Identification of a new familial case of 3q29 deletion syndrome associated with cleft lip and palate via whole-exome sequencing

Many unbalanced large copy number variants reviewed in the paper are associated with syndromic orofacial clefts, including a 1.6 Mb deletion on chromosome 3q29. The current report presents a new family with this recurrent deletion identified via whole-exome sequencing and confirmed by array comparative genomic hybridization. The proband exhibited a more severe clinical phenotype than his affected mother, comprising right-sided cleft lip/alveolus and cleft palate, advanced dental caries, heart defect, hypospadias, psychomotor, and speech delay, and an intellectual disability. Data analysis from the 3q29 registry revealed that the 3q29 deletion increases the risk of clefting by nearly 30-fold. No additional rare and pathogenic nucleotide variants were identified that could explain the clefting phenotype and observed intrafamilial phenotypic heterogeneity. These data suggest that the 3q29 deletion may be the primary risk factor for clefting, with additional genomic variants located outside the coding sequences, methylation changes, or environmental exposure serving as modifiers of this risk. Additional studies, including whole-genome sequencing or methylation analyses, should be performed to identify genetic factors underlying the phenotypic variation associated with the recurrent 3q29 deletion.     

Primary and acquired drug resistance of tuberculosis bacilli in Poland

Information about resistant pattern of Mycobacterium tuberculosis isolates against antituberculon drugs is a very important part of tuberculosis control and indicates the directions of TB policy in each country. Poland joined WHO/IUATLD global project on drug resistance surveillance, and carried out the first prospective survey, simultaneously on primary and acquired drug resistance of tuberculosis patients according WHO/IUATLD recommendations. The programme covered the whole country, basing on cooperation between the National Reference Laboratory (NRL) with regional TB laboratories. Questionnaires and cultures were obtained from patients who excreted TB bacilli during the period from 1 November 1996 to 1 November 1997 (12 months). Drug susceptibility testing to INH, SM, EMB and RMP were performed on Lowenstein-Jensen medium according to the proportion method or/and radiometric Bactec 460 TB system. 3970 TB patients bacteriologically confirmed by culture were included in a one-year study. The male to female ratio was 2.6:1. Patients were at the age of 6 to 83 years. Majority of patients (86% males and 77% of females) was older than 35 years. Primary resistance to any drug was found in 3.6% of new cases and 2.4% of those patients who excreted monoresistant strains. No monoresistance to EMB was found. 18 patients (0.6%) were infected by MDR strains. Total resistance in new cases was for INH--2.6%, for SM--1.8%, for RMP--0.7% and for EMB--0.1%. Acquired resistance to any drug was found in 17.0% of treated. Majority of patients--7.7% excreted monoresistant strains. 7.0% were infected by MDR strains. Total resistance to INH was 14.8%, to SM--9.2%, to RMP--7.8%, and to EBM--2.5%. No correlation was found between sex and primary resistance rates. Among new cases, 3.7% of males and 3.3% of females were infected with resistant strains. However, among treated patients, males (20%) excreted resistant strains twice as much as females (9.1%). Mean age of women and men infected with primary and acquired resistant strains was similar.     

Computed tomography (CT) evaluation of breast cancer patients with osteolytic bone metastases undergoing palliative radiotherapy—a feasibility study

Twenty-five patients with osteolytic metastases had computed tomography (CT) scans before and 3 months after palliative radiotherapy. The median % density change following single 8 Gy, 20 Gy/5#, 30 Gy/10# were: 128 (range 98–255), 141 (79–342), and 145 (65–235), respectively. It is feasible to evaluate remineralization of osteolytic lesions with palliative radiotherapy.     

Type I insulin-like growth factor receptor function in breast cancer

Experimental evidence suggests an important role of the type I IGF receptor (IGF-IR) in breast cancer development. Breast tumors and breast cancer cell lines express the IGF-IR. IGF-IR levels are higher in cancer cells than in normal breast tissue or in benign mammary tumors. The ligands of the IGF-IR are potent mitogens promoting monolayer and anchorage-independent growth of breast cancer cells. Interference with IGF-IR activation, expression, or signaling inhibits growth and induces apoptosis in breast cancer cells. In addition, recent studies established the involvement of the IGF-IR in the regulation of breast cancer cell motility and adhesion. We have demonstrated that in MCF-7 cells, overexpression of the IGF-IR promotes E-cadherin-dependent cell aggregation, which is associated with enhanced cell proliferation and prolonged survival in three-dimensional culture.The expression or function of the IGF-IR in breast cancer cells is modulated by different humoral factors, such as estrogen, progesterone, IGF-II, and interleukin-1. The IGF-IR and the estrogen receptor (ER) are usually co-expressed and the two signaling systems are engaged in a complex functional cross-talk controlling cell proliferation.Despite the convincing experimental evidence, the role of the IGF-IR in breast cancer etiology, especially in metastatic progression, is still not clear. The view emerging from cellular and animal studies is that abnormally high levels of IGF-IRs may contribute to the increase of tumor mass and/or aid tumor recurrence, by promoting proliferation, cell survival, and cell-cell interactions. However, in breast cancer, except for the well established correlation with ER status, the associations of the IGF-IR with other prognostic parameters are still insufficiently documented.     

Influence of Amodiaquine on the Antimalarial Activity of Ellagic Acid: Crystallographic and Biological Studies

In the search for new antimalarial drugs, design of hybrid molecules is recommended to improve biological activity and to decrease the risk of parasite resistance development. Ellagic acid, as an inhibitor of Plasmodium glutathione, presents an original mode of action and thus appears as a promising antiplasmodial compound. A new complex (AQ–EA) consisting of the well‐known antimalarial drug, amodiaquine, and ellagic acid was obtained. The studied crystal structure of AQ–EA showed that the triclinic centrosymmetrical unit cell of the crystal contains two molecules of amodiaquine (AQ) and two symmetrically independent molecules of ellagic acid (EA). The packing of the molecules in the crystal is dominated by hydrogen bonds between AQ and EA. The antiplasmodial activity of the hybrid complex AQ–EA was also determined and compared with the values of IC₅₀ for AQ and EA separately. Potentiation assays between both molecules were conducted to understand the pharmacological interactions between AQ and EA against Plasmodium falciparum in vitro. The hybrid complex AQ–EA (IC₅₀ of 47 nm ) showed improved antiplasmodial activity in comparison with EA alone.     

Feasibility and clinical utility of real-time tele-echocardiography using personal mobile device-based pocket echocardiograph

IntroductionRecently introduced microUSB ultrasound probe, which can be connected to personal mobile device constitutes a new class of diagnostic pocket size imaging devices (PSID).The aim of this study was to assess the feasibility and clinical utility of real-time tele-echocardiography with the use such device.Material and methodsThe study group comprised 30 patients (18 men and 12 women; mean age: 54 ±14 years; mean body mass index: 27 ±6 kg/m²), admitted to various hospital departments (infectious diseases, internal medicine and cardiology). All patients underwent focused echocardiographic examination performed by an inexperienced operator using PSID and collaborating remotely in real-time with cardiologist by means of tele-consultation. Before commencing the examination, the operators underwent 1 h training in use of the PSID.ResultsIn most of patients PSID imaging provided sufficient diagnostic image quality. The dimensions of left ventricle, left atrium and the aorta obtained during the this examination showed good correlation with standard echocardiography (r = 0.89, r = 0.82, r = 0.92 respectively), but the correlation for TAPSE measurements was less pronounced (r = 0.52). The agreement in detection of pathologies (wall motion abnormalities, morphological and functional valvular abnormalities) between the tele-echocardiography and standard echocardiographic examination was good to very good (κ ranged from 0.648 to 0.823).ConclusionsPocket size imaging devices allows an inexperienced operator to perform a focused echocardiographic examination under a remote supervision of an experienced cardiologist. The introduction of new technology in the form of PSID with tele-echocardiography feature can revolutionize access to this imaging technique.     

Enhanced Production of Biogas Using Biochar–Sulfur Composite in the Methane Fermentation Process

The methane fermentation of organic waste is one way to minimize organic waste, which accounts for 77% of the global municipal waste stream. The use of biochar as an additive for methane fermentation has been shown to increase the production potential of biogas. Sulfur waste has a potential application to synergistic recycling in a form of composites with other materials including biochar. A composite product in the form of a mixture of biochar and molten sulfur has been proposed. In this experiment, additions of the sulfur–biochar composite (SBC) were tested to improve the fermentation process. The biochar was produced from apple chips under the temperature of 500 °C. The ground biochar and sulfur (<1 mm particle size) were mixed in the proportion of 40% biochar and 60% sulfur and heated to 140 °C for sulfur melting. After cooling, the solidified composite was ground. The SBC was added in the dose rate of 10% by dry mass of prepared artificial kitchen waste. Wet anaerobic digestion was carried out in the batch reactors under a temperature of 37 °C for 21 days. As an inoculum, the digestate from Bio-Wat Sp. z. o. o., Świdnica, Poland, was used. The results showed that released biogas reached 672 mL × g_vs⁻¹, and the yield was 4% higher than in the variant without the SBC. Kinetics study indicated that the biogas production constant rate reached 0.214 d⁻¹ and was 4.4% higher than in the variant without the SBC.