Modeling Spinal Muscular Atrophy in Drosophila

Spinal Muscular Atrophy (SMA), a recessive hereditary neurodegenerative disease in humans, has been linked to mutations in the survival motor neuron (SMN) gene. SMA patients display early onset lethality coupled with motor neuron loss and skeletal muscle atrophy. We used Drosophila, which encodes a single SMN ortholog, survival motor neuron (Smn), to model SMA, since reduction of Smn function leads to defects that mimic the SMA pathology in humans. Here we show that a normal neuromuscular junction (NMJ) structure depends on SMN expression and that SMN concentrates in the post-synaptic NMJ regions. We conducted a screen for genetic modifiers of an Smn phenotype using the Exelixis collection of transposon-induced mutations, which affects approximately 50% of the Drosophila genome. This screen resulted in the recovery of 27 modifiers, thereby expanding the genetic circuitry of Smn to include several genes not previously known to be associated with this locus. Among the identified modifiers was wishful thinking (wit), a type II BMP receptor, which was shown to alter the Smn NMJ phenotype. Further characterization of two additional members of the BMP signaling pathway, Mothers against dpp (Mad) and Daughters against dpp (Dad), also modify the Smn NMJ phenotype. The NMJ defects caused by loss of Smn function can be ameliorated by increasing BMP signals, suggesting that increased BMP activity in SMA patients may help to alleviate symptoms of the disease. These results confirm that our genetic approach is likely to identify bona fide modulators of SMN activity, especially regarding its role at the neuromuscular junction, and as a consequence, may identify putative SMA therapeutic targets

Perspective directions of blockchain technology usage in digital marketing

The article outlines the key directions for usage of the blockchain technology in digital marketing, describes the new business models of digital enterprises. The article characterizes the dynamics of changes in IT budgets of new business models of digital enterprises. Authors define the relationship of new business models in the digital economy. Authors suggest classification of enterprises based on approaches to the use of operational efficiency and customer experience. The directions ofdevelopment ofdigital enterprises are determined. Conclusions made on the structural changes ofdigital marketing

Structural and functional units of parenchyma of lymph nodes of dromedaries (Camelus dromedarius)

This article analyzes patterns of structural and functional organization of the parenchyma of different groups of lymph nodes, structural features of their connective tissue frame and lymphatic sinuses. We studied superficial and deep somatic (Limphonodi mandibulares, L. cervicales superficiales, L. axillares proprii, L. poplitei), somatovisceral (L. retropharyngei mediales, L. iliaci mediales), visceral (L. mediastinales caudales, L. jejunales) features of mature male dromedaries (Camelus dromedarius Linnaeus, 1758). We used a complex of traditional macroscopic and histological techniques, and also immunohistochemical staining of lymph node sections for identifying the features of localization of T- and B-lymphocyte populations in the parenchyma of the nodes. We found that the parenchyma of camels’ lymph nodes is characterized by a spongy type structure in the form of a complex of partly concrescent round-oval fragments of lymphoid tissue, surrounded by large lymphatic spaces (sinuses). The connective tissue frame of the lymph nodes is represented by a two-layer (connective tissue-muscular) capsule and two types of trabeculae: two-layered (connective-muscular, type I), which contain blood and lymphatic vessels, as well as lymphatic cysternas, and single-layered, formed only by a smooth muscular system (type II). Intranodal lymphatic sinuses are subdivided into subcapsular, peritrabecular and medullary sinuses. The subcapsular sinuses and sinuses related to trabeculae of type I and their branching is the most developed. At the tissue level, the lymph node parenchyma has a clearly manifested lobular structure. Lymphoid lobules in the lymph node parenchyma are positioned diffusely (mosaically) and consist of four main cellular zones: transit and cell-cell interaction (analogous to the cortical plateau), clonal proliferation of T- and, respectively, B-lymphocytes (deep cortex units, lymphatic nodules), accumulation of plasmocytes and synthesis of antibodies (brain cords). The lymphoid lobes (compartments) of the lymph nodes parenchyma are bipolar, their tops formed by the zones of transit and cell-cell interaction, and also by the zones of proliferation of B lymphocytes, and the bases by a complex of brain cords (zone of accumulation of plasmocytes and synthesis of antibodies). The zone of T-lymphocytes proliferation is in intermediate position and underlies the subunits of the parenchyma. The tops of the lymphoid lobes are located along the sinuses of the trabeculae of type I and the bases along the sinuses of the trabeculae of type II, which form the efferent lymphatic vessels. The maximum relative capacity of all studied lymph nodes was typical for zones of plasmocyte accumulation and synthesis of antibodies (19–27%), the minimum capacity was typical for transit and cell-cell interaction zones (3–8%). The relative capacity of zones of clonal proliferation of T- and B-lymphocytes in most lymph nodes was 1.5–3.0 times less than that of the zone of plasmocyte accumulation and antibody formation and was, respectively, 8–16% and 9–18%. The study showed that the structure of the lymph nodes parenchyma of dromedaries is not absolutely unique. As in other mammal species, it is subdivided into specialized cell zones which are connected in lymphoid lobules. Specific features of parenchyma structure include: diffuse (mosaic) location of lymphoid lobules; absence of signs of regulated localization of lymphoid lobules relative to the capsule and the sinus bordering the nodes

Prenatal morphogenesis of compartments of the parenchyma of the lymph nodes of domestic cattle (Bos taurus)

The article analyzes the regularities of the formation and development of the lymphoid lobules of the parenchyma of the somatic (Limphonodi cervicales superficiales) and visceral (L. jejunales) lymph nodes in domestic cattle in the fetal period of ontogenesis. We used routine histological techniques and author's modification of the impregnation of total median sections with silver nitrate. Visualization of various zones of lymphoid lobules was carried out taking into account the specific for different cell zones architectonics of reticular fibers. It has been established that signs of morphological heterogeneity of parenchyma of lymph nodes are first found in three month-old fetuses, which is associated with the concentration of lymphoid tissue along the marginal sinus. Separation of lymphoid lobules and their structural and functional differentiation are first detected in five month fetuses. In the lymphoid lobules of five month-old fetuses all structural and functional cell zones are observable, among which the regions of clonal proliferation of T and B lymphocytes are the least developed, and regions of the transit corridors for lymphocytes migrating medullary and the cords (zone of potential accumulation of plasmocytes and antibody formation) are the most developed. Structural and functional transformations of compartments in the prenatal period of ontogenesis are accompanied by a predominantly moderate increase of the relative volume of specialized T- and B-dependent zones of lobules, against a background of a gradual decrease of the volume of transit corridors for lymphocytes migrating and zone of potential accumulation of plasmocytes and antibody formation. Due to the small volume and relatively low rates of development of the lymphocytes clonal proliferation zones, the quantitative ratios of the cellular zones in lymphoid lobules of the lymph nodes of domestic cattle in prenatal ontogenesis remain relatively stable, while maintaining the maximum indices of the development of transit corridors for lymphocytes migration and medullary cords. Among the zones of lymphocytes clonal proliferation throughout the fetal period, T-dependent zones predominate, the relative volume of which is 5.0–7.5 times greater than the volume of B-dependent zones. Lymphoid lobules in the lymph nodes of the domestic cattle fetuses of all age groups are arranged along the marginal sinus in one row and have a polar structure due to the formation of lymph nodes at one pole of the lobules in the interfollicular zone. In the visceral lymph nodes (L. jejunum) of 8–9 month-old fetuses, individual lymph nodes can form in paracortical strands, on the border with the interfollicular zone

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien–Dindo classification system. Results: A total of 3288 patients were included in the analysis, of whom 301 (9·2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4–7) and 7 (6–8) days respectively (P < 0·001). There were no significant differences in rates of readmission between these groups (6·6 versus 8·0 per cent; P = 0·499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0·90, 95 per cent c.i. 0·55 to 1·46; P = 0·659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34·7 versus 39·5 per cent; major 3·3 versus 3·4 per cent; P = 0·110). Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien-Dindo classification system. Results A total of 3288 patients were included in the analysis, of whom 301 (9 center dot 2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4-7) and 7 (6-8) days respectively (P < 0 center dot 001). There were no significant differences in rates of readmission between these groups (6 center dot 6 versus 8 center dot 0 per cent; P = 0 center dot 499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0 center dot 90, 95 per cent c.i. 0 center dot 55 to 1 center dot 46; P = 0 center dot 659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34 center dot 7 versus 39 center dot 5 per cent; major 3 center dot 3 versus 3 center dot 4 per cent; P = 0 center dot 110). Conclusion Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients

Timing of nasogastric tube insertion and the risk of postoperative pneumonia: an international, prospective cohort study

Aim: Aspiration is a common cause of pneumonia in patients with postoperative ileus. Insertion of a nasogastric tube (NGT) is often performed, but this can be distressing. The aim of this study was to determine whether the timing of NGT insertion after surgery (before versus after vomiting) was associated with reduced rates of pneumonia in patients undergoing elective colorectal surgery. Method: This was a preplanned secondary analysis of a multicentre, prospective cohort study. Patients undergoing elective colorectal surgery between January 2018 and April 2018 were eligible. Those receiving a NGT were divided into three groups, based on the timing of the insertion: routine NGT (inserted at the time of surgery), prophylactic NGT (inserted after surgery but before vomiting) and reactive NGT (inserted after surgery and after vomiting). The primary outcome was the development of pneumonia within 30 days of surgery, which was compared between the prophylactic and reactive NGT groups using multivariable regression analysis. Results: A total of 4715 patients were included in the analysis and 1536 (32.6%) received a NGT. These were classified as routine in 926 (60.3%), reactive in 461 (30.0%) and prophylactic in 149 (9.7%). Two hundred patients (4.2%) developed pneumonia (no NGT 2.7%; routine NGT 5.2%; reactive NGT 10.6%; prophylactic NGT 11.4%). After adjustment for confounding factors, no significant difference in pneumonia rates was detected between the prophylactic and reactive NGT groups (odds ratio 1.03, 95% CI 0.56–1.87, P = 0.932). Conclusion: In patients who required the insertion of a NGT after surgery, prophylactic insertion was not associated with fewer cases of pneumonia within 30 days of surgery compared with reactive insertion