Development of desmoid tumours after ileorectal anastomosis versus ileal pouch-anal anastomosis in familial adenomatous polyposis.

BACKGROUND & AIMS: Desmoid tumours (DT) are an important cause of morbidity and mortality in patients with familial adenomatous polyposis (FAP). DT development might be related to the type and approach of colectomy. We aimed to compare DT development after colectomy with ileorectal anastomosis (IRA) and proctocolectomy with ileal pouch-anal anastomosis (IPAA). METHODS: We performed an international historical cohort study in FAP patients who underwent IRA or IPAA between 1961 and 2020. The primary outcome was the incidence of abdominal DT (either mesenteric, retroperitoneal or abdominal wall). Patients with a DT diagnosis before or at colectomy were excluded. Time to DT was considered censored at an eventual secondary proctectomy after IRA. We used multivariable Cox regression modelling to adjust for potential confounders. RESULTS: We analysed data from 852 patients: 514 after IRA and 338 after IPAA (median follow-up 21 and 16 years, respectively). DTs were diagnosed in 64 IRA patients (12%) and 66 IPAA patients (20%). The cumulative DT incidence at 5 and 10 years was 7.5% and 9.3% after open IRA and 4.7% and 10.9% after laparoscopic IRA. These estimates were 13.6% and 15.4% after open IPAA and 8.4% and 10.0% after laparoscopic IPAA. The post-operative risk was significantly higher after IPAA (p < 0.01) in multivariable analysis, while approach did not significantly influence the risk. CONCLUSIONS: The risk of developing an abdominal DT was found to be significantly higher after IPAA than after IRA. Postoperative DT risk should be taken into account when choosing between IRA and IPAA in FAP.

Arabidopsis DNA glycosylase MBD4L improves recovery of aged seeds.

DNA glycosylases initiate the base excision repair (BER) pathway by catalyzing the removal of damaged or mismatched bases from DNA. The Arabidopsis DNA glycosylase methyl-CpG-binding domain protein 4 like (MBD4L) is a nuclear enzyme triggering BER in response to the genotoxic agents 5-fluorouracil and 5-bromouracil. To date, the involvement of MBD4L in plant physiological processes has not been analyzed. To address this, we studied the enzyme functions in seeds. We found that imbibition induced the MBD4L gene expression by generating two alternative transcripts, MBD4L.3 and MBD4L.4. Gene activation was stronger in aged than in non-aged seeds. Seeds from mbd4l-1 mutants displayed germination failures when maintained under control or ageing conditions, while 35S:MBD4L.3/mbd4l-1 and 35S:MBD4L.4/mbd4l-1 seeds reversed these phenotypes. Seed nuclear DNA repair, assessed by comet assays, was exacerbated in an MBD4L-dependent manner at 24 h post-imbibition. Under this condition, the BER genes ARP, APE1L, and LIG1 showed higher expression in 35S:MBD4L.3/mbd4l-1 and 35S:MBD4L.4/mbd4l-1 than in mbd4l-1 seeds, suggesting that these components could coordinate with MBD4L to repair damaged DNA bases in seeds. Interestingly, the ATM, ATR, BRCA1, RAD51, and WEE1 genes associated with the DNA damage response (DDR) pathway were activated in mbd4l-1, but not in 35S:MBD4L.3/mbd4l-1 or 35S:MBD4L.4/mbd4l-1 seeds. These results indicate that MBD4L is a key enzyme of a BER cascade that operates during seed imbibition, whose deficiency would cause genomic damage detected by DDR, generating a delay or reduction in germination.

Evolution of biotechnological advances and regenerative therapies for endometrial disorders: a systematic review.

BACKGROUND: The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) and intrauterine adhesions (IUA), or endometrial atrophy (EA) and thin endometrium (TE), can either originate autonomously or arise as a result from conditions (i.e. endometritis or congenital hypoplasia), or medical interventions (e.g. surgeries, hormonal therapies, uterine curettage or radiotherapy). Affected patients may present an altered or inadequate endometrial lining that hinders embryo implantation and increases the risk of poor pregnancy outcomes and miscarriage. In humans, AS/IUA and EA/TE are mainly treated with surgeries or pharmacotherapy, however the reported efficacy of these therapeutic approaches remains unclear. Thus, novel regenerative techniques utilizing stem cells, growth factors, or tissue engineering have emerged to improve reproductive outcomes. OBJECTIVE AND RATIONALE: This review comprehensively summarizes the methodologies and outcomes of emerging biotechnologies (cellular, acellular, and bioengineering approaches) to treat human endometrial pathologies. Regenerative therapies derived from human tissues or blood which were studied in preclinical models (in vitro and in vivo) and clinical trials are discussed. SEARCH METHODS: A systematic search of full-text articles available in PubMed and Embase was conducted to identify original peer-reviewed studies published in English between January 2000 and September 2023. The search terms included: human, uterus, endometrium, Asherman syndrome, intrauterine adhesions, endometrial atrophy, thin endometrium, endometritis, congenital hypoplasia, curettage, radiotherapy, regenerative therapy, bioengineering, stem cells, vesicles, platelet-rich plasma, biomaterials, microfluidic, bioprinting, organoids, hydrogel, scaffold, sheet, miRNA, sildenafil, nitroglycerine, aspirin, growth hormone, progesterone, and estrogen. Preclinical and clinical studies on cellular, acellular, and bioengineering strategies to repair or regenerate the human endometrium were included. Additional studies were identified through manual searches. OUTCOMES: From a total of 4366 records identified, 164 studies (3.8%) were included for systematic review. Due to heterogeneity in the study design and measured outcome parameters in both preclinical and clinical studies, the findings were evaluated qualitatively and quantitatively without meta-analysis. Groups using stem cell-based treatments for endometrial pathologies commonly employed mesenchymal stem cells (MSCs) derived from the human bone marrow or umbilical cord. Alternatively, acellular therapies based on platelet-rich plasma (PRP) or extracellular vesicles are gaining popularity. These are accompanied by the emergence of bioengineering strategies based on extracellular matrix (ECM)-derived hydrogels or synthetic biosimilars that sustain local delivery of cells and growth factors, reporting promising results. Combined therapies that target multiple aspects of tissue repair and regeneration remain in preclinical testing but have shown translational value. This review highlights the myriad of therapeutic material sources, administration methods, and carriers that have been tested. WIDER IMPLICATIONS: Therapies that promote endometrial proliferation, vascular development, and tissue repair may help restore endometrial function and, ultimately, fertility. Based on the existing evidence, cost, accessibility, and availability of the therapies, we propose the development of triple-hit regenerative strategies, potentially combining high-yield MSCs (e.g. from bone marrow or umbilical cord) with acellular treatments (PRP), possibly integrated in ECM hydrogels. Advances in biotechnologies together with insights from preclinical models will pave the way for developing personalized treatment regimens for patients with infertility-causing endometrial disorders such as AS/IUA, EA/TE, and endometritis. REGISTRATION NUMBER: https://osf.io/th8yf/.

Enriching Eggs with Bioactive Compounds through the Inclusion of Grape Pomace in Laying Hens Diet: Effect on Internal and External Egg Quality Parameters.

(1) Background: Grapes and their associated by-products (such as grape pomace, GP) stand out for their polyphenol content, which makes them a source of bioactive compounds with antioxidant capacity. The aim of this research was to determine if the inclusion of 50 g/kg of GP in the diet of hens could enrich eggs with antioxidants and to study its effect on internal and external egg quality parameters. (2) Methods: A trial was conducted with two genetic lines of hens, which were fed either a control diet or a diet containing 50 g/kg of GP. Performance, internal and external egg quality, and egg yolk content of vitamins E and A and gallic acid were determined. (3) Results: In eggs laid by hens fed a GP diet, Haugh units and yolk color scores were enhanced, and eggshells became thinner, but without affecting the breaking strength. No dietary effect was observed on the vitamin contents of the yolk. A higher gallic acid content was observed in the yolks of eggs laid by hens fed the GP diet, suggesting that some dietary phenolic compounds could be transferred to the eggs. Hen genetics influenced egg weight, albumen Haugh units, shell thickness, and α- and γ-tocopherol concentration in yolks. (4) Conclusions: Dietary inclusion of GP improved the internal quality of eggs, enriching yolks with a phenolic compound but reducing shell thickness.

Comparison of Bone Mineral Density and Trabecular Bone Score in Patients with and without Vertebral Fractures and Differentiated Thyroid Cancer with Long-Term Serum Thyrotrophin-Suppressed Therapy.

INTRODUCTION: The study of BMD provides only partial information on bone health in patients undergoing TSH suppression therapy due to differentiated thyroid cancer (DTC). The trabecular bone score (TBS), a new parameter assessing bone microarchitecture, is proposed for studying bone in this context. This study aimed to analyze their long-term use in patients with DTC. METHODS: Bone mineral density (BMD) was measured by dual X-ray densitometry (DXA) and TBS was assessed with iNsigth software (version 2.0, MediImaps, France) in 145 postmenopausal patients with DTC. Vertebral fractures (VFs) were identified using a semi-quantitative X-ray method. RESULTS: The BMD at the end of this study did not differ from the initial measurement. However, the TBS decreased from 1.35 ± 0.1 to 1.27 ± 0.1 (p = 0.002). Increased levels of PTH, osteocalcin, and bone alkaline phosphatase (BAP) were observed, suggesting enhanced bone remodeling. There was an increase in the prevalence of osteoporosis and osteopenia (40.6% and 16.5% to 46.6% and 18.6%, respectively). The proportion of patients with partially degraded and totally degraded TBS increased from 31% and 15.1% to 48.9% and 24.8% by the end of this study. Among the 30 patients with VFs, there were no significant differences in age, body mass index (BMI), calcium intake, alcohol consumption, smoking, radioiodine, therapy, or thyroid parameters compared to those without VFs. The odds ratio for VFs increased with osteopenia (OR 2.63). Combining TBS with BMD did not improve discrimination. CONCLUSIONS: The TBS decreased while the BMD remained unchanged. The percentage of patients with osteoporosis and osteopenia, whether partially degraded or totally degraded, increased by the end of this study. The predominant discordance was found in partially degraded microarchitectures, with a higher proportion of osteopenic patients compared to those with normal or osteoporotic bone density. The AUC of the combination of TBS and BMD did not enhance discrimination. TBS, radioactive iodine therapy, and sedentary lifestyle emerged as the main distinguishing factors for DTC patients with VFs.

HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study.

HMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of HMGA1 for trabectedin in advanced soft-tissue sarcoma (STS) and the effect of inhibiting HMGA1 or the mTOR downstream pathway in trabectedin activity. The prognostic/predictive value of HMGA1 expression was assessed in a cohort of 301 STS patients at mRNA (n = 133) and protein level (n = 272), by HTG EdgeSeq transcriptomics and immunohistochemistry, respectively. The effect of HMGA1 silencing on trabectedin activity and gene expression profiling was measured in leiomyosarcoma cells. The effect of combining mTOR inhibitors with trabectedin was assessed on cell viability in vitro studies, whereas in vivo studies tested the activity of this combination. HMGA1 mRNA and protein expression were significantly associated with worse progression-free survival of trabectedin and worse overall survival in STS. HMGA1 silencing sensitized leiomyosarcoma cells for trabectedin treatment, reducing the spheroid area and increasing cell death. The downregulation of HGMA1 significantly decreased the enrichment of some specific gene sets, including the PI3K/AKT/mTOR pathway. The inhibition of mTOR, sensitized leiomyosarcoma cultures for trabectedin treatment, increasing cell death. In in vivo studies, the combination of rapamycin with trabectedin downregulated HMGA1 expression and stabilized tumor growth of 3-methylcholantrene-induced sarcoma-like models. HMGA1 is an adverse prognostic factor for trabectedin treatment in advanced STS. HMGA1 silencing increases trabectedin efficacy, in part by modulating the mTOR signaling pathway. Trabectedin plus mTOR inhibitors are active in preclinical models of sarcoma, downregulating HMGA1 expression levels and stabilizing tumor growth.

Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease.

Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.

Fighting thyrotoxicosis with therapeutic plasma exchange: A case report.

Thyrotoxicosis is the clinical condition resulting from an excess of thyroid hormones for any reason. The main causes are Graves-Basedow disease, toxic multinodular goitre and toxic adenoma. The medical treatment to control thyroid function includes antithyroid drugs, beta blockers, iodine solutions, corticosteroids and cholestyramine. Although therapeutic plasma exchange is not generally part of the therapy, it is an alternative as a preliminary stage before the definitive treatment. This procedure makes it possible to eliminate T4, T3, TSI, cytokines and amiodarone. In most cases, more than one cycle is necessary, either daily or every three days, until clinical improvement is observed. The effect on thyrotoxicosis is temporary, with an approximate duration of 24-48h. This approach has been proposed as a safe and effective alternative when the medical treatment is contraindicated or not effective, and when there is multiple organ failure or emergency surgery is required.

BraNet: a mobil application for breast image classification based on deep learning algorithms.

Mobile health apps are widely used for breast cancer detection using artificial intelligence algorithms, providing radiologists with second opinions and reducing false diagnoses. This study aims to develop an open-source mobile app named "BraNet" for 2D breast imaging segmentation and classification using deep learning algorithms. During the phase off-line, an SNGAN model was previously trained for synthetic image generation, and subsequently, these images were used to pre-trained SAM and ResNet18 segmentation and classification models. During phase online, the BraNet app was developed using the react native framework, offering a modular deep-learning pipeline for mammography (DM) and ultrasound (US) breast imaging classification. This application operates on a client-server architecture and was implemented in Python for iOS and Android devices. Then, two diagnostic radiologists were given a reading test of 290 total original RoI images to assign the perceived breast tissue type. The reader's agreement was assessed using the kappa coefficient. The BraNet App Mobil exhibited the highest accuracy in benign and malignant US images (94.7%/93.6%) classification compared to DM during training I (80.9%/76.9%) and training II (73.7/72.3%). The information contrasts with radiological experts' accuracy, with DM classification being 29%, concerning US 70% for both readers, because they achieved a higher accuracy in US ROI classification than DM images. The kappa value indicates a fair agreement (0.3) for DM images and moderate agreement (0.4) for US images in both readers. It means that not only the amount of data is essential in training deep learning algorithms. Also, it is vital to consider the variety of abnormalities, especially in the mammography data, where several BI-RADS categories are present (microcalcifications, nodules, mass, asymmetry, and dense breasts) and can affect the API accuracy model.

Utility of ultrasound in the diagnostic approach to lymphoma with splenic involvement.

This paper describes the clinical case of a patient diagnosed with diffuse large B-cell lymphoma with splenic involvement, focusing on the role of abdominal ultrasound (US) in this context. The patient experienced dyspepsia and progressive asthenia over several months so an abdominal US was performed. The US showed multiple heterogeneous and hypoechogenic focal splenic lesions together with a moderate left pleural effusion. Lymphoma was suspected due to these findings and the diagnosis was then confirmed with the performance of a CT scan and a biopsy that revealed the presence of a diffuse large B-cell lymphoma with metastatic disease. Chemotherapy containing rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone was administered and the patient is currently on clinical remission. This study highlights the role of abdominal ultrasound as a useful technique in the non-invasive assessment of this entity, considering an appropriate clinical context and mainly after detecting multiple hypoechogenic splenic lesions in the US.

Transcriptomics of Besnoitia besnoiti-Infected Fibroblasts Reveals Hallmarks of Early Fibrosis and Cancer Progression.

Endothelial injury, inflammatory infiltrate and fibrosis are the predominant lesions in the testis of bulls with besnoitiosis that may result in sterility. Moreover, fibroblasts, which are key players in fibrosis, are parasite target cells in a Besnoitia besnoiti chronic infection. This study aimed to decipher the molecular basis that underlies a drift toward fibrosis during the disease progression. Transcriptomic analysis was developed at two times post-infection (p.i.), representative of invasion (12 h p.i.) and intracellular proliferation (32 h p.i.), in primary bovine aorta fibroblasts infected with B. besnoiti tachyzoites. Once the enriched host pathways were identified, we studied the expression of selected differentially expressed genes (DEGs) in the scrotal skin of sterile infected bulls. Functional enrichment analyses of DEGs revealed shared hallmarks of cancer and early fibrosis. Biomarkers of inflammation, angiogenesis, cancer, and MAPK signaling stood out at 12 h p.i. At 32 h p.i., again MAPK and cancer pathways were enriched together with the PI3K-AKT pathway related to cell proliferation. Some DEGs were also regulated in the skin samples of naturally infected bulls (PLAUR, TGFß1, FOSB). We have identified potential biomarkers and host pathways regulated during fibrosis that may hold prognostic significance and could emerge as potential therapeutic targets.

Hospital-based screening outperforms primary care screening as a means of achieving hepatitis C virus micro-elimination.

AIM: To assess the respective performances of a HCV screening program in a hospital setting and a HCV screening model applied concomitantly in a primary care centre. METHODS: Adult patients consecutively admitted to hospital for ambulatory surgery were screened for anti-HCV antibodies (hospital screening cohort, HPSC), as were patients receiving blood tests for medical reasons in a primary care centre (primary care screening cohort, PCSC). Serum anti-HCV and HCV RNA levels were tested by ELISA and real-time PCR, respectively. RESULTS: Seroprevalence of HCV infection was 2.2 % in the HPSC and 1.4 % in the PCSC (p = 0.044). All viraemic patients (0.2 % in HPSC and 0.1 % in PCSC) were treated with direct-acting antivirals and 85.7 % experienced a sustained virological response. CONCLUSIONS: Hospital-based HCV screening outperformed primary care-centered screening, significantly increasing HCV case findings.

Olive Pomace Oil Structuring for the Development of Healthy Puff Pastry Laminating Fats: The Effect of Chilling Storage on the Quality of Baked Products.

Developing puff pastry (PP) laminating fats (LFs) with sustainable structured olive pomace oil (OPO) could contribute to its increased valorization. This study evaluated the physicochemical stability of four OPO-based LFs or margarines and the performance of their baked PP counterparts during two months of chilling storage at 4 °C. LF samples, developed at the laboratory scale, contained 41% (LF1 and LF2) OPO and 31% (LF3 and LF4) OPO together with 10% cocoa butter when using two static initial crystallization conditions (room temperature for LF1 and LF3, freezer for LF2 and LF4) before storage. During the storage period, the proximate composition, thermal and dynamic rheological properties, firmness and spreadability, oil-binding capacity, color, and lipid oxidation of the four LF samples were examined, along with the baking performance and textural properties of the PP counterparts. The initial cooling rate had minimal significance. Cocoa butter negatively influenced post-crystallization processes occurring in OPO-based LF3 and LF4, resulting in increased hardness and reduced performance after 18 days of storage, attributed, at least partially, to a high amount of 1,3-dipalmitoyl-2-oleoyl-glycerol (POP), mainly from cocoa butter. Conversely, OPO-based LF1 and LF2 maintained their quality and were stable for two months without apparent granular crystal formation.

Trasplante de médula ósea haploidéntico en un paciente pediátrico con síndrome de Wiskott-Aldrich. A propósito de un caso / Haploidentical bone marrow transplantation in a pediatric patient with Wiskott-Aldrich syndrome. A case report

El síndrome de Wiskott-Aldrich es un error innato de la inmunidad de herencia ligada al cromosoma X, producido por variantes en el gen que codifica la proteína del síndrome de Wiskott-Aldrich (WASp). Reportamos el caso clínico de un paciente de 18 meses con diagnóstico de Wiskott-Aldrich que no presentaba donante antígeno leucocitario humano (HLA) idéntico y recibió un trasplante de células progenitoras hematopoyéticas (TCPH) con donante familiar haploidéntico. La profilaxis para enfermedad de injerto contra huésped incluyó ciclofosfamida (PT-Cy). El quimerismo del día +30 fue 100 % del donante y la evaluación postrasplante de la expresión de la proteína WAS fue normal. Actualmente, a 32 meses del trasplante, presenta reconstitución hematológica e inmunológica y quimerismo completo sin evidencia de enfermedad injerto contra huésped. El TCPH haploidéntico con PT-Cy se mostró factible y seguro en este caso de síndrome de WiskottAldrich en el que no se disponía de un donante HLA idéntico.

Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp). Here, we report the clinical case of an 18-month-old boy diagnosed with Wiskott-Aldrich syndrome, who did not have an HLA-matched related or unrelated donor and was treated successfully with a hematopoietic stem cell transplant (HSCT) from a haploidentical family donor. Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PT-Cy). At day +30, the peripheral blood-nucleated cell chimerism was 100% and the WAS protein had a normal expression. Currently, at month 32 post-transplant, the patient has hematological and immune reconstitution and complete donor chimerism without evidence of GvHD. HSCT with PT-Cy was a feasible and safe option for this patient with WAS, in which an HLA matched donor was not available.

Haploidentical bone marrow transplantation in a pediatric patient with Wiskott-Aldrich syndrome. A case report. / Trasplante de médula ósea haploidéntico en un paciente pediátrico con síndrome de Wiskott-Aldrich. A propósito de un caso.

Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp). Here, we report the clinical case of an 18-month-old boy diagnosed with Wiskott-Aldrich syndrome, who did not have an HLA-matched related or unrelated donor and was treated successfully with a hematopoietic stem cell transplant (HSCT) from a haploidentical family donor. Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PT-Cy). At day +30, the peripheral blood-nucleated cell chimerism was 100% and the WAS protein had a normal expression. Currently, at month 32 post-transplant, the patient has hematological and immune reconstitution and complete donor chimerism without evidence of GvHD. HSCT with PT-Cy was a feasible and safe option for this patient with WAS, in which an HLA matched donor was not available.

El síndrome de Wiskott-Aldrich es un error innato de la inmunidad de herencia ligada al cromosoma X, producido por variantes en el gen que codifica la proteína del síndrome de Wiskott-Aldrich (WASp). Reportamos el caso clínico de un paciente de 18 meses con diagnóstico de Wiskott-Aldrich que no presentaba donante antígeno leucocitario humano (HLA) idéntico y recibió un trasplante de células progenitoras hematopoyéticas (TCPH) con donante familiar haploidéntico. La profilaxis para enfermedad de injerto contra huésped incluyó ciclofosfamida (PT-Cy). El quimerismo del día +30 fue 100 % del donante y la evaluación postrasplante de la expresión de la proteína WAS fue normal. Actualmente, a 32 meses del trasplante, presenta reconstitución hematológica e inmunológica y quimerismo completo sin evidencia de enfermedad injerto contra huésped. El TCPH haploidéntico con PT-Cy se mostró factible y seguro en este caso de síndrome de WiskottAldrich en el que no se disponía de un donante HLA idéntico.

Linked-color imaging versus high definition white-light endoscopy for evaluation of post-polypectomy scars of nonpedunculated lesions: LCI-Scar study.

BACKGROUND: Detection and treatment of recurrence after piecemeal endoscopic mucosal resection of nonpedunculated colorectal polyps are crucial for avoidance of post-colonoscopy cancer. Linked-color imaging (LCI) has demonstrated improved polyp detection but has never been assessed for evaluation of post-polypectomy scars. Our aim was to compare sensitivity and negative predictive value (NPV) between LCI and white-light endoscopy (WLE) for detection of post-polypectomy recurrence. METHODS: Patients undergoing surveillance colonoscopy after resection of lesions ≥15 mm were included in this prospective, single-center, randomized, crossover study. Each post-polypectomy scar underwent two examinations, one with LCI and the other with WLE, performed by two blinded endoscopists. Blue-light imaging (BLI) was then applied. A diagnosis of recurrence with a level of confidence was made for each modality and histopathology was the gold standard. RESULTS: 129 patients with 173 scars were included. Baseline patient, lesion, and procedural characteristics were similar in both arms. Recurrence was detected in 56/173 (32.4%), with 27/56 (48.2%) adenomas and 29/56 (51.8%) serrated lesions. LCI had greater sensitivity (96.4% [95%CI 87.8%-99.5%]) versus WLE (89.3% [95%CI 78.1%-95.9%]) and greater NPV (98.1% [95%CI 93.4%-99.8%] versus 94.6% [95%CI 88.7%-98.0%]). Paired concordance between modalities was 96.0%. In discordant cases, LCI identified four true-positive cases not detected by WLE and reclassified one false-positive of WLE. WLE reclassified two false positives of LCI without any increase in recurrence detection. CONCLUSIONS: LCI was highly accurate and had greater ability than WLE to rule out recurrence on post-polypectomy scars after resection of large polyps.

Automated artificial intelligence-based three-dimensional comparison of orthodontic treatment outcomes with and without piezocision surgery.

OBJECTIVE(S): This study aims to evaluate the influence of the piezocision surgery in the orthodontic biomechanics, as well as in the magnitude and direction of tooth movement in the mandibular arch using novel artificial intelligence (AI)-automated tools. MATERIALS AND METHODS: Nineteen patients, who had piezocision performed in the lower arch at the beginning of treatment with the goal of accelerating tooth movement, were compared to 19 patients who did not receive piezocision. Cone beam computed tomography (CBCT) and intraoral scans (IOS) were acquired before and after orthodontic treatment. AI-automated dental tools were used to segment and locate landmarks in dental crowns from IOS and root canals from CBCT scans to quantify 3D tooth movement. Differences in mesial-distal, buccolingual, intrusion and extrusion linear movements, as well as tooth long axis angulation and rotation were compared. RESULTS: The treatment time for the control and experimental groups were 13.2 ± 5.06 and 13 ± 5.52 months respectively (P = .176). Overall, anterior and posterior tooth movement presented similar 3D linear and angular changes in the groups. The piezocision group demonstrated greater (P = .01) mesial long axis angulation of lower right first premolar (4.4 ± 6°) compared with control group (0.02 ± 4.9°), while the mesial rotation was significantly smaller (P = .008) in the experimental group (0.5 ± 7.8°) than in the control (8.5 ± 9.8°) considering the same tooth. CONCLUSION: The open source-automated dental tools facilitated the clinicians' assessment of piezocision treatment outcomes. The piezocision surgery prior to the orthodontic treatment did not decrease the treatment time and did not influence in the orthodontic biomechanics, leading to similar tooth movements compared to conventional treatment.

Testimonio profesional de la psicología de la salud en la región central de Cuba. (1964-2023)

Fundamento: las llamadas provincias de Las Villas y La Habana atesoran las primeras experiencias sobre la psicología en Cuba, después del triunfo de la Revolución; aunque esta historia ha sido insuficientemente divulgada en la región central del país. Objetivo: identificar aspectos distintivos de la psicología de la salud desde 1964 hasta 2023 en la antigua provincia de Las Villas, y posteriormente, en Villa Clara. Métodos: se realizó una investigación de tipo histórico en la Universidad de Ciencias Médicas de Villa Clara, entre enero-marzo 2023. Se emplearon métodos teóricos y empíricos: investigación documental en fuentes históricas de probada veracidad, entrevistas a informantes clave y testimonios de las autoras. Resultados: en el curso 1968-1969 se insertó la Psicología en los programas del Ministerio de Salud Pública, en La Habana y Las Villas. A partir de la fundación de la Sociedad Nacional de Psicología de la Salud y la Filial de Las Villas (1975), la especialidad ha ido en progreso: la graduación de varios especialistas, realización de cuatro maestrías y una línea de investigación doctoral, varios eventos con participación internacional, los intercambios científicos con otras universidades, y la acreditación de la especialidad son algunos de los avances que la distinguen. Conclusiones: la psicología de la salud en la región central de Cuba ha ido en ascenso desde su fundación. Sus logros en los escenarios científicos y académicos se han fortalecido bajo la dirección de un grupo de fundadores que con creatividad y responsabilidad se han convertido en promotores y actores de sus éxitos.

Background: the so-called provinces of Las Villas and Havana treasure the first experiences on health psychology in Cuba; although this story has been insufficiently disseminated in the central region of the country. Objective: to identify distinctive aspects of health psychology from 1964 to 2023 in the former province of Las Villas, and later, in Villa Clara. Methods: a historical research was carried out at Villa Clara University of Medical Sciences, from January to March 2023. Theoretical methods were used: analysis-synthesis, induction-deduction, historical-logical and systemic; empirical: documentary research in historical sources of proven veracity, interviews with key informants and testimonies of the authors. Results: in the 1968-1969 academic year, Psychology was inserted into the programs of the Ministry of Public Health, in Havana and Las Villas. Since the founding of the National Society of Health Psychology and the Las Villas Branch in 1975, the specialty has been in progress: the graduation of several specialists, completion of four master's degrees and a line of doctoral research, several events with participation International exchange, scientific exchanges with other universities, and the accreditation of the specialty are some of the advances that distinguish it. Conclusions: health psychology in the central region of Cuba has been on the rise since its foundation. Its achievements in the scientific and academic scenarios have been strengthened under the direction of a group of founders who, with creativity and responsibility, have become promoters and actors of its successes.

Superoxide, nitric oxide and peroxynitrite production by macrophages under different physiological oxygen tensions.

Macrophages count on two O2-consuming enzymes to form reactive radical species: NAPDH oxidase 2 (Nox2) and nitric oxide synthase 2 (inducible isoform, iNOS) that produce superoxide radical (O2•-) and nitric oxide (•NO), respectively. If formed simultaneously, the diffusion-controlled reaction of O2•- and •NO yields peroxynitrite, a potent cytotoxic oxidant. In human tissues and cells, the oxygen partial pressure (pO2) normally ranges within 2-14 %, with a typical average pO2 value for most tissues ca. 5 %. Given that O2 is a substrate for both Nox2 and iNOS, its tissue and cellular concentration can affect O2•- and •NO production. Also, O2 is a modulator of the macrophage adaptative response and may influence iNOS expression in a hypoxia inducible factor 1-α (HIF1α-)-dependent manner. However, most of the reported experiments in cellula, analyzing the formation and effects of O2•- and •NO during macrophage activation and cytotoxicity towards pathogens, have been performed in cells exposed to atmospheric air supplemented with 5 % CO2; under these conditions, most cells are exposed to supraphysiologic oxygen tensions (ca. 20 % O2) which are far from the physiological pO2. Here, the role of O2 as substrate in the oxidative response of J774A.1 macrophages was explored upon exposure to different pO2 and O2•- and •NO formation rates were measured, obtaining a KM of 26 and 42 µM O2 for Nox2 and iNOS, respectively. Consequently, peroxynitrite formation was influenced by pO2, reaching a maximum at ≥ 10 % O2, but even at levels as low as 2 % O2, a substantial formation rate of this oxidant was detected. Indeed, the cytotoxic capacity of immunostimulated macrophages against the intracellular parasite T. cruzi was significant, even at low pO2 values, confirming the role of peroxynitrite as a potent oxidizing cytotoxin within a wide range of physiological oxygen tensions.