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In the genomic medicine era, the emergence of SARS-CoV-2 was immediately followed by viral genome sequencing and world-wide sequences sharing. Almost in real-time, based on these sequences, resources were developed and applied around the world, such as molecular diagnostic tests, informed public health decisions, and vaccines. Molecular SARS-CoV-2 variant surveillance was a normal approach in this context yet, considering that the viral genome modification occurs commonly in viral replication process, the challenge is to identify the modifications that significantly affect virulence, transmissibility, reduced effectiveness of vaccines and therapeutics or failure of diagnostic tests. However, assessing the importance of the emergence of new mutations and linking them to epidemiological trend, is still a laborious process and faster phenotypic evaluation approaches, in conjunction with genomic data, are required in order to release timely and efficient control measures.

Paraovarian cysts (POCs) develop within the broad ligament of the uterus. POCs are considered to be giant when the threshold of 150 mm is exceeded. Clinical signs and symptoms occur as a consequence of the pressure effect on adjacent organs or due to complications. Abdominal ultrasonography, computed tomography or magnetic resonance imaging are useful imaging tools, but most often the exact origin of such voluminous cysts is revealed only by surgical exploration. The review aims to appraise and update the diagnostic, the histological aspects and the treatment of the giant POCs in rare cases. We carried out a systematic search in Medline-PubMed, Google Scholar and ResearchGate electronic databases. Twenty-seven papers fulfilling the selection criteria were included in the review. The data extracted included information about first author, year of publication, country, patient age, size and side of the POCs, symptoms, tumoral markers, imaging methods, preoperative diagnosis, surgical management and histopathological findings. Although not very numerous, all the studies highlighted the low incidence of giant POCs, the impossibility of establishing the origin of the cystic mass by clinical and imaging methods even with advanced technical tools and the low risk of torsion (11.1%). Despite the recognized benign nature of POCs, we found an unexpected high percent (25.9%) of borderline giant POCs. Surgical excision is the only treatment option. Ovarian-sparing surgery was performed in 85.1% of the cases, and minimally invasive techniques were applied in only 42.9% of the patients, which demonstrates the need of a high-level laparoscopic expertise. Knowledge of this pathology, its recognition as a possible etiology of an abdominopelvic cyst, and a higher awareness of the possibility of a borderline histology in giant POCs are required for the proper management of these particular cases.

An individual's behavior can be defined as a set of complex reactions of the body to internal and external stimuli. Case description: We present a case of a young adult student who, under the circumstances of an anomic environment, causes a female person multiple stab wounds to the cervical region. The patient has an addiction to virtual reality, personal psychiatric history of a depressive disorder, emotional and anxious behavioral disorders, as he was a regular cannabis user. The young man was attending an event where he was consuming alcohol and banned substances (Ecstasy), whose effect combined with antidepressants creates a virtual reality in which the individual has a particular mental state, having the impression that bystanders want to hurt him. Under the impulse of this state, the individual uses a bladed weapon and causes multiple wounds to the victim. The patient is examined in the psychiatric forensic examination commission to determine the discernment at the time of the act of violence and for recommendations regarding safety measures. Conclusion: The approach of hetero-aggression behaviour is based on three categories of causal factors, in a triune concept that implies the consequence of the interaction of the existential environment, with the personality structure of the young individual and with the circumstantial factors that precipitate the act.

Background: Despite significant progress in the diagnosis of contact dermatitis, the identification by specific tests or biomarkers remains an unsolved issue, particularly when needed for the confirmation of the occupational origin of the disease. Objective: To characterize the plasma proteome profile in occupational dermatitis in workers of paint industry. Methods: The study has a case-control design, comparing exposed workers with and without occupational contact dermatitis, matched for age, gender, occupational history, and comorbidities. An immunological assay (Human XL Cytokine Array Kit – ARY022B, R&D Systems) was used to measure the plasma levels of 105 cytokines and chemokines in a pooled sample of the cases and a pooled sample of the controls. Results: A 1.5-fold increase was noticed for interleukin 3, interleukin 10, and leptin in cases, as compared to controls. Fibroblast growth factor-7 and growth/differentiation factor-15 showed a 1.4-fold increase, while interleukin 19, interleukin 31, and macrophage inflammatory protein 3 a had only a 1.3- fold increase. The leukemia inhibitory factor was the only plasma cytokine that showed a 1.3-fold decrease. All other cytokines had a variation of less than 1.2-fold between cases and controls. Conclusion: The recognition of the molecular signatures is very important for an accurate and indisputable diagnosis of occupational contact dermatitis. In workers from the paint industry, plasma levels of interleukins 3, 10, 13 and 19, fibroblast growth factor-7, and growth/differentiation factor-15, together with leukemia inducible factor, may differentiate subjects with contact dermatitis from those without skin lesions.

Diabetes is a chronic metabolic disease due to an absolute or relative deficiency of effective insulin, which primarily causes disruption of carbohydrate metabolism, followed by disruption of lipid, protein, hydromineral and acid-base metabolism, is often a genetically determined disease and/or acquired, with a chronic stage evolution. The importance of the diabetic field in prosthetic rehabilitation is not only determined by the high frequency of complications and the fact that in these patients any aggression, even limited, can lead to a vicious circle in which the local injury aggravates the diabetic condition, and this, in turn, gets the local evolution of the lesions worse, but also by the particularities that the diabetic disease induces at the level of all the elements of the prosthetic field. Chemical diabetes (prediabetes) represents a stage of diabetes, which is characterized by lack of clinical signs and symptoms in diabetes (asymptomatic diabetes). In diabetes, it is characteristic to disturb other forms of metabolism; in diabetes, the entire apparatus for regulating carbohydrate metabolism is affected, the various links of which are closely linked, being controlled by the central nervous system. Material and method: We studied diabetes risk factor in prosthetic rehabilitation on a group of 86 patients with diabetes and obesity. Results and discussions:The anamnesis, the research of the personal and heredocolateral antecedents are compulsory steps that any dentist must go through in the face of more difficult cases. Conclusions: The prophylaxis of this disease is an urgent social necessity nowadays.

COVID-19 risk of infection from someone who does not pose a kind of symptoms is very small; it is possible to get COVID-19 from someone who has a mild cough without feeling sick. The elderly and people with pre-existing medical conditions (high blood pressure, heart disease or diabetes) appear to develop a severe form of the disease, more often than the other categories. By September 7, in Romania, 95,897 cases of people infected with the new coronavirus (COVID-19) were confirmed. 40,454 patients were declared cured and 12,339 asymptomatic patients were discharged 10 days after detection. On September 8, 883 were found of new cases of people infected with SARS-VOC-2. Coronavirus strains are viruses of the class are seven in number, including the 2019-nCoV. Four of the strains cause common colds, while the others have led to epidemics: SARS (Severe Acute Respiratory Syndrome), which erupted in China in 2002 and spread globally in 2003; MERS (Middle East respiratory Syndrome) – was discovered in 2012 in Saudi Arabia; Covid-19 (coronavirus disease that wAS discovered 2019) -, disease triggered by the coronavirus that has was discovered in 2019; new strain of coronavirus was first identified in the city ‘s Wuhan, Hubei Province and China (in December 2019).

Prosthetic deal with methods of morphological-functional and aesthetic restoration of the maxillary (ADM) by means of biocompatible prostheses. The type of restored structures determines the delimitation of two distinct sub-domains: dental prosthetics and maxillofacial prosthetics; the first approaches the restoration of the dento-alveolar arches, and the second the prosthesis of other maxillofacial structures.. Orthodontics as a branch of dentistry has emerged as a way to correct dental malocclusions (poor alignment of teeth), but in contemporary society its goal has become to obtain an optimal position of facial soft tissues, so improving facial aesthetics while obtaining a functional occlusion (bites). Material and method: The paper presents an epidemiological study, conducted by clinical examination and observation sheets, of a representative group of 5 9 children aged 6-16 years, adolescents and young adults, which aimed to analyze the causes associated with the need for application prosthetic treatments in growing patients and establishing the frequency of prosthetic treatment necessary and performed at the level of permanent teeth. Results and discussions: There is a need to establish a prosthetic treatment for the growing patients, highlighting the consequences of non-prosthesis, as well as identifying treatment solutions targeted to each stage of age. Conclusions: Prosthetic treatments present in growing patients, satisfy a small proportion of their needs.

BACKGROUND Gastric cancer (GC) remains an aggressive malignancy with a high rate of mortality, being the third leading cause of cancer-related death. More than one million newly diagnosed cases and 782685 deaths due to GC were reported in 2018. GC is characterized by limited effective treatment options and the lack of consistent biomarkers for the diagnosis and prognosis of these patients. The discovery of new biomarkers useful in the early diagnosis of GC is mandatory. AIM To evaluate the potential of COL10A1 as a circulating biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients. METHODS Plasma and tissue obtained from 49 patients with gastric adenocarcinoma have been used in exploring the expression of COL10A1. Real-time PCR and western blot techniques were used to evaluate COL10A1 level in gastric tumor tissue compared to normal adjacent tissue. The circulating level of COL10A1 was also evaluated by ELISA in plasma of gastric adenocarcinoma patients. Survival analysis was made in order to evaluate the potential of COL10A1 as a biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients. RESULTS Our results showed a significant increase in COL10A1 gene expression and protein levels in gastric tumor tissue compared to adjacent normal tissue (P < 0.05). COL10A1 seems to show an elevated expression from the beginning of carcinogenesis, in the early stages, and its increased level remains elevated during cancer progression. A significant increase of COL10A1 plasma level in gastric adenocarcinoma patients was also identified. Moreover, increased COL10A1 plasma level was associated with poor survival of the patients. Plasma COL10A1 performed a diagnostic value in GC with area under the receiver operating characteristic curve (AUC) of 0.9171 (P = 0.0002), sensitivity of 87.76%, and specificity of 100.0%. Furthermore, this study demonstrated the potential role of plasma COL10A1 in the early detection of GC, as in the early stage, we obtained an AUC of 0.8789 (P = 0.0030), sensitivity of 81.25%, and specificity of 100.0%. CONCLUSION Circulating expression level of COL10A1 is significantly increased in gastric adenocarcinoma patients being associated with poor survival and is a potential biomarker for early detection of GC.

The role of cancer stem cells in gastrointestinal cancer-associated death has been widely recognized. Gastrointestinal cancer stem cells (GCSCs) are considered to be responsible for tumor initiation, growth, resistance to cytotoxic therapies, recurrence and metastasis due to their unique properties. These properties make the current therapeutic trials against GCSCs ineffective. Moreover, recent studies have shown that targeting stem cell surface markers or stemness associated pathways might have an additional off-target effect on the immune system. Recent advances in oncology and precision medicine have opened alternative therapeutic strategies in the form of cancer immunotherapy. This approach differs from classical anti-cancer therapy through its mechanism of action involving the activation and use of a functional immune system against tumor cells, instead of aiming physically destruction of cancer cells through radio- or chemotherapy. New immunological approaches for GCSCs targeting involve the use of different immune cells and various immune mechanisms like targeting specific surface antigens, using innate immune cells like the natural killer and T cells, T-cell chimeric antigen receptor technology, dendritic cell vaccine, or immune checkpoint inhibitors. In this respect, better understandings of immune regulatory mechanisms that govern anti-tumor response bring new hope in obtaining long-term remission for cancer therapy.

Ovarian cystic lesions, once considered uncommon in children, represent nowadays subject for many studies. Controversies regarding the diagnostic and treatment still exist. Unspecific symptoms and difficulties in performing an accurate ultrasound in children, sometimes led to misdiagnose this condition. Ovarian cystic lesions in premenarcheal girls may have hormonal influence, changing the biochemical balance, so an endocrinologist should be consulted. The main goal is to preserve the adnexal tissue. The purpose of this study is to analize the diagnostic and treatment of ovarian cystic lesions in premenarcheal girls, highlighting the opportunity of a multidisciplinary team and the necessity of the ovarian preservation.

Oral anticoagulants have been used for more than 50 years as antithrombotic agents, particularly in the primary and secondary prophylaxis of thromboembolic disorders. Our study�s purpose is to synthetize and analyze the toxicological methods used to determine the oral anticoagulants, described in the literature, so we can identify the optimal methods, taking into consideration the diversity of forensic medicine workload. In the electronic databases, for the period 1990-2019, there were identified 56 articles that included the searched keywords. Of these, 28 were included in our study. We excluded the articles that were not lining up with the objective of our study, the update-type articles and the case studies. After analyzing the literature, it was observed that liquid chromatography-mass spectrometry is the ideal method for detecting low-dosed drugs, such as oral anticoagulants.

The possible use of biochemical markers in the postmortem diagnosis of sudden cardiac deaths is well known in the forensic setting, though several issues have limited its widespread adoption. The aim of the present study was to describe the discovery of cardiac troponin I (cTnI), myoglobin (MYO) and creatinine kinase MB (CK-MB) in femoral whole blood (FWB), pericardial fluid (PF) and vitreous humor (VH) samples, that were collected post-mortem, in various cases of death related to ischemic heart disease, using the rapid diagnostic test 'Cardiac Markers Combo Rapid Test Device'. The authors conducted a prospective study in which they analyzed a total of 100 autopsies performed at the Legal Medicine Clinical Service of Galați County. The results of the present study showed that cardiac markers can be determined using rapid diagnostic tests for blood from the femoral vein and pericardial fluid, but not for the vitreous humor. Using postmortem biochemical markers of myocardial ischaemia requires caution and flexibility, so that the forensic pathologist has to take into consideration, when interpreting the results, both the postmortem interval, and the type of biological sample. Keywords: sudden death, cardiac, markers, troponin, forensic pathology

This article describes rehabilitation of one case, complex psychiatric treatment, facial asimetry, with mandibular and maxilla missing teeth and dental disharmony, with a fixed and also removable hybrid prosthesis.Rehabilitation with fixed or removable prosthesis is even more challenging when the edentulous span is long and the ridge is irregular deformities and unfavorable biomechanics encountered at the prosthetic field for complex rehabilitation. In such situation, a fixed-removable prosthesis allows favorable biomechanical stress distribution along with restoration of esthetics, phonetics, comfort, hygiene, and better postoperative care and maintenance.

Endometrial stromal sarcoma (ESS) is a rare tumor, predominantly occurring as a primary tumor of the uterus. Rare cases of primary extrauterine ESS (EESS) have been reported. Low-grade ESS (LG-ESS) is more common than high-grade ESS (HG-ESS). We present five cases of ESS and one case of EESS. All cases received external radiotherapy (EBRT) at the Radiotherapy Department of the Emergency Clinical Hospital ‘Sfantul Apostol Andrei’ Galati, during 2004-2020. Five cases underwent EBRT in two-dimensional (2D) technique and only one patient received EBRT with three-dimensinal conformational radiotherapy (3DCRT) technique with a linear accelerator, Elekta Synergy. Five patients were referred to postoperative radiotherapy after hysterectomy. The median age of the patients was 57.4 years. One patient was referred to radiotherapy with palliative intent. EESS localized in the retroperitoneum, in the para-aortic region, was identified in one 64-year-old patient with a personal history of hysterectomy and bilateral salpingo-oophorectomy in 1997; EESS was complicated with vertebral extension at the L1-L2 level and spinal cord compression syndrome. ESS represents a rare diagnosis and a high- or low-grade tumor profile is distinguished by immunohistochemistry (IHC) tests. Up to 30% of patients have EESS at presentation. The treatment of ESS is multimodal, its management requiring a multidisciplinary team, and it is different according to the primary tumor location and tumor staging. The role of adjuvant radiotherapy remains controversial in high-grade EESS and due to the rarity of these cases there are limited data concerning the efficacy of adjuvant EBRT available from prospective randomized control clinical trials.

Background Mortality is often used as an indicator of public health efforts. Even if mortality in psychiatric hospitals decreased since the introduction of modern treatment, the death toll is still high. The authors have analyzed the forensic autopsy data and the medical documentation regarding 115 death cases from psychiatric hospitals in south-eastern Romania during the period of 2000–2020. Results The average annual mortality rate was 5.13‰, the necropsy data corroborated with those from the medical documentary material indicates acute myocardial infarction as the dominant cause, with 65 (56.5%) cases, followed by upper respiratory tract occlusion with 23 cases (20%) and pulmonary thromboembolism in 4 cases (12.2%). Furthermore, in 6 cases (5.2%) the cause of death was traumatic: 4 cases of cranio-cerebral trauma and 2 cases of hanging. Conclusions In the mortality structure of psychiatric patients, cardiac death predominated, being influenced by the cardiotoxic effect of medication administered for the specific pathology; hence, an early involvement of cardiologists in the follow-up of patients and the finding of treatment schemes with a reduced cardiotoxic effect are required.

The pathophysiological involvement of uric acid in cardiovascular disease has been intensively addressed in the last decades by the medical community. The tendencies to elucidate its role in cardiac events have been carried out in numerous researches with controversial results. In an attempt to understand this phenomenon, the existence of a paradox is admited, according to which uric acid behaves as an antioxidant, capturing reactive oxygen species, and in the context of an existing cardiac pathology, manifests a precipitating oxidative effect of circulating lipids, there being also present. inflammatory substrate. The involvement of the target organs in hypertension, along with other factors such as hyperlipidemia, obesity, pathologies of the valvular apparatus, contributes to the appearance of hyperuricemia of excretory cause. The ability of xanthine oxidoreductase to produce reactive oxygen species that contribute to the occurrence of oxidative stress and endothelial dysfunction has redirected our visions to a more complex approach to ischemic heart disease. And the use of xanthine oxidoreductase inhibitors in cardiovascular disease in patients with hyperuricemia has allowed to appreciate real benefits in improving renal function and preventing atherosclerosis. Keywords: uric acid, cardiovascular disease, factor

Drug facilitated sexual assault (DFSA) can be defined as sexual activity occurring where consent is invalid or absent due to the effects of drugs and/or alcohol. We report a rare case of pro-active drug facilitated sexual assault involving non-oral administration of sedative-hypnotic intoxicant without primary alcoholic ingestion. For eight years, a male nurse administered sedative-hypnotic drugs to patients admitted to the hospital unit, in order to subsequently maintain sexual intercourse with them. The intravenous administration without primary alcoholic ingestion distinguishes this case of pro-active drug facilitated sexual assault from those presented in associated literature.

Drug facilitated sexual assault (DFSA) can be defined as sexual activity occurring where consent is invalid or absent due to the effects of drugs and/or alcohol. We report a rare case of pro-active drug facilitated sexual assault involving non-oral administration of sedative-hypnotic intoxicant without primary alcoholic ingestion. For eight years, a male nurse administered sedative-hypnotic drugs to patients admitted to the hospital unit, in order to subsequently maintain sexual intercourse with them. The intravenous administration without primary alcoholic ingestion distinguishes this case of pro-active drug facilitated sexual assault from those presented in associated literature. Keywords: Drug facilitated sexual assault; Benzodiazepines; Barbiturates

Primary malignant melanoma of the small bowel is extremely rare. A limited number of cases was described in the specialty literature. The small bowel is most frequently affected by metastatic tumors of other primary lesions, especially epidermal. We report the case of a 77 years old male patient with primary bowel malignant melanoma, diagnosed histologically and immunohistochemically after segmental ileal resection. It was not discovered a primary lesion atskin, eye, anus and rectum levelor with other localization, through the investigations performed after surgery.

Gastric cancer (GC) remains an important cause of cancer death worldwide with a high mortality rate due to the fact that the majority of GC cases are diagnosed at an advanced stage when the prognosis is poor and the treatment options are limited. Unfortunately, the existing circulating biomarkers for GC diagnosis and prognosis display low sensitivity and specificity and the GC diagnosis is based only on the invasive procedures such as upper digestive endoscopy. There is a huge need for less invasive or non-invasive tests but also highly specific biomarkers in case of GC. Body fluids such as peripheral blood, urine or saliva, stomach wash/gastric juice could be a source of specific biomarkers, providing important data for screening and diagnosis in GC. This review summarized the recently discovered circulating molecules such as microRNAs, long non-coding RNAs, circular RNAs, which hold the promise to develop new strategies for early diagnosis of GC.

Cutaneous metastases from endometrial cancer are rare and unusual. This is the case of a 72 years old female patient, diagnosed in 2018 with G3 endometrial serous carcinoma (ESC). At 18 months from the surgical intervention, the patient developed bilateral inguinal lymph nodes metastases and skin secondary lesions; histological and immunohistochemical tests were performed. Computed tomography scan did not indicate visceral secondary lesions, local or regional relapses. We present the treatment practiced, the case's evolution and we discuss about epidemiology, molecular biology, treatment options and management of advanced and local lesions. The appearance of skin metastases in theses cases is associated with poor prognosis and treatment options are limited to palliative chemotherapy and radiotherapy.

Background Although there is evidence of genetic correlation between bipolar disorder (BP) and ADHD, the extent of the shared genetic risk and whether childhood ADHD (cADHD) influences the characteristics of the adult BP remain unclear. Our objectives were: (i) to test the ability of polygenic risk scores (PRS) derived from the latest PGC ADHD-GWAS (Demontis et al., 2019) to predict the presence of cADHD in BP patients; (ii) to examine the hypothesis that BP preceded by cADHD is a BP subtype with particular clinical traits and (iii) partially shares its molecular basis with ADHD. Method PRS derived from the ADHD-GWAS-2019 were tested in BP patients (N = 942) assessed for cADHD with the Wender Utah Rating Scale and in controls from Romania and UK (N = 1616). Results The ADHD-PRS differentiated BP cases with cADHD from controls. Proband sex and BP age-of-onset significantly influenced the discriminative power of the ADHD-PRS. The ADHD-PRS predicted the cADHD score only in males and in BP cases with early age-of-onset (≤21 years). Bipolar patients with cADHD had a younger age-of-onset of mania/depression than patients without cADHD. The ADHD-PRS predicted the BP-affection status in the comparison of early-onset BP cases with controls suggesting a partial molecular overlap between early-onset BP and ADHD. Limitations Retrospective diagnosis of cADHD, small sample size. Conclusions The PRS-analysis indicated an acceptable predictive ability of the ADHD-SNP-set 2019 in independent BP samples. The best prediction of both cADHD and BP-affection status was found in the early-onset BP cases. The results may have impact on the individual disease monitoring.

Over recent years stem cells have stood out as a promising tool for regenerative medicine, providing alternative therapeutic solutions for a large number of diseases. Many clinical trials using stem cells or induced pluripotent stem cells are focused on the repair and regeneration of various tissues and organs in degenerative diseases, whose current treatment only succeeds in slowing down the progression of the disease. Although the preliminary results are interesting, further studies are required in order to evaluate the safety and benefits of stem cell therapy, considering the teratoma development and ethical considerations in embryonic stem cell cases or reprogramming-induced somatic mutations and epigenetic defects. This review summarizes several current clinical and nonclinical data on the use of embryonic stem cells, mesenchymal stem cells, and induced pluripotent stem cells in various diseases.

The article explores the challenges of ensuring voluntary and informed consent which is obtained from potential research subjects in the north-eastern part of Romania. This study is one of the first empirical papers of this nature in Romania. The study used a quantitative survey design using the adapted Quality of Informed Consent (QuIC) questionnaire. The target population consisted of 100 adult persons who voluntarily enrolled in clinical trials. The informed consent form must contain details regarding the potential risks and benefits, the aim of the clinical trial, study design, confidentiality, insurance and contact details in case of additional questions. Our study confirmed that although all required information was included in the ICF, few clinical trial participants truly understood it. We also found that the most important predictive factor for a good subjective and objective understanding of the clinical trial was the level of education. Our study suggests that researchers should consider putting more effort in order to help clinical trials participants achieve a better understanding of the informed consent. In this way they will ensure that participants' decision-making is meaningful and that their interests are protected.

High grade gliomas represent one of the most aggressive and treatment-resistant types of human cancer, with only 1-2 years median survival rate for patients with grade IV glioma. The treatment of glioblastoma is a considerable therapeutic challenge; combination therapy targeting multiple pathways is becoming a fast growing area of research. This review offers an up-to-date perspective of the literature about current molecular therapy targets in high grade glioma, that include angiogenic signals, tyrosine kinase receptors, nodal signaling proteins and cancer stem cells related approaches. Simultaneous identification of proteomic signatures could provide biomarker panels for diagnostic and personalized treatment of different subsets of glioblastoma. Personalized medicine is starting to gain importance in clinical care, al- ready having recorded a series of successes in several types of cancer; nonetheless, in brain tumors it is still at an early stage.

The G72/G30 gene is one of the common loci shared both by schizophrenia and bipolar disorder. Studies accumulating since the discovery of this gene complex produced controversial results in both disorders in different populations. Objective We investigated the association between the G72/G30 gene and bipolar I disorder (BPI) in the Romanian population paying special attention to the association of G72/G30 with lifetime psychosis and in particular with persecutory delusions in BPI patients. Method Fourteen G72/G30-SNPs were genotyped in a Romanian sample of 198 BPI patients and 180 controls screened for psychiatric disorders. Statistical analysis was performed with FAMHAP and HAPLOVIEW-v3.32. The significance level of the results was corrected through permutations in 100,000 simulations. Results None of the fourteen SNPs was associated with the global diagnosis of BPI in our total patient sample or with the psychotic BPI subtype. When confining the psychotic phenotype to persecutory delusions, we observed trends to association for SNPs previously associated with schizophrenia and persecutory delusions in BPI [M21 (P = 0.080); M22 (P = 0.092; P = 0.042 under dominant transmission model); M24 (P = 0.092)]. Four SNPs reached nominal significance in the non-psychotic BPI subgroup [rs3916965 (M12) (P = 0.044), rs1935057 (P = 0.037), rs3916967 (M14) (P = 0.043), and rs2391191 (M15, non-synonymous) (P = 0.043)]. After correction through permutations, the haploblock GA including M14 and M15 showed a trend to association with BPI (P = 0.0524; OR = 1.82) in the non-psychotic BPI subgroup. Conclusion We report a potential association of different G72/G30-SNPs with non-psychotic mood episodes and with persecutory delusions in BPI Romanian patients. The results represent a first partial replication of two studies: Williams et al. (2006) and Schulze et al. (2005). The results have just a suggestive value since the Bonferroni correction for multiple testing was not applied.

Caenorhabditis elegans is particularly suitable for obtaining quantitative data about behavior, neuronal activity, gene expression, ecological interactions, quantitative traits, and much more. To exploit the full potential of these data one seeks to interpret them within quantitative models. Using two examples from the C. elegans literature we briefly explore several types of modeling approaches relevant to worm biology, and show how they might be used to interpret data, formulate testable hypotheses, and suggest new experiments. We emphasize that the choice of modeling approach is strongly dependent on the questions of interest and the type of available knowledge.

We investigated the influence of the age-of-onset (AO) on the association of 45 loci conferring risk for bipolar disorder (BP) and schizophrenia with BP-type-I in a Romanian sample (461 patients, 436 controls). The AO-analysis implicated the EGFR gene, as well as loci in other genes, in the AO variation of BP-type-I and revealed for the first time the link between BP-type-I and risk variants considered specific to schizophrenia (polymorphisms in MMP16/RIPK2 and CNNM2 genes).

ABSTRACT An important goal of oncology is the development of cancer risk-identifier biomarkers that aid early detection and target therapy. High-throughput profiling represents a major concern for cancer research, including brain tumors. A promising approach for efficacious monitoring of disease progression and therapy could be circulating biomarker panels using molecular proteomic patterns. Tailoring treatment by targeting specific protein–protein interactions and signaling networks, microRNA and cancer stem cell signaling in accordance with tumor phenotype or patient clustering based on biomarker panels represents the future of personalized medicine for brain tumors. Gathering current data regarding biomarker candidates, we address the major challenges surrounding the biomarker field of this devastating tumor type, exploring potential perspectives for the development of more effective predictive biomarker panels.

Pancreatic cancer is one of the most aggressive and lethal malignancies. Despite remarkable progress in understanding pancreatic carcinogenesis at the molecular level, as well as progress in new therapeutic approaches, pancreatic cancer remains a disease with a dismal prognosis. Among the mechanisms responsible for drug resistance, the most relevant are changes in individual genes or signaling pathways and the presence of highly resistant cancer stem cells (CSCs). In pancreatic cancer, CSCs represent 0.2%-0.8% of pancreatic cancer cells and are considered to be responsible for tumor growth, invasion, metastasis and recurrence. CSCs have been extensively studied as of late to identify specific surface markers to ensure reliable sorting and for signaling pathways identified to play a pivotal role in CSC self-renewal. Involvement of CSCs in pancreatic cancer pathogenesis has also highlighted these cells as the preferential targets for therapy. The present review is an update of the results in two main fields of research in pancreatic cancer, pathogenesis and therapy, focused on the narrow perspective of CSCs.

Two recent studies reported evidence for association between genetic variation of the positional candidate gene P2RX7 on chromosome 12q24 and bipolar I disorder (BPI) [Barden et al. (2006); Am J Med Genet Part B 141B:374-382; McQuillin et al. (2008); Mol Psychiatry 13:1-7] and one study found association with unipolar major depression (Mdd-UP) [Lucae et al. (2006); Hum Mol Genet 15:2438-2445]. In the present work, we aimed to replicate the SNP that showed the strongest association in the above-mentioned studies, namely rs2230912 (P2RX7-E13A) resulting in a change of the amino acid glutamine to arginine at position 460 (Gln460Arg), in four European bipolar I disorder samples from Germany, Poland, Romania, and Russia totaling 1,445 patients, in a German sample of recurrent Mdd-UP patients (N = 640), and a control sample of 2,006 subjects. We found no allelic or genotypic association between rs2230912 and BPI or Mdd-UP both in the national samples and in the combined European patient sample. Additional studies are needed to clarify the potential involvement of P2RX7 and of SNP rs2230912 in the etiology of major affective disorders.

BackgroundThe G72/G30 gene is one of the common loci shared both by schizophrenia and bipolar disorder. Studies accumulating since the discovery of this gene complex in 2002 produced controversial results in both disorders in different populations.ObjectiveWe investigated the association between G72/G30 gene and bipolar I disorder (BPI) in the Romanian population paying special attention to the association of G72/G30 locus with lifetime psychosis in BPI patients.MethodFourteen G72-SNPs were genotyped in a Romanian sample of 198 BPI patients and 180 controls screened for psychiatric disorders in the Institute of Human Genetics, Life & Brain Center of the University of Bonn, Germany. Statistical analysis was performed with FAMHAP and Haploview-v3.32. The significance level of the results was corrected for multiple testing through permutations in 100,000 Monte Carlo simulations.ResultsNone of the fourteen SNPs was associated with the global diagnosis of BPI in our total patient sample or with the psychotic BPI subtype. But four SNPs reached nominal significance in the non-psychotic BPI subgroup [rs3916965 (M12) (P=0.044), rs1935057 (P=0.037), rs3916967 (M14) (P=0.043), rs2391191 (M15, non-synonymous) (P=0.043)]. In the non-psychotic subgroup, the haploblock including M14 and M15 (GA) remained significantly associated with BPI after correction through permutations (P=0.0524; OR=1.82).ConclusionOur results are the first replication of the study by Williams et al. (2006) reporting the same G72-SNPs [M12(A) and the functional SNP M15(A)], with the same alleles, to be associated with non-psychotic BPI disorder.