Paraneoplastic brainstem encephalomyelitis and atypical form of chronic inflammatory demyelinating polyneuropathy in patient with testicular germinal tumor—Is this an overlap syndrome? A case report

Paraneoplastic neurologic syndromes are diagnosed when neurologic symptoms are associated with neoplasm and other causative factors are excluded. They may precede or be simultaneous to various types of neoplasms, mainly malignant. In men up to 45–50 years old the most common cancer causing the paraneoplastic syndrome is testicle tumor, manifesting usually as limbic/brain stem encephalitis and myelitis. Usually effective treatment of underlying neoplasm brings resolution of neurologic symptoms. But corticosteroids and intravenuous immunoglobulins are also used. In the presented case a 37-year-old man was primarily diagnosed and treated for progressive tetraparesis with signs of both upper and lower motor neuron dysfunction, associated with bulbar symptoms. Having various diagnostic procedures performed an atypical form of chronic inflammatory demyelinating polyradiculoneuronopathy was primarily suspected, but eventually a discovery of endodermal sinus tumor in the testicle enabled to state the diagnosis of possible paraneoplastic syndrome. In spite of chemotherapy the patient died shortly after the diagnosis because of infectious complications. Histopathology displayed intense inflammatory changes in the brain stem as well as in cranial nerves and cervical spinal cord. The same immunological process evoked by various pathogenetic factors (infection vs. neoplasm) may cause similar clinical picture and hinder the diagnosis. Most importantly it may delay the proper way of treatment

Cerebral amyloid angiopathy-related inflammation – A case report presenting diagnostic difficulties

We describe an 86-year-old woman with a history of hypertension who presented sudden disturbances of consciousness and left hemiparesis. Brain magnetic resonance imaging (MRI) revealed diffused hyperintensive changes on T2-weighted images localized subcortically in the white matter of both cerebral hemispheres, corresponding to acute vasogenic edema, causing moderate mass effect. Posterior reversible encephalopathy syndrome was initially diagnosed. After implementation of anti-edema intravenous steroid treatment and hypotensive therapy the symptoms began to retire, till the total regression. The successive hospitalizations took place two and eight months later due to the occurrence of seizures, motor deficits and the development of mild cognitive impairment. Brain MRI revealed progression of the white matter changes and diffused subcortical microhemorrhages. Each time pulse steroid therapy was implemented and the symptoms improved significantly after several days. Chronic oral steroid treatment resulted in the stabilization of neurological status. The long-term observation of clinical symptoms, remission after immunosuppressive therapy and white matter changes with subcortical microhemorrhages in brain MRI leaded to the diagnosis of cerebral amyloid angiopathy-related inflammation

Stearoyl-CoA desaturase 1 activity determines the maintenance of DNMT1-mediated DNA methylation patterns in pancreatic β\beta-Cells

Metabolic stress, such as lipotoxicity, affects the DNA methylation profile in pancreatic β-cells and thus contributes to β-cell failure and the progression of type 2 diabetes (T2D). Stearoyl-CoA desaturase 1 (SCD1) is a rate-limiting enzyme that is involved in monounsaturated fatty acid synthesis, which protects pancreatic β-cells against lipotoxicity. The present study found that SCD1 is also required for the establishment and maintenance of DNA methylation patterns in β-cells. We showed that SCD1 inhibition/deficiency caused DNA hypomethylation and changed the methyl group distribution within chromosomes in β-cells. Lower levels of DNA methylation in SCD1-deficient β-cells were followed by lower levels of DNA methyltransferase 1 (DNMT1). We also found that the downregulation of SCD1 in pancreatic β-cells led to the activation of adenosine monophosphate-activated protein kinase (AMPK) and an increase in the activity of the NAD-dependent deacetylase sirtuin-1 (SIRT1). Furthermore, the physical association between DNMT1 and SIRT1 stimulated the deacetylation of DNMT1 under conditions of SCD1 inhibition/downregulation, suggesting a mechanism by which SCD1 exerts control over DNMT1. We also found that SCD1-deficient β-cells that were treated with compound c, an inhibitor of AMPK, were characterized by higher levels of both global DNA methylation and DNMT1 protein expression compared with untreated cells. Therefore, we found that activation of the AMPK/SIRT1 signaling pathway mediates the effect of SCD1 inhibition/deficiency on DNA methylation status in pancreatic β-cells. Altogether, these findings suggest that SCD1 is a gatekeeper that protects β-cells against the lipid-derived loss of DNA methylation and provide mechanistic insights into the mechanism by which SCD1 regulates DNA methylation patterns in β-cells and T2D-relevant tissues

Recent achievements in transcatheter closure of ventricular septal defects : a systematic review of literature and a meta-analysis

Background: Ventricular septal defect (VSD) is one of the most common congenital heart defects. Currently, surgery remains the treatment of choice. However, transcatheter techniques for closing of various types of VSDs have become an alternative. Aims: The objective of our study was to present the outcomes of transcatheter closure of various types of VSD based on a systematic review of recent publications. Methods: A systematic review of studies published in English between January 2014 and March 2020 was performed using the PubMed database (MEDLINE) independently by 2 reviewers. Data on success and complication rates were extracted. Studies including fewer than 5 patients and those with acquired VSD were excluded from the analysis. Results: Finally, 44 studies were included for analysis, with a total number of 4050 patients. The pooled estimate of the overall success rate based on the random effects model was 97.96% (95% CI, 97.37–98.56; Q test P 0.99; I 2 = 0%) for permanent VSD. Conclusions: Transcatheter closure of selected VSDs appears to be an effective and safe method of treatment. Recent studies have shown high rates of successful interventions with a low incidence of complications

Identification of the first in Poland CACNA1A gene mutation in familial hemiplegic migraine. Case report

Introduction Migraine is a common neurological disorder characterized by a particular phenotype, complex pathophysiology and a heterogeneous genetic background. Among several heritable forms, familial hemiplegic migraine is the best described one. In the majority of cases it is caused by mutations in one of three different genes. Case report Clinical symptoms of a 47 year old proband (and independently described in his 20 year old son) as well as differential diagnosis are discussed in the presented report. The most characteristic were recurrent attacks of blurred vision, paresthesias and hemiparesis often accompanied by speech disturbances and followed by severe headache with vomiting. Advanced morphological and genetic procedures were required to exclude MELAS, CADASIL and Call-Fleming syndrome. Finally, the definite diagnosis was possible after the application of the whole exome sequencing technique. It confirmed, for the first time in the Polish population, a heterozygous T666M mutation (c.1997C>T; p.Thr666Met) in the CACNA1A gene in the proband, the proband's son and in several other family members. Conclusion The presented report provides clinical and genetic insight into familial hemiplegic migraine 1 resulting from a mutation in the CACNA1A gene

Comparison of Changes in the Lipid Profile of Postmenopausal Women With Early Stage Breast Cancer Treated With Exemestane or Letrozole

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97162/1/0091270011424153.pd

High-Throughput Approaches onto Uncover (Epi)Genomic Architecture of Type 2 Diabetes

Type 2 diabetes (T2D) is a complex disorder that is caused by a combination of genetic, epigenetic, and environmental factors. High-throughput approaches have opened a new avenue toward a better understanding of the molecular bases of T2D. A genome-wide association studies (GWASs) identified a group of the most common susceptibility genes for T2D (i.e., TCF7L2, PPARG, KCNJ1, HNF1A, PTPN1, and CDKAL1) and illuminated novel disease-causing pathways. Next-generation sequencing (NGS)-based techniques have shed light on rare-coding genetic variants that account for an appreciable fraction of T2D heritability (KCNQ1 and ADRA2A) and population risk of T2D (SLC16A11, TPCN2, PAM, and CCND2). Moreover, single-cell sequencing of human pancreatic islets identified gene signatures that are exclusive to α-cells (GCG, IRX2, and IGFBP2) and β-cells (INS, ADCYAP1, INS-IGF2, and MAFA). Ongoing epigenome-wide association studies (EWASs) have progressively defined links between epigenetic markers and the transcriptional activity of T2D target genes. Differentially methylated regions were found in TCF7L2, THADA, KCNQ1, TXNIP, SOCS3, SREBF1, and KLF14 loci that are related to T2D. Additionally, chromatin state maps in pancreatic islets were provided and several non-coding RNAs (ncRNA) that are key to T2D pathogenesis were identified (i.e., miR-375). The present review summarizes major progress that has been made in mapping the (epi)genomic landscape of T2D within the last few years

The Crooked Logic of Migration Policies and Their Malthusian Roots

European perspectives on recent migration fl ows are heavily biased towards the Malthusian and evolutionist view of many classical western social thinkers. Although it may serve as a purely descriptive tool to outline the present relations between Europe and the outside world (specifi cally the Middle East and North Africa), it certainly doesnot provide any solid base for designing projects which might free human beings from further subjugation, poverty and entrenched inequality – precisely the reasons behind the recent migration crisis to the EU. We argue here that the way the EU perceives and deals with the recent fl ow of migrants (refugees and others) is based on an outdated perception that does not allow for providing valid solutions to real problems. Therefore we present the undercurrent logic behind the political designs, point out defi ciencies, and illustrate a possible new approach by discussing the EU’s migration policy and border management, as linked to the EU security and defence policy. The current migration crisis would never have emerged if not for the lack of stability in the Middle East and North Africa, which neither the EU nor UN nor NATO was ready or able to remedy. The beginning of putting together a viable EU migration policy and border regime will depend on rethinking the security policy, decision-making and capacity, and abandoning the Malthusian perception of the world is a start

High-Throughput Approaches onto Uncover (Epi)Genomic Architecture of Type 2 Diabetes

Type 2 diabetes (T2D) is a complex disorder that is caused by a combination of genetic, epigenetic, and environmental factors. High-throughput approaches have opened a new avenue toward a better understanding of the molecular bases of T2D. A genome-wide association studies (GWASs) identified a group of the most common susceptibility genes for T2D (i.e., TCF7L2, PPARG, KCNJ1, HNF1A, PTPN1, and CDKAL1) and illuminated novel disease-causing pathways. Next-generation sequencing (NGS)-based techniques have shed light on rare-coding genetic variants that account for an appreciable fraction of T2D heritability (KCNQ1 and ADRA2A) and population risk of T2D (SLC16A11, TPCN2, PAM, and CCND2). Moreover, single-cell sequencing of human pancreatic islets identified gene signatures that are exclusive to α-cells (GCG, IRX2, and IGFBP2) and β-cells (INS, ADCYAP1, INS-IGF2, and MAFA). Ongoing epigenome-wide association studies (EWASs) have progressively defined links between epigenetic markers and the transcriptional activity of T2D target genes. Differentially methylated regions were found in TCF7L2, THADA, KCNQ1, TXNIP, SOCS3, SREBF1, and KLF14 loci that are related to T2D. Additionally, chromatin state maps in pancreatic islets were provided and several non-coding RNAs (ncRNA) that are key to T2D pathogenesis were identified (i.e., miR-375). The present review summarizes major progress that has been made in mapping the (epi)genomic landscape of T2D within the last few years