Data-driven patient stratification of UK Biobank cohort suggests five endotypes of multimorbidity.

Multimorbidity generally refers to concurrent occurrence of multiple chronic conditions. These patients are inherently at high risk and often lead a poor quality of life due to delayed treatments. With the emergence of personalized medicine and stratified healthcare, there is a need to stratify patients right at the primary care setting. Here we developed multimorbidity analysis pipeline (MulMorPip), which can stratify patients into multimorbid subgroups or endotypes based on their lifetime disease diagnosis and characterize them based on demographic features and underlying disease-disease interaction networks. By implementing MulMorPip on UK Biobank cohort, we report five distinct molecular subclasses or endotypes of multimorbidity. For each patient, we calculated the existence of broad disease classes defined by Charlson's comorbidity classification using the International Classification of Diseases-10 encoding. We then applied multiple correspondence analysis in 77 524 patients from UK Biobank, who had multimorbidity of more than one disease, which resulted in five multimorbid clusters. We further validated these clusters using machine learning and were able to classify 20% model-blind test set patients with an accuracy of 97% and an average Jaccard similarity of 84%. This was followed by demographic characterization and development of interlinking disease network for each cluster to understand disease-disease interactions. Our identified five endotypes of multimorbidity draw attention to dementia, stroke and paralysis as important drivers of multimorbidity stratification. Inclusion of such patient stratification at the primary care setting can help general practitioners to better observe patients' multiple chronic conditions, their risk stratification and personalization of treatment strategies.

Strain-dependent induction of primary bile acid 7-dehydroxylation by cholic acid.

BACKGROUND: Bile acids (BAs) are steroid-derived molecules with important roles in digestion, the maintenance of host metabolism, and immunomodulation. Primary BAs are synthesized by the host, while secondary BAs are produced by the gut microbiome through transformation of the former. The regulation of microbial production of secondary BAs is not well understood, particularly the production of 7-dehydroxylated BAs, which are the most potent agonists for host BA receptors. The 7-dehydroxylation of cholic acid (CA) is well established and is linked to the expression of a bile acid-inducible (bai) operon responsible for this process. However, little to no 7-dehydroxylation has been reported for other host-derived BAs (e.g., chenodeoxycholic acid, CDCA or ursodeoxycholic acid, UDCA). RESULTS: Here, we demonstrate that the 7-dehydroxylation of CDCA and UDCA by the human isolate Clostridium scindens is induced when CA is present, suggesting that CA-dependent transcriptional regulation is required for substantial 7-dehydroxylation of these primary BAs. This is supported by the finding that UDCA alone does not promote expression of bai genes. CDCA upregulates expression of the bai genes but the expression is greater when CA is present. In contrast, the murine isolate Extibacter muris exhibits a distinct response; CA did not induce significant 7-dehydroxylation of primary BAs, whereas BA 7-dehydroxylation was promoted upon addition of germ-free mouse cecal content in vitro. However, E. muris was found to 7-dehydroxylate in vivo. CONCLUSIONS: The distinct expression responses amongst strains indicate that bai genes are regulated differently. CA promoted bai operon gene expression and the 7-dehydroxylating activity in C. scindens strains. Conversely, the in vitro activity of E. muris was promoted only after the addition of cecal content and the isolate did not alter bai gene expression in response to CA. The accessory gene baiJ was only upregulated in the C. scindens ATCC 35704 strain, implying mechanistic differences amongst isolates. Interestingly, the human-derived C. scindens strains were also capable of 7-dehydroxylating murine bile acids (muricholic acids) to a limited extent. This study shows novel 7-dehydroxylation activity in vitro resulting from the presence of CA and suggests distinct bai gene expression across bacterial species.

Impact of COVID-19 monoclonal antibodies on outcomes of COVID-19 infection in hematopoietic stem cell transplant and chimeric antigen receptor therapy recipients.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) and chimeric antigen receptor T-cell therapy (CAR-T) recipients are at higher risk of serious complications of COVID-19 infection than the general population. Though there is evidence that monoclonal antibodies (MCA) against COVID-19 reduce the risk of death and hospitalization in the general population, data regarding their efficacy in HSCT and CAR-T recipients remains scarce. METHODS: We conducted a retrospective review of HSCT and CAR-T recipients to compare 30-day outcomes between patients who did and did not receive MCA after their first episode of COVID-19 between May 1, 2020 and December 31, 2022. Outcomes were defined as the most severe complication experienced out of the following: 30-day emergency department visit, hospitalization, intensive care unit admission, and death after COVID-19 infection. RESULTS: We identified 166 patients comprised of 53.6% allogeneic HSCT, 35.5% autologous HSCT, and 10.8% CAR-T recipients; 107 had received a COVID-19 vaccine >2 weeks prior to testing positive, and 40 were treated with MCA. After adjusting for age, presence of symptoms at the initial positive test, and COVID-19 vaccination status, patients who did not receive MCA were five times more likely to develop complications after COVID-19 infection (adjusted odds ratio 5.0 [95% CI, 1.9-12.8], p = .001). CONCLUSION: HSCT and CAR-T recipients who received MCA following COVID-19 infection were far less likely to develop COVID-related complications than those who did not receive MCA, regardless of vaccination status. This underscores the potential benefit of developing novel MCA with efficacy against circulating COVID-19 strains.

Plaque features of the middle cerebral artery are associated with periprocedural complications of intracranial angioplasty and stenting.

PURPOSE: The identification of plaque features in the middle cerebral artery (MCA) may help minimize periprocedural complications and select patients suitable for percutaneous transluminal angioplasty and stenting (PTAS). However, relevant research is lacking. METHODS: We retrospectively included patients with symptomatic MCA stenosis who received PTAS. All patients underwent intracranial vessel wall MRI (VWMRI) before surgery. Periprocedural complications (PC) included ischemic and hemorrhagic stroke within 30 days. Stenosis location, MCA shape, plaque eccentricity and distribution, plaque thickness and length, and enhancement ratio were compared between patients with and without PC. RESULTS: Sixty-six patients were included in the study, of which 12.1% (8/66) had PC. Of the eight patients with PC, seven (87.5%) had superior wall plaques. In the non-PC group (n = 58), nine (17%) patients had superior wall plaques. Compared with patients without PC, those with PC had more frequent superior wall plaques (17% vs 87.5%, p < 0.001) and s-shaped MCAs (19% vs 50%, p = 0.071), different stenosis locations (p = 0.012), thicker plaques (1.58 [1.35, 2.00] vs 1.98 [1.73, 2.43], p = 0.038), and less frequent inferior wall plaques (79.2% vs 12.5%, p < 0.001). Multivariate analysis showed that only the presence of superior wall plaques (OR = 41.54 [2.31, 747.54]) was independently associated with PC. CONCLUSION: MCA plaque features were highly correlated with PC in patients with symptomatic MCA stenosis who underwent PTAS.

Middle cerebral artery hypodense dot sign in iatrogenic air embolism.

Air embolism is a rare cause of stroke, usually associated with medical procedures, with gastrointestinal endoscopy rarely implicated. Here, we present a case of a patient who experienced cerebral air embolism post-gastroscopy, presenting with aphasia and right hemiparesis due to left M2 occlusion with spontaneous and complete recovery. CT scan revealed a hypodense defect in the left Sylvian fissure, representing a "hypodense dot sign" suggestive of an air embolism. The hypodense MCA sign, previously described in fat embolism cases, could also indicate air embolism, supporting prompt diagnosis and proper intervention.

Physiological roles of Arabidopsis MCA1 and MCA2 based on their dynamic expression patterns.

Determining the mechanisms by which plants sense and respond to mechanical stimuli is crucial for unraveling the detailed processes by which plants grow and develop. Mechanosensitive (MS) channels, including MCA1 and its paralog MCA2 in Arabidopsis thaliana, may be essential for these processes. Although significant progress has been made in elucidating the physiological roles of MS channels, comprehensive insights into their expression dynamics remain elusive. Here, we summarize recent advancements and new data on the spatiotemporal expression patterns of the MCA1 and MCA2 genes, revealing their involvement in various developmental processes. Then, we describe findings from our study, in which the expression profiles of MCA1 and MCA2 were characterized in different plant organs at various developmental stages through histochemical analyses and semiquantitative RT‒PCR. Our findings revealed that MCA1 and MCA2 are preferentially expressed in young tissues, suggesting their pivotal roles in processes such as cell division, expansion, and mechanosensing. Lastly, we discuss the differential expression patterns observed in reproductive organs and trichomes, hinting at their specialized functions in response to mechanical cues. Overall, this review provides valuable insights into the dynamic expression patterns of MCA1 and MCA2, paving the way for future research on the precise roles of these genes in planta.

Usefulness of STA ultrasonography parameters after STA-MCA bypass in patients with moyamoya disease: A short review.

STA bypass assessment by ultrasonography after bypass surgery in patients with moyamoya disease is minimally invasive and can be performed repeatedly. With STA bypass assessment by ultrasonography, it was shown that in the short term, blood flow that passes through the STA peaks approximately 5 days after the bypass surgery and then gradually decreases over 7 days. In the medium and long terms, it has been shown that the blood flow through the bypass decreases, compared with that during the first postoperative week, and continues for approximately half a year. The ultrasonographic STA parameters can also clearly indicate bypass patency, but there remains some discussion regarding bypass function. Although some reports have tried to show that these parameters are also useful for predicting acute-phase TNEs and predicting the future of bypass function, no studies have yet examined these parameters in detail in relation to the state of cerebral circulation or degree of residual antegrade flow, and additional studies are needed in the future.

STA-MCA Double-Barrel Bypass: A Systematic Review of Technique and Single-Arm Meta-Analysis of Outcomes.

INTRODUCTION: Conventionally, one branch of the superficial temporal artery (STA) is utilized to revascularize the middle cerebral artery (MCA). However, there is the possibility of utilizing both branches of the STA when performing the bypass, characterizing the double-barrel (DB) STA-MCA bypass. Notably, a lack of studies evaluating this technique led the authors to conduct a systematic review and single-arm meta-analysis. METHODS: PubMed, Embase and Web of Science were searched systematically for publications of DB-STA-MCA bypass on November 1st, 2023. The findings were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Case reports were not included for statistical analysis purposes. RESULTS: The review included 408 patients and 534 bypasses from 34 studies. The main etiology was Moyamoya disease (64.6%), followed by cerebral ischemia (22.2%) and aneurysms (12.5%). The median of the mean follow-ups of each study was 12.8 months (range 1.5-87.9). The postoperative patency was 100%. The follow-up patency was 98% (95% CI: 96%-100%; I2 = 0%). The procedure-related mortality was 0% (95% CI: 0%-1%; I2 = 0%). Aneurysms obtained 87% (95% CI: 72%-100%; I2 = 4%) of good clinical outcomes, while Moyamoya disease yielded a rate of 70% (95% CI: 10%-100%; I2 = 97%). Ischemic complications occurred at a rate of 6% (95% CI: 2%-11%; I2 = 36%), while hemorrhagic occurred at 6% (95% CI: 1%-11%; I2 = 56%). Hyperperfusion syndrome rate was calculated as 18% (7%-30%; I2 = 55%) for Moyamoya disease. CONCLUSIONS: The procedure appears to be safe, with excellent patency rates. The clinical efficacy for ischemic and Moyamoya diseases warrants further standardized robust investigation with a broader number of patients, and aneurysm studies are required to enhance sample sizes. The main complication for the Moyamoya subgroup is hyperperfusion syndrome.

Preoperative collateralization depending on posterior components in the prediction of transient neurological events in moyamoya disease.

Changes in local cerebral blood flow (CBF) are a major cause of transient neurological events (TNEs) after revascularization for moyamoya disease (MMD); however, the influence of preoperative collateral pathway development on TNEs has not yet been investigated. This study included 28 hemispheres from 28 consecutive patients with MMD who underwent surgical revascularization, including a superficial temporal artery (STA) to middle cerebral artery (MCA) bypass, between January 2014 and March 2022. The collateralization pathways included the anterior communicating artery (AcomA) collaterals, posterior communicating artery (PcomA) collaterals, transdural collaterals, posterior pericallosal anastomosis, lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis. These collateral pathways were analyzed to identify predictive factors significantly associated with TNEs. TNEs were observed in 11 (39.3%) hemispheres. The development of posterior pericallosal anastomosis and choroidal anastomosis was a significant independent predictor of the occurrence of TNEs after bypass surgery for MMD (P = 0.01, OR 26.9, 95% CI 1.50-480.0; P = 0.002, OR 47.6, 95% CI 2.65-856.6). The development of choroidal and posterior pericallosal anastomosis could be reliable preoperative predictors of TNEs after bypass surgery for MMD. Our results provide useful information for future studies aimed at clarifying the mechanisms underlying TNEs.

Giant unruptured middle cerebral artery aneurysm revealed by intracranial hypertension: is a systematic decompressive hemicraniotomy mandatory?

Our study aimed to evaluate the postoperative outcome of patients with unruptured giant middle cerebral artery (MCA) aneurysm revealed by intracranial hypertension associated to midline brain shift. From 2012 to 2022, among the 954 patients treated by a microsurgical procedure for an intracranial aneurysm, our study included 9 consecutive patients with giant MCA aneurysm associated to intracranial hypertension with a midline brain shift. Deep hypothermic circulatory flow reduction (DHCFR) with vascular reconstruction was performed in 4 patients and cerebral revascularization with aneurysm trapping was the therapeutic strategy in 5 patients. Early (< 7 days) and long term clinical and radiological monitoring was done. Good functional outcome was considered as mRS score ≤ 2 at 3 months. The mean age at treatment was 44 yo (ranged from 17 to 70 yo). The mean maximal diameter of the aneurysm was 49 mm (ranged from 33 to 70 mm). The mean midline brain shift was 8.6 mm (ranged from 5 to 13 mm). Distal MCA territory hypoperfusion was noted in 6 patients. Diffuse postoperative cerebral edema occurred in the 9 patients with a mean delay of 59 h and conducted to a postoperative neurological deterioration in 7 of them. Postoperative death was noted in 3 patients. Among the 6 survivors, early postoperative decompressive hemicraniotomy was required in 4 patients. Good functional outcome was noted in 4 patients. Complete aneurysm occlusion was noted in each patient at last follow-up. We suggest to discuss a systematic decompressive hemicraniotomy at the end of the surgical procedure and/or a partial temporal lobe resection at its beginning to reduce the consequences of the edema reaction and to improve the postoperative outcome of this specific subgroup of patients. A better intraoperative assessment of the blood flow might also reduce the occurrence of the reperfusion syndrome.

Regeneration of tunic cuticle is suppressed in edible ascidian Halocynthia roretzi contracting soft tunic syndrome.

Soft tunic syndrome is an infectious disease caused by the flagellate Azumiobodo hoyamushi, which severely damages the aquaculture of the edible ascidian Halocynthia roretzi. Tunic is a cellulosic extracellular matrix entirely covering the body in ascidians and other tunicates, and its dense cuticle layer covers the tunic surface as a physical barrier against microorganisms. When the tunic of intact H. roretzi individuals was cut into strips, electron-dense fibers (DFs) appeared on the cut surface of the tunic matrix and aggregated to regenerate a new cuticular layer in seawater within a few days. DF formation was partially or completely inhibited in individuals with soft tunic syndrome, and DF formation was also inhibited by the presence of some proteases, indicating the involvement of proteolysis in the process of tunic softening as well as cuticle regeneration. Using pure cultures of the causative flagellate A. hoyamushi, the expression of protease genes and secretion of some proteases were confirmed by RNA-seq analysis and a 4-methylcoumaryl-7-amide substrate assay. Some of these proteases may degrade proteins in the tunic matrix. These findings suggest that the proteases of A. hoyamushi is the key to understanding the mechanisms of cuticular regeneration inhibition and tunic softening.

Case report: thrombectomy for left internal carotid artery occlusion with ipsilateral dual accessory middle cerebral arteries.

Accessory middle cerebral arteries (AMCAs) are found in 0.3-4.0% of cases, and ipsilateral dual AMCAs are rare. A seventy-three-year-old man presented with right hemiplegia and total aphasia. Magnetic resonance angiography showed left carotid artery occlusion. We infused him with tissue plasminogen activator. Digital subtraction angiogram showed revascularization of the left internal carotid artery. However, the left proximal anterior cerebral artery was occluded. We performed mechanical thrombectomy and achieved partial reperfusion. CT angiography on the tenth day showed ipsilateral dual AMCAs. Due to middle cerebral artery anomalies, we performed mechanical thrombectomy using contact aspiration which is safer than other techniques.

A novel intraoperative "Faucet" technique for assessing patency of superficial temporal artery to middle cerebral artery bypass and for prevention of microemboli.

PURPOSE: This technical note introduces the novel faucet technique, which enables neurosurgeons to evaluate the patency of a bypass during superficial temporal artery-middle cerebral artery bypass surgery. The technique is particularly useful when there is a lack of equipment such as micro-Doppler or indocyanine green in the operating rooms. This is often the case in Central Asian countries. METHODS: The faucet technique involves carefully examining the graft by gently opening a valve, comparable to a faucet, to observe the blood flow through the bypassed vessel. Overall, 36 procedures underwent the faucet technique for assessing the superficial temporal artery-middle cerebral artery bypass patency. RESULTS: The results indicate that the bypass remained patent in all cases, as confirmed through the intraoperative faucet technique, postoperative magnetic resonance angiography, or cerebral angiography. CONCLUSION: By visually inspecting the blood flow through the faucet technique, surgeons can confirm the effectiveness of the graft and ensure that the bypass remains unobstructed during the surgery.

Hardware Development and Evaluation of Multihop Cluster-Based Agricultural IoT Based on Bluetooth Low-Energy and LoRa Communication Technologies.

In this paper, we present the development and evaluation of a contextually relevant, cost-effective, multihop cluster-based agricultural Internet of Things (MCA-IoT) network. This network utilizes commercial off-the-shelf (COTS) Bluetooth Low-Energy (BLE) and LoRa communication technologies, along with the Raspberry Pi 3 Model B+ (RPi 3 B+), to address the challenges of climate change-induced global food insecurity in smart farming applications. Employing the lean engineering design approach, we initially implemented a centralized cluster-based agricultural IoT (CA-IoT) hardware testbed incorporating BLE, RPi 3 B+, STEMMA soil moisture sensors, UM25 m, and LoPy low-power Wi-Fi modules. This system was subsequently adapted and refined to assess the performance of the MCA-IoT network. This study offers a comprehensive reference on the novel, location-independent MCA-IoT technology, including detailed design and deployment insights for the agricultural IoT (Agri-IoT) community. The proposed solution demonstrated favorable performance in indoor and outdoor environments, particularly in water-stressed regions of Northern Ghana. Performance evaluations revealed that the MCA-IoT technology is easy to deploy and manage by users with limited expertise, is location-independent, robust, energy-efficient for battery operation, and scalable in terms of task and size, thereby providing a versatile range of measurements for future applications. Our results further demonstrated that the most effective approach to utilizing existing IoT-based communication technologies within a typical farming context in sub-Saharan Africa is to integrate them.

Deoxyxylulose 5-Phosphate Synthase Does Not Play a Major Role in Regulating the Methylerythritol 4-Phosphate Pathway in Poplar.

The plastidic 2-C-methylerythritol 4-phosphate (MEP) pathway supplies the precursors of a large variety of essential plant isoprenoids, but its regulation is still not well understood. Using metabolic control analysis (MCA), we examined the first enzyme of this pathway, 1-deoxyxylulose 5-phosphate synthase (DXS), in multiple grey poplar (Populus × canescens) lines modified in their DXS activity. Single leaves were dynamically labeled with 13CO2 in an illuminated, climate-controlled gas exchange cuvette coupled to a proton transfer reaction mass spectrometer, and the carbon flux through the MEP pathway was calculated. Carbon was rapidly assimilated into MEP pathway intermediates and labeled both the isoprene released and the IDP+DMADP pool by up to 90%. DXS activity was increased by 25% in lines overexpressing the DXS gene and reduced by 50% in RNA interference lines, while the carbon flux in the MEP pathway was 25-35% greater in overexpressing lines and unchanged in RNA interference lines. Isoprene emission was also not altered in these different genetic backgrounds. By correlating absolute flux to DXS activity under different conditions of light and temperature, the flux control coefficient was found to be low. Among isoprenoid end products, isoprene itself was unchanged in DXS transgenic lines, but the levels of the chlorophylls and most carotenoids measured were 20-30% less in RNA interference lines than in overexpression lines. Our data thus demonstrate that DXS in the isoprene-emitting grey poplar plays only a minor part in controlling flux through the MEP pathway.

A Novel Intumescent MCA-Modified Sodium Silicate/Acrylic Flame-Retardant Coating to Improve the Flame Retardancy of Wood.

The incompatibility between inorganic flame retardants and organic acrylic coatings represents a significant challenge that requires resolution. This work selected environmentally friendly organic aqueous acrylic coatings as the substrate, sodium silicate hydrate as the inorganic flame retardant, and melamine cyanurate (MCA) as the flame-retardant modifier and the flame-retardant co-modifier, with the objective of improving the dispersion and flame-retardant properties of sodium silicate hydrate in the aqueous acrylic coatings. Subsequently, the sodium silicate/MCA/waterborne acrylic acid flame-retardant coating was prepared. The flame-retardant treatment was then applied to poplar veneer in order to create a flame-retardant poplar veneer. The dispersion of the flame-retardant coating was characterized by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDX), and X-ray diffractometry (XRD). Furthermore, the flame-retardant properties of the flame-retardant poplar veneer were analyzed by thermogravimetry (TG), limiting oxygen index (LOI), and cone calorimeter. The results demonstrated that the MCA-modified sodium silicate flame retardant was well dispersed in aqueous acrylic coatings. The results of the flame-retardant properties of the poplar veneer indicated that the ignition time of the 9% flame retardant-treated poplar veneer was increased by 122.7%, the limiting oxygen index value was increased by 43.0%, and the peak heat release rate (pHRR), the peak total heat release rate (pTHR), and the peak mass loss rate were decreased by 19.9%, 10.8%, and 27.2%, respectively, in comparison to the non-flame retardant-treated poplar veneer. Furthermore, the residual char mass increased by 14.4%, and the residual char exhibited enhanced thickness, density, and regularity. The results demonstrated that MCA was an effective promoter of sodium silicate dispersion in acrylic coatings. Furthermore, the sodium silicate/MCA/waterborne acrylic flame-retardant coating significantly enhance the flame retardancy of wood, and its flame retardant mechanism was consistent with the synergistic silicone-nitrogen expansion flame-retardant mechanism. This work presents a novel approach to enhancing the dispersion of inorganic flame retardants in organic coatings, offering a valuable contribution to the advancement of research and application in the domains of innovative flame retardant coatings and flame retardant wood.

Omics data for sampling thermodynamically feasible kinetic models.

Kinetic models are key to understanding and predicting the dynamic behaviour of metabolic systems. Traditional models require kinetic parameters which are not always available and are often estimated in vitro. Ensemble models overcome this challenge by sampling thermodynamically feasible models around a measured reference point. However, it is unclear if the convenient distributions used to generate the ensemble produce a natural distribution of model parameters and hence if the model predictions are reasonable. In this paper, we produced a detailed kinetic model for the central carbon metabolism of Escherichia coli. The model consists of 82 reactions (including 13 reactions with allosteric regulation) and 79 metabolites. To sample the model, we used metabolomic and fluxomic data from a single steady-state time point for E. coli K-12 MG1655 growing on glucose minimal M9 medium (average sampling time for 1000 models: 11.21 ± 0.14 min). Afterwards, in order to examine whether our sampled models are biologically sound, we calculated Km, Vmax and kcat for the reactions and compared them to previously published values. Finally, we used metabolic control analysis to identify enzymes with high control over the fluxes in the central carbon metabolism. Our analyses demonstrate that our platform samples thermodynamically feasible kinetic models, which are in agreement with previously published experimental results and can be used to investigate metabolic control patterns within cells. This renders it a valuable tool for the study of cellular metabolism and the design of metabolic pathways.

Successful mechanical thrombectomy in acute bilateral M1 middle cerebral artery occlusion: a case report and literature review.

BACKGROUND: Acute bilateral occlusion of the middle cerebral artery (MCA) is a very rare condition, and most cases are accompanied by a poor prognosis. However, mechanical thrombectomy (MT) for bilateral MCA is challenging. Here, we report a case of acute unilateral MCA occlusion with sequential acute occlusion of the bilateral MCA during intravenous thrombolysis (IVT). We urgently performed bilateral MT of the MCA and effective recanalization. CASE PRESENTATION: The patient is a 73-year-old man who complained of a sudden adverse influence on speech and an inability to move his left limb for 2 h. He had a history of paroxysmal atrial fibrillation, but had never used any anticoagulants before. Head and neck computed tomography angiography (CTA) showed embolism in the right M1 MCA. During intravenous alteplase thrombolytic therapy, the patient suddenly became unconscious. Cerebral angiography showed occlusion of the M1 segment of the bilateral MCA in the patients. MT of the bilateral MCA was performed using a combination of a stent retriever and an aspiration catheter with mTici 3 revascularization. On the second day, the patient became conscious, although he had remaining symptoms of speech insufficiency and weakness of the left limb. The mRS score was 2 90 days after the operation. CONCLUSIONS: Acute bilateral occlusion of the M1 segment of the MCA is extremely rare and is accompanied by high morbidity and high mortality. Intravenous alteplase thrombolysis can increase the risk of atrial thrombus shedding in patients with atrial fibrillation, so patients with acute bilateral MCA occlusion in the M1 segment chose direct MT or bridging therapy, which remains controversial, and the sequence of MT remains to be discussed. Nevertheless, early endovascular treatment can decrease the morbidity and mortality of such patients.

Side-to-side duodeno-ileal magnetic compression anastomosis: design and feasibility of a novel device in a porcine model.

BACKGROUND: Minimally invasive metabolic/bariatric surgery (MBS) may be further advanced by magnetic compression anastomosis (MCA) technology. The study aimed to develop a magnet sized to create a patent duodeno-ileostomy (DI) and verify its effectiveness in a porcine model. METHODS: Developmental study phase: magnets with 4 different flange-offset dimensions were tested to identify a design that would successfully form a compression anastomosis. Verification phase: evaluation of the selected design's efficacy. In each 6-week phase (4 pigs/phase), one magnet was inserted laparoscopically in the jejunum, one placed gastroscopically in the duodenum. Magnets were aligned, gradually fused, formed an anastomosis, and then detached and were expelled. At necropsy, MCA sites and sutured enterotomy sites were collected and compared. RESULTS: Developmental phase: the linear BC42 magnet with a 2.3-mm flange offset design was selected. Verification phase: in 4 swine magnets were mated at the target location, confirmed radiographically. Mean time to magnet detachment 16.0 days (12-22), to expulsion 24.5 days (17-33). MCA was achieved in all animals at time of sacrifice. Animals gained a mean 9.5 kg (3.9-11.8). Specimens revealed patent anastomoses of ≥ 20 mm with smooth mucosa and minimal inflammation and fibrosis compared to sutured enterotomies. One pig underwent corrective surgery for a mesenteric hernia without sequelae. CONCLUSION: In a large-animal model, gross and histopathologic examination confirmed that the linear MCA device created a patent, well-vascularized, duodeno-ileal anastomosis. The novel MCA device may be appropriate for use in human MBS procedures.

Transition in the ages at key reproductive events and its determinants in India: evidence from NFHS 1992-93 to 2019-21.

INTRODUCTION: Reproductive health events have changed fertility and family planning needs, depicting the changing life patterns of women and the population to which they belong. Understanding the pattern at which these events occur helps in understanding the fertility pattern, family formation and the idea about health essential needs for women. This paper attempts to see the variation in reproductive events (first cohabitation, first sex and first birth) over three decades and also to see potential contributing factors among the reproductive age group of women using secondary data from Data Source: All rounds of the National Family Health Survey (1992-93 to 2019-2021) have been utilized. METHODS AND RESULTS: Cox Proportional Hazard Model illustrates that all regions have initiated their first birth later than women who belong to the east region similar pattern has been obtained for first cohabitation and first sex except for the central region. Multiple Classification Analysis (MCA) depicts the increasing pattern in the predicted mean age at first cohabitation, sex and birth for all demographic characteristics; the highest increment was found in SC women, Uneducated women and Muslim women. Kaplan Meier Curve demonstrates that women with no education, primary or secondary education are shifting towards higher educated women. Most importantly, the results of the multivariate decomposition analysis (MDA) revealed that education played the largest contribution among the compositional factors in the overall increase in mean ages at key reproductive events. CONCLUSIONS: Though reproductive health has long been essential in women's lives, they are still very confined to specific domains. Over time the government has formulated several proper legislative measures relating to various domains of reproductive events. However, given that the large size and heterogeneity in social and cultural norms result in changing ideas and choices regarding the initiation of reproductive events, national policy formulation needs to be improved or amended.