Recent Advances In Molecular Diagnosis Research Articles

The Recent Advances in Molecular Diagnosis of Soft Tissue Tumors

Soft tissue tumors are rare mesenchymal tumors with divergent differentiation. The diagnosis of soft tissue tumors is challenging for pathologists owing to the diversity of tumor types and histological overlap among the tumor entities. Present-day understanding of the molecular pathogenesis of soft tissue tumors has rapidly increased with the development of molecular genetic techniques (e.g., next-generation sequencing). Additionally, immunohistochemical markers that serve as surrogate markers for recurrent translocations in soft tissue tumors have been developed. This review aims to provide an update on recently described molecular findings and relevant novel immunohistochemical markers in selected soft tissue tumors.

Recent Advances in Molecular Diagnosis of Pulmonary Fibrosis for Precision Medicine.

Pulmonary fibrosis is a serious, progressive lung disease characterized by scarring and stiffening lung tissues, affecting the respiratory system and leading to organ failure. It is a complex disease consisting of alveolar damage, chronic inflammation, and a varying degree of lung fibrosis. Significant challenges with pulmonary fibrosis include the lack of effective means to diagnose the disease at early stages, identify patients at higher risks of progress, and assess disease progression and treatment response. Precision medicine powered by accurate molecular profiling and phenotyping could significantly improve our understanding of the disease's heterogeneity, potential biomarkers for diagnosis and prognosis, and molecular targets for treatment development. This Review discusses various translational model systems, including organoids and lung-on-a-chip systems, biomarkers in single cells and extracellular vesicles, and functional pharmacodynamic markers. We also highlight emerging sensing technologies for molecular characterization of pulmonary fibrosis and biomarker detection.

Muscle Biopsy: A Requirement for Precision Medicine in Adult-Onset Myopathy.

Muscle biopsy is a fundamental procedure to assist the final diagnosis of myopathy. With the recent advances in molecular diagnosis, serology tests, and mechanism-based classification in myopathy, the précised diagnosis for myopathy required the applications of multiple tools. This study intends to reappraise the benefit of muscle biopsy in adult-onset myopathy under the setting of an optimized muscle biopsy protocol and comprehensive serology tests. A one-group pretest-posttest study design was used. The pre- and post-biopsy diagnoses and treatments in 69 adult patients were compared. Muscle biopsy yielded 85.5% of definitive diagnoses, including changes in pre-biopsy diagnoses (40.6%) and narrowing down the suspicious myopathies (49.3%). The demographic data and clinical parameters between the group “with change” and “without change” after biopsy were not different. Among those with changes in diagnosis, 39.3% also had a corresponding shift in treatment, which benefits the patients significantly. Regarding the most common adult-onset myopathy, idiopathic inflammatory myopathy (IIM), 41% of patients with pre-biopsy diagnosis as IIM had changes in their IIM subtype diagnosis, and 53% was finally not IIM after muscle biopsy. Although there have been advances in molecular diagnosis recently, muscle biopsy still undoubtedly critically guided the diagnosis and treatment of adult-onset myopathy in the era of precision medicine.

Global scenario and recent advances in molecular diagnosis and management of drug-resistant tuberculosis

Tuberculosis (TB) is one of the oldest communicable bacterial diseases, spreads predominantly by inhalation of infected respiratory droplets. It is a curable and preventable disease yet remains the leading infectious cause of human death worldwide. The TB burden is high among developing nations of Asia and Africa. Major obstacles in controlling TB are patient’s non-compliance to the anti-tubercular therapy, co-infection with Human immunodeficiency virus (HIV), low socioeconomic status, crowded living condition, inadequate rapid diagnostic testing facilities especially in resource-poor developing countries, delay in diagnosis and initiation of therapy, and the emergence of drug-resistant strains of Mycobacterium tuberculosis (MTB).  Multidrug-resistant (MDR-TB), extensively drug-resistant (XDR-TB), and total drug-resistant (TDR-TB) MTB strains are difficult to treat and are associated with frequent treatment failures and high mortality. The recent advent of molecular techniques including nucleic acid amplification tests (NAATs) and whole-genome sequencing (WGS) have significantly ameliorated the rapid detection of TB cases and drug-resistant MTB. This, in turn, enabled the early initiation of therapy and development of novel treatment plans which is crucial for the global TB elimination target. The World Health Organization (WHO) 2020 guideline prioritizes the use of newer drugs as part of all-oral regimens for the treatment of MDR-TB. Apart from the use of newer drug delivery methods, host factors including immune functions and cytokine responses as well as mycobacterial enzymatic pathways are targeted in TB drug development. Adjuvant therapy employing host-directed approaches is increasingly studied through the time-tested pathogen-targeted approach remains the mainstay in the current treatment of MDR-TB.

Stargardt disease: Multimodal imaging: A review.

Stargardt disease (STGD1) is an autosomal recessive retinal dystrophy, characterised by bilateral progressive central vision loss and subretinal deposition of lipofuscin‐like substances. Recent advances in molecular diagnosis and therapeutic options are complemented by the increasing recognition of new multimodal imaging biomarkers that may predict genotype and disease progression. Unique non‐invasive imaging features of STDG1 are useful for gene variant interpretation and may even provide insight into the underlying molecular pathophysiology. In addition, pathognomonic imaging features of STGD1 have been used to train neural networks to improve time efficiency in lesion segmentation and disease progression measurements. This review will discuss the role of key imaging modalities, correlate imaging signs across varied STGD1 presentations and illustrate the use of multimodal imaging as an outcome measure in determining the efficacy of emerging STGD1 specific therapies.

BK Polyomavirus Nephropathy in Kidney Transplantation: Balancing Rejection and Infection.

BK polyomavirus nephropathy (BKVN) and allograft rejection are two closely-associated diseases on opposite ends of the immune scale in kidney transplant recipients. The principle of balancing the immune system remains the mainstay of therapeutic strategy. While patient outcomes can be improved through screening, risk factors identification, and rapid reduction of immunosuppressants, a lack of standard curative therapy is the primary concern during clinical practice. Additionally, difficulty in pathological differential diagnosis and clinicopathology’s dissociation pose problems for a definite diagnosis. This article discusses the delicate evaluation needed to optimize immunosuppression and reviews recent advances in molecular diagnosis and immunological therapy for BKVN patients. New biomarkers for BKVN diagnosis are under development. For example, measurement of virus-specific T cell level may play a role in steering immunosuppressants. The development of cellular therapy may provide prevention, even a cure, for BKVN, a complex post-transplant complication.

Recent Advances in Molecular diagnosis curbing the COVID-19

WHO assigned name SARS-CoV-2 to virus causing Corona Virus Disease (COVID-19)whichemerged in Wuhan city of Hubei province. It causes acute febrile illness with respiratory distress syndrome (ARDS). In 21 st century SARS-CoV-2 emerged as highly pathogenic corona virus for humans after SARS and MERS. World health organization declaredCOVID-19 outbreak a public health emergency of international concern on 30 of January 2020 (WHO, 2020; Tang et al., 2020; Wu and McGoogan, 2020).The genome of coronavirus and its phylogenetic analysis indicate that it placed in distinct clad from other human β corona virus which caused SARS and MERS.

Recent Advances in Molecular Diagnosis and Prognosis of Childhood B Cell Lineage Acute Lymphoblastic Leukemia (B-ALL).

B cell lineage acute lymphoblastic leukemia is the most common leukemia occurring in children and young adults and is the leading cause of cancer related deaths. The 5year overall survival outcome in children with B-ALL has improved significantly in the last few decades. In the past, the discovery of various genetic alterations and targeted therapy have played a major role in decreasing disease-related deaths. In addition, numerous advances in the pathogenesis of B-ALL have been found which have provided better understanding of the genes involved in disease biology with respect to diagnostic and prognostic implications. Present review will summarize current understanding of risk stratification, genetic factors including cytogenetics in diagnosis and prognosis of B-ALL.

Molecular phenotyping of rejection-related changes in mucosal biopsies from lung transplants.

Diagnosing lung transplant rejection currently depends on histologic assessment of transbronchial biopsies (TBB) with limited reproducibility and considerable risk of complications. Mucosal biopsies are safer but not histologically interpretable. Microarray-based diagnostic systems for TBBs and other transplants suggest such systems could assess mucosal biopsies as well. We studied 243 mucosal biopsies from the third bronchial bifurcation (3BMBs) collected from seven centers and classified them using unsupervised machine learning algorithms. Using the expression of a set of rejection-associated transcripts annotated in kidneys and validated in hearts and lung transplant TBBs, the algorithms identified and scored major rejection and injury-related phenotypes in 3BMBs without need for labeled training data. No rejection or injury, rejection, late inflammation, and recent injury phenotypes were thus scored in new 3BMBs. The rejection phenotype correlated with IFNG-inducible transcripts, the hallmarks of rejection. Progressive atrophy-related changes reflected by the late inflammation phenotype in 3BMBs suggest widespread time-dependent airway deterioration, which was especially pronounced after two years posttransplant. Thus molecular assessment of 3BMBs can detect rejection in a previously unusable biopsy format with potential utility in patients with severe lung dysfunction where TBB is not possible and provide unique insights into airway deterioration. ClinicalTrials.gov NCT02812290.

2787. Respiratory Syncytial Virus in Elderly Adults

BackgroundThe role of respiratory viruses other than influenza in acute respiratory tract infections (ARTI) among elderly adults has probably been underestimated. Recent advances in molecular diagnosis have made the rapid identification of RSV infection possible.The aim of our study was to assess the role of RSV in patients older than 65 years.MethodsProspective observational study (April 2018–February 2019) conducted in a 137-bed institution in Buenos Aires, Argentina. All consecutive elderly patients (>65 years) admitted with ARTI were included. Clinical and laboratory parameters as well as nasopharyngeal swab for respiratory viruses were obtained. Blood cultures and sputum collection, were analyzed. Viral detection was performed according to CDC real-time RT–PCR assay. All patients underwent clinical follow-up during hospitalization and up to 30 days after discharge.ResultsA total of 124 patients were recruited (mean age 82 years; range: 65–98) 58% female. Clinical diagnosis at admission were: community-acquired pneumonia 90 (72%), COPD exacerbation 11 (9%), acute bronchitis 10 (8%), healthcare-associated pneumonia 8 (7%) influenza like síndrome 5 (4%). Blood cultures were obtained in 92 patients: 4 positives for Streptococcus pneumoniae, 3 E. coli, 2 SAMS, 1 Klebsiella pneumoniae. Sputum was obtained in 20 patients, none were positive.The viral results of the124 samples were: RSV 13 (10.4%), Influenza B 9 (7.2%), Influenza A 8 (6.4%).Regarding RSV positive patients, the mean age was 87 years and 69% were female. 30 % had history of heart failure and 30 % had history of COPD. Clinical diagnosis on admission were: CAP 10 (77%), COPD exacerbation 2 (15%) and bronchitis 1 (8%). Non productive cough was present in 46% and bronchospasm in 85%. Mean time of hospitalization was 9 days (R: 4–16) and fever duration 1 day (R: 0–2). The median duration of antibiotic treatment was 9.5 days (R: 4 to 15) No viral nor bacterial coinfections were observed. No early mortality was registered, global mortality was 23% (3 patients). Death was clinically related to RSV infection.ConclusionThis study suggest that RSV is a relevant respiratory pathogen in the elderly population, with significant associated morbidity and mortality rates. Current treatment is limited to supportive care and prevention to standard infection control practices. A new approach is needed to improve RSV infection management.Disclosures All authors: No reported disclosures.

Rol del virus sincicial respiratorio en una cohorte de adultos mayores

El rol de los virus respiratorios distintos de influenza en las infecciones respiratorias agudas en los adultos mayores ha sido probablemente subestimado. En los últimos años, los avances en técnicas moleculares de diagnóstico han hecho posible la identificación rápida del virus sincicial respiratorio humano (HRSV).Realizamos un estudio prospectivo observacional para evaluar el rol del HRSV en mayores de 65 años que se hospitalizaron por infecciones respiratorias en nuestra institución, ubicada en la ciudad de La Plata, provincia de Buenos Aires. Fueron reclutados 124 pacientes y el HRSV se detectó en 13, influenza B en 9 e influenza A en 8. La presentación clínica más frecuente de los pacientes con HRSV fue el broncoespasmo y afectó principalmente a personas con comorbilidades. HRSV fue responsable de un número importante de internaciones por enfermedad respiratoria aguda en mayores de 65 años en nuestra institución y se asoció a mortalidad elevada (23%).

Recent Advances in Molecular Diagnosis of Pseudomonasaeruginosa Infection by State-of-the-Art Genotyping Techniques.

Pseudomonas aeruginosa is a rod-shaped Gram-negative bacterium which is notably known as a pathogen in humans, animals, and plants. Infections caused by P. aeruginosa especially in hospitalized patients are often life-threatening and rapidly increasing worldwide throughout the years. Recently, multidrug-resistant P. aeruginosa has taken a toll on humans’ health due to the inefficiency of antimicrobial agents. Therefore, the rapid and advanced diagnostic techniques to accurately detect this bacterium particularly in clinical samples are indeed necessary to ensure timely and effective treatments and to prevent outbreaks. This review aims to discuss most recent of state-of-the-art molecular diagnostic techniques enabling fast and accurate detection and identification of P. aeruginosa based on well-developed genotyping techniques, e.g., polymerase chain reaction, pulse-field gel electrophoresis, and next generation sequencing. The advantages and limitations of each of the methods are also reviewed.

Bacteriological profile and antibiogram of neonatal septicemia in a tertiary care hospital

Background: Neonatal sepsis is a clinical syndrome which is characterised by signs and symptoms of infection which may or may not be accompanied by bacteraemia within the first month of life. The bacteriological profile of neonatal sepsis is under constant change with the advances in the diagnosis and treatment. Blood culture is still the mainstay of investigation of potential sepsis in spite of the recent advances in molecular diagnosis of fungal and bacterial sepsis. Most common bacterial organisms responsible for neonatal septicaemia in developing countries like Bangladesh, India, Nigeria, Pakistan, are Klebsiella, Escherichia coli, Enterobacter etc. The present study was undertaken to describe the spectrum of the isolates in cases of neonatal septicaemia, and their antimicrobial susceptibility pattern. The study was carried out over a one year period. Method: A total of 357 suspected patients of neonatal septicaemia were included in the study. Blood samples were collected with aseptic precautions preferably prior to the initiation of empiric antibiotic therapy. The bottles were incubated aerobically at 370 C for 7 days and subcultured on blood agar and Mac Conkey agar. If growth appeared the isolates were processed as per standard microbiological techniques and the isolates were identified. Antibiotic sensitivity testing was performed on Mueller?Hinton agar plates by modified Kirby?Bauer disk diffusion method as per Clinical Laboratory Standard Institute guidelines. Results: Of the 357 samples studied, growth was observed in 154 samples. Gram positive organisms constituted 37.66% and gram negative bacilli constituted 62.34% of the isolates. The predominant pathogens isolated were Klebsiella species, Coagulase Negative Staphylococci, Staphylococcus aureus followed by Non fermenting gram negative bacilli. 71.43% of the Staphylococcus aureus isolates were found to be methicillin resistant.96.05% of the Enterobacteriaceae were found to be Extended Spectrum Beta Lact

Clinical relevance of KRAS mutations in codon 13: Where are we?

Recent advances in molecular diagnosis and the trend towards personalized medicine have made colorectal cancer one of the tumors where therapies have significantly improved patient survival after metastasis development. KRAS mutations in codon 12 and 13 are recognized biomarkers that are analyzed in clinic previously for anti-EGFR therapies administration. Since originally mutations in both codons were considered as a predictor of lack of response to cetuximab or panitumumab, the European Medicines Agency and the US Food and Drug Administration suggested that patients harboring any of those mutations should be excluded from the treatment. However, subsequent retrospective analysis has shown that mutations in codon 12 and codon 13 of KRAS gene could be different in their biological characteristics and as a result could confer variable effects in patients. In addition and increasing and sometimes contradictory number of solutions have been published demonstrating that patients with mutations in codon 13 could have worse outcome but could obtain a significant clinical benefit from anti-EGFR therapies. Here, we review and update the latest data on the biological role leading to a predictive outcome and benefit from anti-EGFR antibodies in patients with specific KRAS mutations in codon 13.

Non‐small cell lung cancer: One size doesn't fit all

Management of lung cancer in the past was based on clinical parameters that included disease stage and histology. Patients who did not have small cell lung cancer were labeled collectively as having non-small cell lung cancer (NSCLC) and all treated with the same chemotherapy, since clinical trials had shown no differential effect of chemotherapy on outcomes for the various histological subtypes. As a result of this broad approach the median survival of patients with advanced stage disease was limited to 10 months and many patients suffered from treatment toxicity without experiencing any benefit. Recent advances in molecular diagnosis have obliged doctors to move away from the one-size-fits-all approach. We have entered an era when the right treatment at the right time should be selected for each patient, aiming for maximal efficacy with minimal toxicity. The current issue of Asia-Pacific Journal of Clinical Oncology (APJCO) publishes five articles on personalized medicine for lung cancer that demonstrate the significant contribution made by Asian investigators in this arena. Tomita et al.1 reported on pre-operative evaluation of prognostic markers that included quantitative assessment of fluorodeoxyglucose on a positron emission tomography (PET) scan. The 5-year survival rate of patients with a pre-operative standardized uptake value (a high maximum standardized uptake value [SUVmax]) of >6.6 was significantly lower than in those with a low SUVmax (63 vs 87%, respectively, P = 0.0004). In addition, high pre-operative serum CEA was associated with a significantly worse survival than normal carcinoembryonic antigen (CEA) (51 vs 83%, P < 0.0001). Moreover, the combined use of pre-operative SUVmax and CEA level might be a strong prognostic marker for survival. These results are provocative but the study is limited by the small sample size and arbitrary definition of the cut-off value. SUV is a semi-quantitative measurement of tumor metabolic activity as reflected by glucose uptake. SUVmax on PET is a potential surrogate of cellular function while serum CEA could reflect tumor volume. However, in either case, a standardized cut-off value has never been recognized. This study generates an attractive hypothesis that needs to be validated in a large prospective study. Personalized therapy may also be applicable in patients with stage III locally advanced disease. Concurrent chemoradiation is the current standard therapy. Surgical resection after chemoradiation remains controversial. Isobe et al.2 are among the first to report on the importance of a complete pathological response to chemoradiotherapy for the long-term survival of patients with stage III NSCLC. Among 27 patients who had surgical resection after induction chemoradiotherapy seven attained a complete pathological response. The median survival of this small subset of patients was 77 months and six were still alive at the time of the report. Comparatively, the median survival of patients without a complete pathological response was significantly shorter. This finding is logical but the question is how we may apply this knowledge clinically. Surgical resection is not feasible for all patients; thus we need a surrogate. A post-chemoradiation decline in SUV on PET scan is correlated with pathological complete remission and favorable prognosis. A reduction in SUVmax of more than 80% was highly predictive of complete pathological response.3 However, what this study failed to address is whether surgical resection has added value to patients who already had a complete pathological response. If it does, PET could be a useful tool for selecting patients for surgical resection after chemoradiation. Activating mutations of the epidermal growth factor receptor (EGFR) gene represents the first predictive biomarker for the use of EGFR tyrosine kinase inhibitors (TKI) for patients with advanced stage metastatic lung cancer.4 While data supporting the clinical use of activating the EGFR mutation is overwhelming,5-8 universal testing is limited to major hospitals where EGFR mutation analysis is readily available. Many Asian centers still use clinical parameters, including histology and smoking status, as selection criteria. Wu et al.9 confirmed that the Chinese subgroup from the Iressa Pan-Asia Study (IPASS) share similar efficacy and safety with the overall study population. China enrolled the largest proportion of patients in IPASS (372 out of total of 1217) but provided the lowest proportion of tumor samples for biomarker analysis (38 vs 56% in the overall IPASS population). This has limited the statistical power of using the EGFR mutation as a predictive factor in this subgroup. In contrast, the other two studies by Liam et al. and Boyer et al.10, 11 did not attempt to collect tumor samples. TRUST is a phase IV prospective study on the use of erlotinib in an unselected NSCLC population.11 The tumor response rate was 28%. Progression-free and overall survival was 2.7 and 6.9 months, respectively. The Malaysian study is a retrospective analysis of patients with adenocarcinoma.10 The tumor response rate was 37% and median progression-free survival was 6.5 months. The differences in treatment outcomes to EGFR TKI between these studies is best explained by the difference in the incidence of the EGFR mutation in each study population. The incidence of the EGFR mutation in both the Chinese subgroup of IPASS and the Malaysian study is likely to be above 50%, while it is expected to be lower in the Australian population. These studies have reinforced the fact that patients should be selected by biomarkers and not according to clinical parameters. Personalized medicine is now standard for the management of lung cancer. EGFR mutation analysis is mandatory for selecting patients for EGFR TKI. For patients with early stage disease, a PET scan could be a useful tool to predict survival. We are clearly making steady progress in the management of NSCLC and the studies reported in this issue of APJCO contribute to these improvements.

Recent Advances in Molecular Diagnosis of Thyroid Cancer

Recent molecular studies have described a number of abnormalities associated with the progression and dedifferentiation of thyroid carcinoma. These distinct molecular events are often associated with specific stages of tumor development. In particular, remarkable advances have occurred in several major biological areas of thyroid cancer, including the molecular alterations for the loss of radioiodine avidity of thyroid cancer, the pathogenic role of the MAP kinase and PI3K/Akt pathways and their related genetic alterations, and the aberrant methylation of functionally important genes in thyroid tumorigenesis and pathogenesis. Recognition of these features is crucial to the management of patients with thyroid cancer. Novel treatments are being designed based on our enhanced understanding of this disease process.

Thyroid Function and Growth Regulation under Normal and Abnormal Conditions

The thyroid gland exerts a major control on the physiology of the whole body, and it raises fundamental questions about molecular physiological processes. Moreover, an increased proliferation of thyroid cells is associated with several pathologies, and several mechanisms may be involved. Thyroid disorders are very common, affecting millions of people. These include hypothyroidism, hyperthyroidism, thyroid nodules, thyroid cancer, and so forth, but they are also associated with other nonthyroid disorders. This special issue is devoted to illustrate the particular richness of current investigations in the field of thyroid function and growth regulation under normal and abnormal conditions. Although thyroid gland function is mainly under the control of pituitary TSH in normal conditions, other factors may also play a role in this process. Thyroid disease is more common in women than in men. Tania Weber Furlanetto and Ana Paula Santin reviewed the direct effects of estrogens on thyroid function and growth regulation in the paper titled “Role of estrogen in thyroid function and growth regulation.” Thyroid cancer is the most common endocrine malignancy, and its incidence has significantly risen in the last decades in the world. The knowledge how thyroid cancer develops is expanding rapidly. The sequential acquisition of mutations which arise as a consequence of damage to the genome is required in order to transform a normal cell into a malignant one. The understanding of the process of thyroid carcinogenesis at the molecular level will improve not only the diagnostic but also the treatment of this pathology. Ioannis Legakis and Konstantinos Syrigos describe the molecular events associated with the progression and dedifferentiation of thyroid carcinoma in the paper titled “Recent advances in molecular diagnosis of thyroid cancer.” Thyroid-specific transcription factors regulate thyroid-specific gene expression and organogenesis. Their possible role in thyroid cancer as well as in the maintenance and/or activity of stem cells is discussed by Shioko Kimura in the paper titled “Thyroid-specific transcription factors and their roles in thyroid cancer.” MicroRNAs (miRNAs) are short ribonucleic acid molecules (around 22 nucleotides) found in eukaryotic cells. miRNAs are posttranscriptional regulators that bind to complementary sequences on messenger RNA transcripts inducing the translational repression or messenger RNA degradation. Several miRNAs have been found to have links with some types of cancer. Francesca Marini, Ettore Luzi, and Maria Luisa Brandi reviewed the role of miRNAs in thyroid cancer development in the paper titled “MicroRNA role in thyroid cancer development.” Growth factors play a role in thyroid proliferation and function, while EGF acts as a mitogen for thyroid cells inhibiting also thyroid differentiation. TGF-β is a potent inhibitor of thyroid cell growth. However, in some transformed thyroid cells this inhibition is lost. The role of TGF-β and EGF on thyroid carcinogenesis and the crosstalk between these growth factors are discussed by Gabriella Mincione Maria Carmela Di Marcantonio, Chiara Tarantelli, Sonia D'Inzeo, Arianna Nicolussi, Francesco Nardi, Caterina Francesca Donini, and Anna Coppa in the paper titled “EGF and TGF-β1 effects on thyroid function.” Grave's disease and Hashimoto's thyroiditis are the two main types of autoimmune thyroid disease. Occasionally they are also associated with other autoimmune diseases. Emina Kasumagic-Halilovic, Asja Prohic, Begler Begovic, and Nermina Ovcina-Kurtovic bring additional support to the existence of a significant association between vitiligo and thyroid autoimmunity in the paper titled “Association between vitiligo and thyroid autoimmunity.” Although some authors have found an association between an abnormal thyroid condition and bipolar disorder, little is known about the implication of the hypothalamo-pituitary-thyroid in neuropsychological deficits. Subho Chakrabarti review the last findings on this topic including genetic and neuroimaging investigations (Thyroid Functions and Bipolar Affective Disorder). Guillermo Juvenal Daniel Christophe Pierre Roger Mario Pisarev

The Wobbly Child: An Approach to Inherited Ataxias

Genetic causes of ataxia are numerous. These disorders often present in the pediatric population, and finding a precise diagnosis can be quite challenging. Recent advances in molecular diagnosis make it difficult for the clinician to determine what investigations to undertake and in which order. This article presents 3 cases of pediatric onset ataxia with a genetic basis that will help to formulate and show a practical approach to this important clinical problem.

Challenges in Brucella bacteraemia

Brucella possesses unique historical, epidemiological, phylogenetic and pathogenetic characteristics that constantly reinforce the pathogen's place at the epicentre of scientific interest. One such unique characteristic is the significance of bacteraemia in the course of the disease. Bacteraemia in brucellosis may be periodically present, of limited practical diagnostic importance, and of doubtful significance as an index of bacteriological cure. On the other hand, recognition of bacteraemia augments prognosis, typing and biotyping (and thus further research). Recent advances in molecular diagnosis with the help of real time polymerase chain reaction (rtPCR) have shown that bacteraemia in brucellosis may persist, at culture non-detectable levels, for protracted periods even after apparent clinical cure. This raises important issues for future research, implying that the pathogen may actually be non-eradicable.