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Analysis of maturation dynamics and oocyte nuclear quality after rescue-IVM and semi-automated vitrification.

STUDY QUESTION: What is the optimal stage (immature vs mature) and most efficient vitrification technique (semi-automated vs manual) to ensure the safety of the rescue-IVM (r-IVM) procedure for oocyte cryopreservation? SUMMARY ANSWER: Human oocytes should be cryopreserved after r-IVM at the mature stage (r-MII oocytes) by semi-automated or manual vitrification. WHAT IS KNOWN ALREADY: r-IVM of immature oocytes may increase the number of oocytes cryopreserved for fertility preservation. However, the best stage and vitrification system (semi-automated or manual) for cryopreserving oocytes with

Nanomolar vanillin, an e-cigarette flavorant, appears to disrupt pluripotency and promote endodermal differentiation in human embryonic stem cells via TRPV4 activation.

STUDY QUESTION: Does vanillin, at concentrations relevant to maternal exposures during vaping, disrupt gastrulation-related processes in hum … ular calcium upon nanomolar-to-micromolar vanillin exposure, as detected by the Fluo-8 calcium dye. Time-lapse imaging and quantitative analysis indicated that micromolar vanillin impaired colony expansion, induced colony detachment, and increased cell death over 72 h, while concurrently reducing mitochondrial reductase activity in the MTT assay. At nanomolar concen …

Automation in the IVF laboratory in 2026: four technology domains, an asymmetric evidence base, and the case for parallel development with clinician-side automation.

BACKGROUND: Operator-dependent laboratory tasks-embryo selection, vitrification and warming, and intracytoplasmic sperm injection (ICSI)-hav … deep-learning selection over standard morphology in clinical pregnancy, and the Cochrane review of time-lapse imaging found no evidence of differences in live birth or clinical pregnancy. The realistic value proposition is workflow standardization rather than improved clinical outcome. (ii) Closed semi-automated vitrification (Gavi) achieves clinical and survival o …

Динамическая съемка миелинской патологии в физиологически сохранившихся человеческих мозговых тканях с использованием третьей гармонической микроскопии.

Известно, что миелиновая патология играет центральную роль в таких расстройствах, как, в частности, множественный склероз (MS). Несмотря на это, патологические механизмы, лежащие в основе этих условий, часто трудно разгадать. Обычные методы, такие, как иммуноистохимия или подходы, основанные на красителях, не обеспечивают временной характеристики патофизиологических отклонений, вызывающих миелиновые изменения в образцах человека. Здесь, чтобы обойти эту обочину, мы представляем подход миелина к изображениям без ярлыков с живыми клетками, используя недавние достижения в нелинейной гармонической

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… This approach facilitates 4D data acquisition through time-lapse imaging of 3D scans. Schematic overview of the THG microscopy setup. …

Exploring Healthcare Continuity in Pediatric-Onset Multiple Sclerosis in the United States.

OBJECTIVE: Little is known about shifting from pediatric to adult-focused multiple sclerosis (MS) care. This study aims to explore transition of care and follow-up in the US pediatric-onset MS (POMS) population. METHODS: Surveys were distributed to 10 sites in the US Network of Pediatric MS Centers (US NPMSC) about transition-of-care practices. A cohort of POMS/clinically isolated syndrome (CIS) at 12 US NPMSC sites was analyzed. The primary comparison was between < 18 and ≥ 18-years of age. The primary outcome was 1- and 2-year lapse in last follow-up visit, measured from last recorded datab

CXCL12/CXCR4 axis supports mitochondrial trafficking in tumor myeloma microenvironment.

Mesenchymal stromal cells (MSCs) within the protective microenvironment of multiple myeloma (MM) promote tumor growth, confer chemoresistance and support metabolic needs of plasma cells (PCs) even transferring mitochondria. In this scenario, heterocellular communication and dysregulation of critical signaling axes are among the major contributors to progression and treatment failure. Here, we report that myeloma MSCs have decreased reliance on mitochondrial metabolism as compared to healthy MSCs and increased tendency to deliver mitochondria to MM cells, suggesting that this intercellular exch

HDAC Inhibition Induces PD-L1 Expression in a Novel Anaplastic Thyroid Cancer Cell Line.

While papillary thyroid cancer (PTC) has largely favorable prognosis, anaplastic thyroid cancer (ATC) is a rare but extremely aggressive malignancy with grim clinical outcome. Even though new therapeutic options are emerging for ATC, additional preclinical models and novel combinations are needed for specific subsets of patients. We established a novel cell line (PF49) from the malignant pleural effusion of a 68-year-old male patient with ATC that rapidly transformed from a BRAF and TERT promoter mutant PTC. PF49 cells demonstrated a robust migratory activity in vitro and strong invasive capac

Dental extraction following zoledronate, induces osteonecrosis in rat's jaw.

Sarcoptic mange is a parasitic contagious disease that can lead to significant declines in wildlife populations. To identify the most used methods for diagnosing mange in free-ranging wildlife species, a systematic review was conducted across multiple databases: Scopus, PubMed, Web of Science, ProQuest Central and CABI. Citation screening was performed using the web-based platform, Covidence. A customized data extraction form, developed by the authors, was used to collect relevant information. This information was later exported and analyzed using Microsoft Excel. The objectives of this system

Гастродин поощряет миелиогенез CNS и смягчает демиелионирующее повреждение путем активации сигнала PI3K/AKT/mTOR.

Демиелинция является общей особенностью многочисленных неврологических расстройств, включая множественный склероз и лейкодистрофию. Хотя миелин может быть регенерирован самопроизвольно после травмы, этот процесс зачастую является неадекватным, что может привести к нейродегенерации и обострению неврологической дисфункции. Ряд наркотиков, направленных на содействие дифференциации клеток-прекурсоров олигодендроцитов (ОПК), привели к неудовлетворительным клиническим последствиям. В одном из недавних исследований стратегия дифференциации в пользу ОПС была переориентирована на укрепление миелиногене

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… Time-lapse imaging showed the dynamic development of a single representative OL from 3 dpf to 7 dpf, and revealed that myelin fragments were more abundant formed by the gastrodin-treated OL (Fig.  2e ). … e Time-lapse imaging of myelin sheath development of a single OL from 3 dpf to 7 dpf. f Representative images showing myelin sheaths formed by a single OL at 7 dpf and quantification of myelin sheath number per OL ( n  = 42–60 OLs). …

Enumeration, functional responses and cytotoxic capacity of MAIT cells in newly diagnosed and relapsed multiple myeloma.

Mucosal-associated invariant T (MAIT) cells are T cells that recognise vitamin-B derivative Ag presented by the MHC-related-protein 1 (MR1) antigen-presenting molecule. While MAIT cells are highly abundant in humans, their role in tumour immunity remains unknown. Here we have analysed the frequency and function of MAIT cells in multiple myeloma (MM) patients. We show that MAIT cell frequency in blood is reduced compared to healthy adult donors, but comparable to elderly healthy control donors. Furthermore, there was no evidence that MAIT cells accumulated at the disease site (bone marrow) of t

An Integrated Health-System Specialty Pharmacy Model for Coordinating Transitions of Care: Specialty Medication Challenges and Specialty Pharmacist Opportunities.

Adherence and persistence to specialty medications are necessary to achieve successful outcomes of costly therapies. The increasing use of specialty medications has exposed several unique barriers to certain specialty treatments' continuation. Integrated specialty pharmacy teams facilitate transitions in sites of care, between different provider types, among prescribed specialty medications, and during financial coverage changes. We review obstacles encountered within these types of transitions and the role of the specialty pharmacist in overcoming these obstacles. Case examples for each type

Growth inhibition of head and neck squamous cell carcinoma cells by sgRNA targeting the cyclin D1 mRNA based on TRUE gene silencing.

Head and neck squamous cell carcinoma (HNSCC) exhibits increased expression of cyclin D1 (CCND1). Previous studies have shown a correlation between poor prognosis of HNSCC and cyclin D1 overexpression. tRNase ZL-utilizing efficacious gene silencing (TRUE gene silencing) is one of the RNA-mediated gene expression control technologies that have therapeutic potential. This technology is based on a unique enzymatic property of mammalian tRNase ZL, which is that it can cleave any target RNA at any desired site by recognizing a pre-tRNA-like complex formed between the target RNA and an artificial sm

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… The results of 3D analysis of imaging and time-lapse imaging revealed that a large accumulation of sgRNA-Alexa568 was taken up in HSC-3 cells at 6 h after treatment of sgRNA and located in the perinuclear compartment ( Video S1 , S2 and Methods S1 ). … From time-lapse imaging analysis, it was apparent that apoptosis was induced in a subset of the HSC-3 cells which had taken up sgH5-Alexa568 ( Video S2 and Methods S1 ). …

Подстегнутая стрессом связь с нанотрубкой в глиальных клетках CNS: последствия провокационного демиэлирования и отказа в ремонте.

Множественные склерозы и связанные с ними воспалительные расстройства центральной нервной системы, включая расстройство спектра нейромиелита, расстройство спектра и болезнь миэлина олигодендроцита гликопротеина, связанные с антителами, характеризуются повреждениями имунной ткани, глиальной дисфункцией, метаболическим стрессом и неполным ремонтом. Хотя периферическая иммунная инфильтрация и антителные механизмы объясняют многие аспекты образования острых повреждений, они не в полной мере учитывают стойкую активность повреждения, метаболическую нестабильность или отказ от ремиэлирования в местно

NKG2D-CAR-transduced natural killer cells efficiently target multiple myeloma.

CAR-T-cell therapy against MM currently shows promising results, but usually with serious toxicities. CAR-NK cells may exert less toxicity when redirected against resistant myeloma cells. CARs can be designed through the use of receptors, such as NKG2D, which recognizes a wide range of ligands to provide broad target specificity. Here, we test this approach by analyzing the antitumor activity of activated and expanded NK cells (NKAE) and CD45RA- T cells from MM patients that were engineered to express an NKG2D-based CAR. NKAE cells were cultured with irradiated Clone9.mbIL21 cells. Then, cells

UFMTrack, "Недоходный миграционный трекер", позволяющий проанализировать весь многоэтапный каскад экстравазии иммунных клеток через барьер кровеносного мозга в микрофлюидовых устройствах.

Эндотелиальный барьер кровеносного мозга (БДБ) строго контролирует оборот иммунных клеток в центральную нервную систему (КНС). В таких нейро-воспалительных заболеваниях, как множественный склероз, этот жесткий контроль, однако, нарушается, что приводит к инфильтрации иммунных клеток в CNS. Разработка моделей BBB in vitro в сочетании с микрофлюидовыми устройствами способствовала более глубокому пониманию клеточных и молекулярных механизмов посредничества многоэтапной экстравазии Т-клеток по всему BBB. Одним из основных узких мест в этих исследованиях in vitro является отсутствие надежного и авт

Preoperative stereotactic radiosurgery for brain metastases: the STEP study protocol for a multicentre, prospective, phase-II trial.

BackgroundSurgery is an important therapeutic option for brain metastases. Currently, postoperative stereotactic radiosurgery (SRT) leads to 6-month and 1-year local control estimated at 70 and 62% respectively. However, there is an increased risk of radio-necrosis and leptomeningeal relapse. Preoperative SRT might be an alternative, providing local control remains at least equivalent. It is an innovative concept that could enable the stereotactic benefits to be retained with advantages over post-operative SRT.MethodsSTEP has been designed as a national, multicentre, open-label, prospective, n

Anti-cancer mechanisms of action of therapeutic alternating electric fields (tumor treating fields [TTFields]).

Despite improved survival outcomes across many cancer types, the prognosis remains grim for certain solid organ cancers including glioblastoma and pancreatic cancer. Invariably in these cancers, the control achieved by time-limited interventions such as traditional surgical resection, radiation therapy, and chemotherapy is short-lived. A new form of anti-cancer therapy called therapeutic alternating electric fields (AEFs) or tumor treating fields (TTFields) has been shown, either by itself or in combination with chemotherapy, to have anti-cancer effects that translate to improved survival outc

Monitoring the neurological complications of chimeric antigen receptor (CAR) T-cell therapy in patients with sensory and physical impairments and non-native-speaking backgrounds using modified immune effector cell-associated encephalopathy (ICE) scores: a case series.

BackgroundImmune effector cell-associated neurotoxicity syndrome (ICANS) is a common complication of chimeric antigen receptor (CAR) T-cell therapy. Current practice guidelines recommend the immune effector cell-associated encephalopathy (ICE) score for the assessment and monitoring of ICANS.ObjectiveTo demonstrate modifications to ICE score to patients with vision and hearing impairments or who are who are from non-native-speaking backgrounds.MethodsWe discuss five cases and the modifications made to adapt the ICE score to meet patients' needs.ResultsModifications to ICE score was feasible an

Clinical characteristics of older patients with COVID-19: a systematic review of case reports.

In the context of the current COVID-19 pandemic, higher morbidity and mortality have been reported in older adults. This age group presents physiological changes and its own clinical conditions such as frailty, dementia, among others.ObjectiveTo describe the characteristics of COVID-19 patients, both over and under 80 years old, by conducting a systematic review of the literature describing case reports, and to summarize and critically assess these characteristics.MethodsSystematic review. The study was registered on the Registry of Health Research Projects (PRISA) of the Peruvian National Ins

Orbital Onslaught: An Atypical Presentation of Mucormycosis in a Diabetic and Hypertensive Patient.

Mucormycosis, primarily known to affect the sinuses and brain, severely threatens immunocompromised individuals. Its occurrence in the orbital region is rare and potentially devastating. We report a unique case of a 50-year-old male with longstanding diabetes and hypertension who exhibited isolated orbital mucormycosis confined to the right eye. The patient presented with fever and acute vision loss without classic sinusitis symptoms; earlier mismanagement led to an aggressive relapse. An orbital computed tomography (CT) scan revealed inflammatory changes indicative of an early-stage invasive