Abstracts presented at the 27th Annual Congress of the Belgian Society of Internal Medicine, 1-2 December 2023, Dolce La Hulpe, La Hulpe, Belgium

peer reviewedIntroduction: The term pseudohypoparathyroidism was introduced in 1942 by Albright et al. to describe several patients presenting hypocalcemia and hyperphosphatemia in association with short stature, short metacarpals and metatarsals, obesity as well as neurocognitive impairment (1). These findings are now referred as Albright’s hereditary osteodystrophy (AHO). Autoimmune polyendocrinopathy is characterized by autoimmune activity against more than one endocrine organ. We herein present a family (the mother and the daughter) affected with AHO and autoimmune polyendocrinopathy features. We show some preliminary genetic studies. Case reports: The index case is a 69 years old woman (patient A) , measuring 1m 47 and weighting 58 kg. She was diagnosed with Hashimoto Thyroiditis in 1982 and Biermer disease in 1982 (autoimmune polyendocrinopathy type 3, see table 1). Because of muscle cramps, biological investigation revealed in 2010: serum calcium: 2.10 mmol/L (2.15-2.6), phosphates: 1.08 mmol/L (0.74-1.51), PTH: 187 pg/ml, 25 vitD: 35 ng/ml (>20 ), IGF1: 114 ng/ml (32-226), GH: 0.7 ng/ml. In 2018, AHO was suspected on the basis of hypocalcemia, short stature and bilateral short 4th and 5th metacarpals and phalanges. Osteodensitometry was normal. GNAS gene sequencing identified a novel heterozygous variant c.970 56GT>T (class III). In silico analysis predict splicing defects. Her daughter (Patient B) is 47 years old, measures 1m45 and weights 41 kg. She was diagnosed with Hashimoto Thyroiditis in 1989. Biological investigations revealed: serum calcium: 2.10 mmol/L (2.15-2.6), phosphates: 1.2 mmol/L (0.74-1.51), PTH: 131 pg/ml, 25 vitD: 24 ng/ml (>20 ). She presented Raynaud’s phenomenon and cryoglobulinemia in 2022. Because of short stature, brain calcifications, and bilateral short 4th and 5th metacarpals, autosomal dominant AHO is also suspected. Genetic analysis is ongoing. Conclusion: AHO is caused by mutations and/or epigenetic changes at the complex of GNAS locus on chromosome 20q13.3. It is an underdiagnosed cause of paresthesias and Fahr’s disease. Heterozygous maternal GNAS mutations cause variable degrees of PTH resistant hypocalcemia. Reduced Gsa activity may result in loss of endocrine function, and can develop resistance to other hormones including TSH, GH, gonadotropins, and calcitonin. The combination of AHO and autoimmune polyendocrinopathies is very rar

Study of High-Performance Engineering Polymers Applied In Reciprocating Hermetic Refrigeration Compressors

Manufacturers of hermetic refrigeration compressors for domestic and commercial applications have been increasing the energy efficiency of their products systematically over the last decades through the continuous efforts of in-house research groups, universities and suppliers. This joint effort encompasses the technical fields of design, materials, processes, manufacturing, and simulation techniques, to achieve a multidisciplinary approach to compressor optimization as applied to refrigeration systems. Gains such as increased efficiency of the electric motor, reduction of bearing friction power loss, minimizing back flow on valves have already been addressed and the continuous search for new approaches have been proposed. This work presents a study of energy efficiency gain by comparing low conduction heat transfer plastic materials to metallic materials used in current compressor designs. The components compared include the cylinder head, discharge muffler, shock loop, valve plate and crankcase. The energy efficiency gain was evaluated using the Coefficient of Performance (COP) through the use of the Conjugate Heat Transfer (CHT) model using superheating temperature. The CHT model temperature results were compared with the values measured by an instrumented compressor. To complement the study, the parts and assemblies were structurally evaluated using the finite element method under performance and durability test operating conditions. The feasibility of the mold filling process was verified, because the final design of the components must be a compromise between functional requirements and process solution. In conclusion, the results show that significant efficiency gains can be achieved through the use of engineering thermoplastic. This is achieved through careful material selection and proper design that considers not only material properties, but material and process costs using the flexibility of injection molding to group parts and subsystems

Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation

Analyses of 32 Loci Clarify Phylogenetic Relationships among Trypanosoma cruzi Lineages and Support a Single Hybridization prior to Human Contact

Trypanosoma cruzi is the protozoan parasite that causes Chagas disease, a major health problem in Latin America. The genetic diversity of this parasite has been traditionally divided in two major groups: T. cruzi I and II, which can be further divided in six major genetic subdivisions (subgroups TcI-TcVI). T. cruzi I and II seem to differ in important biological characteristics, and are thought to represent a natural division relevant for epidemiological studies and development of prophylaxis. Having a correct reconstruction of the evolutionary history of T. cruzi is essential for understanding the potential connection between the genetic and phenotypic variability of T. cruzi with the different manifestations of Chagas disease. Here we present results from a comprehensive phylogenetic analysis of T. cruzi using more than 26 Kb of aligned sequence data. We show strong evidence that T. cruzi II (TcII-VI) is not a natural evolutionary group but a paraphyletic lineage and that all major lineages of T. cruzi evolved recently (<3 million years ago [mya]). Furthermore, the sequence data is consistent with one major hybridization event having occurred in this species recently (< 1 mya) but well before T. cruzi entered in contact with humans in South America

Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia in middle-income countries

Background: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. Aims: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. Methods: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). Results: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteria, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20–37) versus 47 (IQR 32–58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11–40]) than in HICs (44/102 [43%, 95% CI 34–53], p = 0.039). Conclusions: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.</p

Dynamic Effective Connectivity of Inter-Areal Brain Circuits

Anatomic connections between brain areas affect information flow between neuronal circuits and the synchronization of neuronal activity. However, such structural connectivity does not coincide with effective connectivity (or, more precisely, causal connectivity), related to the elusive question “Which areas cause the present activity of which others?”. Effective connectivity is directed and depends flexibly on contexts and tasks. Here we show that dynamic effective connectivity can emerge from transitions in the collective organization of coherent neural activity. Integrating simulation and semi-analytic approaches, we study mesoscale network motifs of interacting cortical areas, modeled as large random networks of spiking neurons or as simple rate units. Through a causal analysis of time-series of model neural activity, we show that different dynamical states generated by a same structural connectivity motif correspond to distinct effective connectivity motifs. Such effective motifs can display a dominant directionality, due to spontaneous symmetry breaking and effective entrainment between local brain rhythms, although all connections in the considered structural motifs are reciprocal. We show then that transitions between effective connectivity configurations (like, for instance, reversal in the direction of inter-areal interactions) can be triggered reliably by brief perturbation inputs, properly timed with respect to an ongoing local oscillation, without the need for plastic synaptic changes. Finally, we analyze how the information encoded in spiking patterns of a local neuronal population is propagated across a fixed structural connectivity motif, demonstrating that changes in the active effective connectivity regulate both the efficiency and the directionality of information transfer. Previous studies stressed the role played by coherent oscillations in establishing efficient communication between distant areas. Going beyond these early proposals, we advance here that dynamic interactions between brain rhythms provide as well the basis for the self-organized control of this “communication-through-coherence”, making thus possible a fast “on-demand” reconfiguration of global information routing modalities

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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