Reduced functional resting-state connectivity in chronic pain patients with small fiber neuropathy.

Chronic neuropathic pain can lead to structural and functional brain reorganization. Neuropathic pain, the main symptom of small fiber neuropathy (SFN), may be linked to specific brain biosignatures. Functional connectivity changes during resting state (RS) have been observed in SFN patients, but little is known about these changes in idiopathic SFN.

Microneurographic portrait of 19 patients with small fiber neuropathy-A pilot study.

Small fiber neuropathy (SFN) is defined by dysfunction or degeneration of Aδ and C fibers, causing impaired temperature perception and spontaneous neuropathic pain. We performed microneurography (MNG) to analyze C-nociceptor properties in 19 patients with SFN. C-nociceptors were classified as mechanosensitive or mechano-insensitive, and either "normal," "hyperactive," or "hypoactive.

Genetic Variants and Clinical Phenotyping in 39 Pediatric Patients with Neuropathic Pain.

Pathogenic variants in voltage-gated sodium channels (VGSCs) may cause disturbed sensory function, including small fiber neuropathy (SFN) in adults, but little is known about their role in children and adolescents.A total of 39 prospectively enrolled children (age 12.03 ± 4.

Diagnostic Use of Genome Sequencing in Patients With 11p15.5 Imprinting Disorder Features: A Pilot Study.

To assess the suitability of genome sequencing (GS) as the second step in the diagnostics of patients with the features of 11p15.5-associated imprinting disorders (ImpDis: Silver-Russell syndrome [SRS], Beckwith-Wiedemann syndrome [BWS]), we performed short-read GS in patients negatively tested for imprinting disturbances. Obtaining a genetic diagnosis for patients with the features of these syndromes is challenging due to the clinical and molecular heterogeneity and overlap, and many patients remain undiagnosed after the currently suggested stepwise diagnostic workup.

Painful stimulation increases functional connectivity between supplementary motor area and thalamus in patients with small fibre neuropathy.

Background: The lead symptom of small fibre neuropathy (SFN) is neuropathic pain. Recent functional magnetic resonance imaging (fMRI) studies have indicated central changes in SFN patients of different etiologies. However, less is known about brain functional connectivity during acute pain processing in idiopathic SFN.

[Sequence variants of unknown significance in small fiber neuropathy : Characterization of a heterogeneous patient population].

Background: In almost half of patients suffering from small fiber neuropathies (SFN), the etiology remains elusive. For these patients with "idiopathic SFN", symptomatic analgesic therapy is the only option. Reports on a potential genetic background of neuropathic pain syndromes are increasing and particularly in SFN patients, several genetic variants were found mainly located in genes encoding voltage-gated sodium channels.

Reduced Gray Matter Volume and Cortical Thickness in Patients With Small-Fiber Neuropathy.

Small-fiber neuropathy (SFN) is defined by degeneration or dysfunction of peripheral sensory nerve endings. Central correlates have been identified on the level of gray matter volume (GMV) and cortical thickness (CT) changes. However, across SFN etiologies knowledge about a common structural brain signature is still lacking.

Peripheral temperature dysregulation associated with functionally altered Na1.8 channels.

The voltage-gated sodium channel Na1.8 is prominently expressed in the soma and axons of small-caliber sensory neurons, and pathogenic variants of the corresponding gene SCN10A are associated with peripheral pain and autonomic dysfunction. While most disease-associated SCN10A variants confer gain-of-function properties to Na1.

Genetic pain loss disorders.

Genetic pain loss includes congenital insensitivity to pain (CIP), hereditary sensory neuropathies and, if autonomic nerves are involved, hereditary sensory and autonomic neuropathy (HSAN). This heterogeneous group of disorders highlights the essential role of nociception in protecting against tissue damage. Patients with genetic pain loss have recurrent injuries, burns and poorly healing wounds as disease hallmarks.

Single Cell Genetic Profiling of Tumors of Breast Cancer Patients Aged 50 Years and Older Reveals Enormous Intratumor Heterogeneity Independent of Individual Prognosis.

Purpose: Older breast cancer patients are underrepresented in cancer research even though the majority (81.4%) of women dying of breast cancer are 55 years and older. Here we study a common phenomenon observed in breast cancer which is a large inter- and intratumor heterogeneity; this poses a tremendous clinical challenge, for example with respect to treatment stratification.

Hard wiring of normal tissue-specific chromosome-wide gene expression levels is an additional factor driving cancer type-specific aneuploidies.

Background: Many carcinomas have recurrent chromosomal aneuploidies specific to the tissue of tumor origin. The reason for this specificity is not completely understood.

Methods: In this study, we looked at the frequency of chromosomal arm gains and losses in different cancer types from the The Cancer Genome Atlas (TCGA) and compared them to the mean gene expression of each chromosome arm in corresponding normal tissues of origin from the Genotype-Tissue Expression (GTEx) database, in addition to the distribution of tissue-specific oncogenes and tumor suppressors on different chromosome arms.

The impact of CBP expression in estrogen receptor-positive breast cancer.

Background: The development of new biomarkers with diagnostic, prognostic and therapeutic prominence will greatly enhance the management of breast cancer (BC). Several reports suggest the involvement of the histone acetyltransferases CREB-binding protein (CBP) and general control non-depressible 5 (GCN5) in tumor formation; however, their clinical significance in BC remains poorly understood. This study aims to investigate the value of CBP and GCN5 as markers and/or targets for BC prognosis and therapy.

Genome Instability Profiles Predict Disease Outcome in a Cohort of 4,003 Patients with Breast Cancer.

Purpose: The choice of therapy for patients with breast cancer is often based on clinicopathologic parameters, hormone receptor status, and amplification. To improve individual prognostication and tailored treatment decisions, we combined clinicopathologic prognostic data with genome instabilty profiles established by quantitative measurements of the DNA content.

Experimental Design: We retrospectively assessed clinical data of 4,003 patients with breast cancer with a minimum postoperative follow-up period of 10 years.

High Levels of Chromosomal Copy Number Alterations and TP53 Mutations Correlate with Poor Outcome in Younger Breast Cancer Patients.

Prognosis in young patients with breast cancer is generally poor, yet considerable differences in clinical outcomes between individual patients exist. To understand the genetic basis of the disparate clinical courses, tumors were collected from 34 younger women, 17 with good and 17 with poor outcomes, as determined by disease-specific survival during a follow-up period of 17 years. The clinicopathologic parameters of the tumors were complemented with DNA image cytometry profiles, enumeration of copy numbers of eight breast cancer genes by multicolor fluorescence in situ hybridization, and targeted sequence analysis of 563 cancer genes.

Spatial UBE2N protein expression indicates genomic instability in colorectal cancers.

Background: One major hallmark of colorectal cancers (CRC) is genomic instability with its contribution to tumor heterogeneity and therapy resistance. To facilitate the investigation of intra-sample phenotypes and the de novo identification of tumor sub-populations, imaging mass spectrometry (IMS) provides a powerful technique to elucidate the spatial distribution patterns of peptides and proteins in tissue sections.

Methods: In the present study, we analyzed an in-house compiled tissue microarray (n = 60) comprising CRCs and control tissues by IMS.

Complement-Activating Capacity of Autoantibodies Correlates With Disease Activity in Bullous Pemphigoid Patients.

Bullous pemphigoid is a subepidermal blistering skin disease, associated with autoantibodies to hemidesmosomal proteins, complement activation at the dermal-epidermal junction, and dermal granulocyte infiltration. Clinical and experimental laboratory findings support conflicting hypotheses regarding the role of complement activation for the skin blistering induced by pemphigoid autoantibodies. In-depth studies on the pathogenic relevance of autoimmune complement activation in patients are largely lacking.

Molecular diagnosis of anti-laminin 332 (epiligrin) mucous membrane pemphigoid.

Background: Mucous membrane pemphigoid is a group of chronic subepithelial autoimmune blistering diseases that mainly affect mucous membranes. Laminin 332-specific autoantibodies are present in approximately 1/3 of the patients, being associated with an increased risk of malignancy. Because of the severe complications, an early recognition of the disease allowing a timely therapy is essential.