid', 'barrier', 'small bowel injury', 'Crohn's' and 'colitis'. RESULTS: Experimental studies support a variable role for bile acids in intestinal barrier homoeostasis. This may be attributed to different physicochemical properties, variable effects on epithelia and immune cells via bile acids-specific receptors, or through a cross-talk with the gut microbiome. A reduction in the bile acids pool, with lower concentrations of secondary forms, has been recognised for some time in Crohn's disease and associated to ileal dysfunction and bile acids malabsorption. Recent work suggests that these changes, including an increase in sulphated forms, are related to inflammatory activity in both Crohn's disease and UC. The detrimental effects of 'western diet' elements such as emulsifiers and fat, which have been implicated in the development of the current IBD and obesity epidemics, may also be bile acid-mediated. CONCLUSIONS: Although there are only a few observational clinical studies to support an interaction, in vivo human and animal studies support an association between bile acids metabolism, the gut microbiome and intestinal inflammation. This may well prove to have significant diagnostic and therapeutic implications.

De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability.

Schizophrenia is a serious psychiatric disorder with a broadly undiscovered genetic etiology. Recent studies of de novo mutations (DNMs) in schizophrenia and autism have reinforced the hypothesis that rare genetic variation contributes to risk. We carried out exome sequencing on 57 trios with sporadic or familial schizophrenia. In sporadic trios, we observed a ~3.5-fold increase in the proportion of nonsense DNMs (0.101 vs 0.031, empirical P=0.01, Benjamini-Hochberg-corrected P=0.044). These mutations were significantly more likely to occur in genes with highly ranked probabilities of haploinsufficiency (P=0.0029, corrected P=0.006). DNMs of potential functional consequence were also found to occur in genes predicted to be less tolerant to rare variation (P=2.01 × 10(-)(5), corrected P=2.1 × 10(-)(3)). Genes with DNMs overlapped with genes implicated in autism (for example, AUTS2, CHD8 and MECP2) and intellectual disability (for example, HUWE1 and TRAPPC9), supporting a shared genetic etiology between these disorders. Functionally CHD8, MECP2 and HUWE1 converge on epigenetic regulation of transcription suggesting that this may be an important risk mechanism. Our results were consistent in an analysis of additional exome-based sequencing studies of other neurodevelopmental disorders. These findings suggest that perturbations in genes, which function in the epigenetic regulation of brain development and cognition, could have a central role in the susceptibility to, pathogenesis and treatment of mental disorders.

Gingival tissue transcriptomes identify distinct periodontitis phenotypes.

The currently recognized principal forms of periodontitis-chronic and aggressive-lack an unequivocal, pathobiology-based foundation. We explored whether gingival tissue transcriptomes can serve as the basis for an alternative classification of periodontitis. We used cross-sectional whole-genome gene expression data from 241 gingival tissue biopsies obtained from sites with periodontal pathology in 120 systemically healthy nonsmokers with periodontitis, with available data on clinical periodontal status, subgingival microbial profiles, and serum IgG antibodies to periodontal microbiota. Adjusted model-based clustering of transcriptomic data using finite mixtures generated two distinct clusters of patients that did not align with the current classification of chronic and aggressive periodontitis. Differential expression profiles primarily related to cell proliferation in cluster 1 and to lymphocyte activation and unfolded protein responses in cluster 2. Patients in the two clusters did not differ with respect to age but presented with distinct phenotypes (statistically significantly different whole-mouth clinical measures of extent/severity, subgingival microbial burden by several species, and selected serum antibody responses). Patients in cluster 2 showed more extensive/severe disease and were more often male. The findings suggest that distinct gene expression signatures in pathologic gingival tissues translate into phenotypic differences and can provide a basis for a novel classification.

Electrogustometry thresholds, tongue tip vascularization, and density and morphology of the fungiform papillae in diabetes.

OBJECTIVES: The aim of this study was to investigate, in parallel, changes in electrogustometric (EGM) thresholds, the morphology and density of the fungiform papillae (fPap), and the shape and density of the vessels at the tip of the human tongue in patients with diabetes mellitus (DM). METHODOLOGY: In 36 patients (19 females, 17 males; 12 subjects with type 1 DM and 24 subjects with type 2 DM), we recorded bilateral EGM-thresholds at the areas innervated by the chorda tympani, the glossopharyngeal nerves, and the greater petrosal nerves. We examined the morphology and density of the fPap and blood vessel density and morphology at the tip of the tongue with contact endoscopy (CE). A group of 36 healthy, age-matched, non-smoking individuals served as controls. RESULTS: The fPap density measured by CE was significantly (p < 0.05) reduced in DM compared to control groups. EGM-thresholds were significantly higher in the DM group than in the control group (p < 0.05). Gender did not have a significant impact on CE and EGM findings within the DM group. Body mass index did not significantly affect EGM-thresholds or the morphology and vascularization of fPap. CONCLUSION: These results suggested that DM significantly reduced gustatory function, based on EGM, and impaired the gustatory anatomical structures, based on CE. Both EGM and CE may be useful in clinical settings to monitor taste disorders in patients with DM.

Immature malignant sacrococcygeal teratoma: case report and review of the literature.

Immature malignant sacrococcygeal teratoma (SCT) is a rare tumor, deriving from the three germinal layers and is found in the sacrococcygeal region. It is the most frequent site of teratomas in the fetus. A nut-brown, solid tumor with cystic areas with a ten-cm diameter is reported in the sacrococcygeal region of a female fetus of 23 weeks and with a weight of 308 g. The ultrasound and pathology evaluations revealed characteristics of an immature malignant SCT. The incidence of this tumor type is one in 35,000 to 40,000 live births and females are four times more likely to be affected than males. Sacrococcygeal and cervical teratomas can be diagnosed by prenatal ultrasound and magnetic resonance imaging (MRI). Teratomas are considered an interesting field for research.

Molecular differences between chronic and aggressive periodontitis.

The 2 major forms of periodontitis, chronic (CP) and aggressive (AgP), do not display sufficiently distinct histopathological characteristics or microbiological/immunological features. We used molecular profiling to explore biological differences between CP and AgP and subsequently carried out supervised classification using machine-learning algorithms including an internal validation. We used whole-genome gene expression profiles from 310 'healthy' or 'diseased' gingival tissue biopsies from 120 systemically healthy non-smokers, 65 with CP and 55 with AgP, each contributing with ≥ 2 'diseased' gingival papillae (n = 241; with bleeding-on-probing, probing depth ≥ 4 mm, and clinical attachment loss ≥ 3 mm), and, when available, a 'healthy' papilla (n = 69; no bleeding-on-probing, probing depth ≤ 4 mm, and clinical attachment loss ≤ 4 mm). Our analyses revealed limited differences between the gingival tissue transcriptional profiles of AgP and CP, with genes related to immune responses, apoptosis, and signal transduction overexpressed in AgP, and genes related to epithelial integrity and metabolism overexpressed in CP. Different classifying algorithms discriminated CP from AgP with an area under the curve ranging from 0.63 to 0.99. The small differences in gene expression and the highly variable classifier performance suggest limited dissimilarities between established AgP and CP lesions. Future analyses may facilitate the development of a novel, 'intrinsic' classification of periodontitis based on molecular profiling.

Genome-wide expression profiling of schizophrenia using a large combined cohort.

Numerous studies have examined gene expression profiles in post-mortem human brain samples from individuals with schizophrenia compared with healthy controls, to gain insight into the molecular mechanisms of the disease. Although some findings have been replicated across studies, there is a general lack of consensus on which genes or pathways are affected. It has been unclear if these differences are due to the underlying cohorts or methodological considerations. Here, we present the most comprehensive analysis to date of expression patterns in the prefrontal cortex of schizophrenic, compared with unaffected controls. Using data from seven independent studies, we assembled a data set of 153 affected and 153 control individuals. Remarkably, we identified expression differences in the brains of schizophrenics that are validated by up to seven laboratories using independent cohorts. Our combined analysis revealed a signature of 39 probes that are upregulated in schizophrenia and 86 that are downregulated. Some of these genes were previously identified in studies that were not included in our analysis, while others are novel to our analysis. In particular, we observe gene expression changes associated with various aspects of neuronal communication and alterations of processes affected as a consequence of changes in synaptic functioning. A gene network analysis predicted previously unidentified functional relationships among the signature genes. Our results provide evidence for a common underlying expression signature in this heterogeneous disorder.