Isolated hypertelorism: Late surgical correction using the box osteotomy technique.

Background: Orbital hypertelorism is a rare congenital condition caused by craniofacial malformations. It consists of complete orbital lateralization, characterized by an increase in distance (above the 95th percentile) of the inner canthal (ICD), outer canthal, and interpupillary distances. It can be approached surgically, and the main techniques are box osteotomy and facial bipartition. The surgical procedure is usually performed before the age of 8. We describe here two patients who underwent late surgical correction using the box osteotomy technique. Case Description: Patient 1: A 13-year-old female presenting isolated hypertelorism with 5 cm ICD and left eye amblyopia. Patient 2: A 15-year-old female with orbital hypertelorism, 4.6 cm ICD, and nasal deformity. Both patients underwent orbital translocation surgery and had no neurological disorders. Conclusion: The article reports two cases of isolated hypertelorism treated late with the box osteotomy technique. Both surgeries were successful, with no postoperative complications. It appears that it is possible to obtain good surgical results even in patients who have not been able to undergo surgery previously.

Proximalization of Arterial Inflow for the Treatment of Limb Ischemia in a Transposed Femoral Arteriovenous Fistula-A Case Report.

INTRODUCTION: Femoral vein transposition is one of the final resorts for vascular access in patients with exhaustion of upper limb venous patrimony and central venous occlusive disease. Its major pitfalls include hemodialysis access-induced distal ischemia and infection. Surgical procedures may be warranted to preserve vascular access if ischemia develops. Several techniques are reported in the literature for femoral vein transposition. CASE REPORT: We expose an endoscopic femoral vein harvesting as an alternative to the single thigh incision in order to avoid its associated complications. In the setting of ischemia, proximalization of arterial inflow was used to manage femoral vein transposition associated limb ischemia. CONCLUSION: This case report aims to expose the aforementioned unreported surgical techniques for lower limb arteriovenous fistula, its advantages, and pitfalls, as well as considerations on its future use.

Opportunities for, and barriers to, uterus-preserving surgical techniques for placenta accreta spectrum.

INTRODUCTION: Placenta accreta spectrum (PAS) can lead to major peripartum morbidity. Appropriate management approaches depend on the clinical severity, each individual's preference, and the treating team's expertise. Peripartum hysterectomy is the most frequently used treatment option. However, it can impact psychological well-being and fertility. We investigated whether conservative treatment with focal resection or leaving the placenta in situ is associated with comparable or lower maternal morbidity than hysterectomy in centers of excellence within the International Society for placenta accreta spectrum (IS-PAS). Furthermore, a survey was conducted to explore potential barriers to conservative management in antenatal counseling and intraoperative decision-making. MATERIAL AND METHODS: Confirmed PAS cases in the prospective IS-PAS database from 22 registered centers between January 2020 and June 2022 were included in the analysis. A separate online survey with 21 questions was answered by the IS-PAS center experts about indications, diagnostic criteria, patient counseling, surgical practice, changes from the preoperative treatment plan, and why conservative management may not be offered. RESULTS: A total of 234 cases were included in the analysis: 186 women received hysterectomy and 38 women were treated by focal resection, and 10 by leaving the placenta in situ. Blood loss was lower in the focal resection group and in the placenta in situ group compared to the hysterectomy group (p = 0.04). 46.4% of the women initially planned for focal resection, and 35.7% of those initially planned for leaving the placenta in situ were ultimately treated by hysterectomy. Our survey showed that the IS-PAS centers preferred hysterectomy according to a woman's wishes (64%) and when they expected less blood loss and morbidity (41%). Eighteen percent of centers did not offer focal resection at all due to a lack of experience with this technique. Reasons for not offering to leave the placenta in situ were avoidance of unexpected reoperation (36%), puerperal infection (32%), or skepticism about the method (23%). CONCLUSIONS: Uterus-preserving treatment strategies such as focal resection appear to be safe alternatives to peripartum hysterectomy. However, less than half of the IS-PAS centers perform them. Acceptance of conservative treatments could be increased by standardized criteria for their implementation and by systematic training for PAS experts.

Temporal bone squamous cell carcinoma: Aggressive behavior coursing with cerebellar invasion and hydrocephalus.

Background: Temporal bone squamous cell carcinoma (TBSCC) is a very rare condition. The prognosis is dismal for advanced tumors. Due to its rarity, information in the literature is scarce. Here, we report a unique case of TBSCC with cerebellar invasion and hydrocephalus. Case Description: A 46-year-old reported right-sided hearing loss and a painful right retroauricular mass for 4 months. Magnetic resonance imaging revealed a 8.7 × 7.6 × 6.4 cm mass invading the right temporal and occipital bones. After a biopsy and 3 surgical procedures over 6 months, the diagnosis of TBSCC was obtained. Due to invasion of the cerebellar tissue and obstructive hydrocephalus, a ventriculoperitoneal shunt was performed. The patient was referred for adjuvant radiotherapy. However, palliative care was initiated due to tumor progression. Conclusion: We report a case of advanced TBSCC with poor prognosis despite surgical treatment and radiotherapy. More data are necessary to provide new and better treatment to these patients.

Integrating tumor and healthy epithelium in a micro-physiology multi-compartment approach to study renal cell carcinoma pathophysiology.

The advent of micro-physiological systems (MPS) in biomedical research has enabled the introduction of more complex and relevant physiological into in vitro models. The recreation of complex morphological features in three-dimensional environments can recapitulate otherwise absent dynamic interactions in conventional models. In this study we developed an advanced in vitro Renal Cell Carcinoma (RCC) that mimics the interplay between healthy and malignant renal tissue. Based on the TissUse Humimic platform our model combines healthy renal proximal tubule epithelial cells (RPTEC) and RCC. Co-culturing reconstructed RPTEC tubules with RCC spheroids in a closed micro-perfused circuit resulted in significant phenotypical changes to the tubules. Expression of immune factors revealed that interleukin-8 (IL-8) and tumor necrosis factor-alfa (TNF-α) were upregulated in the non-malignant cells while neutrophil gelatinase-associated lipocalin (NGAL) was downregulated in both RCC and RPTEC. Metabolic analysis showed that RCC prompted a shift in the energy production of RPTEC tubules, inducing glycolysis, in a metabolic adaptation that likely supports RCC growth and immunogenicity. In contrast, RCC maintained stable metabolic activity, emphasizing their resilience to external factors. RNA-seq and biological process analysis of primary RTPTEC tubules demonstrated that the 3D tubular architecture and MPS conditions reverted cells to a predominant oxidative phosphorylate state, a departure from the glycolytic metabolism observed in 2D culture. This dynamic RCC co-culture model, approximates the physiology of healthy renal tubules to that of RCC, providing new insights into tumor-host interactions. Our approach can show that an RCC-MPS can expand the complexity and scope of pathophysiology and biomarker studies in kidney cancer research.

The pFSH dose affects the efficiency of in vivo embryo production in Santa Inês ewes.

This study compared the follicular growth, superovulatory response, and in vivo embryo production after administering two doses of porcine follicle-stimulating hormone (pFSH) in Santa Inês ewes. The estrous cycle of 36 multiparous ewes was synchronized with the Day 0 protocol and superovulated with 133 mg (G133, n=18) or 200 mg (G200, n=18) of pFSH. Ultrasonographic evaluations of the ovaries were performed, ewes were mated and submitted to non-surgical embryo recovery. Viable blastocysts were stained with Nile Red and Hoechst. The G200 had a greater number of medium and large follicles, as well as a larger size of the third largest follicle. A total of 97.2% (35/36) of the ewes came into estrus and it was possible to transpose cervix in 80.6% (29/36). There were no effects of treatments in the response to superovulation, the proportion of ewes in which was possible to transpose the cervix, the number of corpora lutea, the number of anovulatory follicles, the proportion of ewes flushed with at least one recovered structure, number of recovered structures, number of viable embryos, viability rate, and recovery rate. The G200 ewes were in estrus for a longer period of time than the G133 ewes (54.0 ± 4.5 h vs. 40.3 ± 3.6 h) and produced more freezable embryos (6.5 ± 1.6 vs. 2.3 ± 0.7) than G133. Both doses promoted an efficient superovulatory response and did not affect embryonic lipid accumulation. The dose of 200 mg of pFSH showed greater potential to increase the superovulatory response, as it increased follicular recruitment and the recovery of freezable embryos.

Efficacy and Safety of an Autologous Micrografting Procedure for Management of Striae Distensae in Women.

INTRODUCTION: Striae distensae (SD), or stretch marks, are a common skin problem having a psychological impact and cosmetic concern, especially for women, in whom the prevalence is higher than in men. This study assessed the efficacy and safety of a single autologous micrografting treatment (AMT®) using Rigenera® technology for the management of SD. METHODS: This single-centre study included 10 healthy women between 24 and 65 years of age, with Fitzpatrick-Goldman skin types I-IV, who had visible SD in glutes/thighs. Each subject acted as their own control. The treatment procedure (microneedling + AMT) and the control procedure (no treatment) were performed on contralateral sides of the glutes/thighs, targeting matched and paired SD. Microneedling was carried out using Dermapen®, equipped with 32 needle heads set at 1.5 mm needle length. The AMT procedure involved extracting biopsies from the mastoid hair zone with a 2.5-mm dermal punch, followed by disaggregation of the biopsies in a physiological saline solution using the Rigeneracons. The disaggregated micrografts were then intradermally injected using 30G 4-mm needles, maintaining a distance of 1 cm between injection points, covering the entire marked treatment region. RESULTS: In the treated area, at 3 months post-procedure compared to pre-procedure, the following changes were observed, all with statistical significance (P ≤ 0.05): (a) significant reductions in skin roughness (Ra, - 15.9%; Rz, - 22.6%), skin luminance (- 2.0%), and blue-green color distribution (- 10.6%); (b) significant increases in skin microcirculation maximum value (+ 240.1%), skin hydration (+ 71.2%), skin elasticity (+ 216.5%), skin density (+ 34.3%), skin thickness (+ 26.0%), and hypodermis thickness (+ 29.9%). Furthermore, for each of the aforementioned parameters, there was a significantly greater improvement observed with the AMT procedure compared with microneedling at 3 months (all P ≤ 0.05). CONCLUSION: The AMT procedure using Rigenera technology resulted in an noticeable improvement in the SD appearance after 3 months in healthy women.

This was a study of the Autologous Micrografting Technology (AMT) procedure for management of SD. Striae distensae (SD) commonly known as stretch marks are visible linear scars on the skin arising from excessive stretching of the skin. They are a very common condition, especially in women, causing cosmetic concern and psychological discomfort. Ten healthy women with SD were included in the study and each subject acted as their own control. Matched and paired SD on contralateral sides of the glutes/thighs were identified for treatment and control. In the area identified for treatment, the skin was initially damaged by microneedling to enhance regeneration, followed by intradermal injection of disaggregated autologous micrografts. The micrografts for the AMT procedure were extracted from the mastoid hair zone and disaggregated in physiological saline solution using the Rigeneracons. In the control area, no treatment was performed. The efficacy of the AMT procedure was assessed at 1 and 3 months post-procedure using several validated methodologies. Three months after the AMT procedure, a significant increase was observed in skin hydration, elasticity, density, and thickness, as well as in hypodermis thickness and microcirculation maximum value compared with pre-procedure in the treated area. There also was a significant reduction in skin roughness, skin luminance, and blue-green color distribution at 3 months in the treated area. For each of these parameters, the improvement observed at 3 months was significantly higher with the AMT procedure compared with only microneedling. We showed that a single AMT procedure using Rigenera technology is useful in the management of SD.

Is Subcapital Realignment for Slipped Capital Femoral Epiphysis a Reproducible Technique? Midterm Results.

BACKGROUND: The modified Dunn procedure, which is based on the development of an extended retinacular flap containing the blood supply for the femoral head, allows anatomic reestablishment in patients with moderate to severe slipped capital femoral epiphysis (SCFE). Some controversy exists regarding the short-term to midterm risk of avascular necrosis (AVN) and other complications resulting from the surgical technique. QUESTIONS/PURPOSES: (1) What percentage of patients treated with an extended retinacular flap during the modified Dunn procedure for SCFE with a moderate (slip angle from 30° to 60°) or severe slip (slip angle equal or greater than 60°) develop symptomatic AVN, and what percentage underwent further surgery or had other complications? (2) What femoral head-neck alignment and position parameters relative to the greater trochanter are achieved after surgery? (3) Can we identify radiographic signs of osteoarthritis at a minimum of 4 years after surgery? METHODS: Between January 2006 and December 2018, we treated 61 patients for SCFE. During this time, we generally used the modified Dunn procedure when the slip angle was ≥ 30°. Based on this indication, the modified Dunn procedure was performed in 37 patients (41 hips) during that time period, and those patients were potentially eligible for this retrospective study. Because bilateral hips in the same patient are not statistically independent, for our analyses, we analyzed only the hip with the longer follow-up time. Of those who remained, 11% (4) were lost before the minimum study follow-up of 48 months or had incomplete datasets, leaving 89% (33) for analysis here at a median follow-up of 80 months (range 49 to 208 months). Periacetabular osteotomy or subtrochanteric rotational femoral osteotomy was added under the same anaesthesia time in 33% (11 patients). We added periacetabular osteotomy in 24% (8) when intraoperative anterior instability was present in external rotation. A femoral rotational osteotomy was added in 9% (3) when posterior instability was present in flexion and internal rotation. The mean ± standard deviation age at the time of surgery was 13 ± 1 years, and 33% (11 of 33) of patients were female. The mean slip angle was 51° ± 16º, and 15% (5) of hips had unstable slips, defined as an inability to walk with or without crutches. We documented chronic presentations in 82% (27) of patients, acute and chronic in 12% (4), and acute in 6% (2). The rate of symptomatic AVN was determined by reviewing all radiographs obtained at the latest follow-up interval. Further surgery and other complications were assessed through an electronic medical record review. Radiographic morphologic parameters were measured before surgery and at a minimum follow-up of 4 years by two senior orthopaedic surgeons. Radiographs obtained at the latest follow-up visit were also screened for signs of osteoarthritis by the same surgeons. RESULTS: At the latest follow-up, 3% (1 patient) of patients developed symptomatic AVN and underwent further surgery and 3% (1) underwent revision surgery for screw breakage after a high-energy fall. Postoperatively, the alpha angle was restored to 39º ± 6º, the anterior head-neck offset was restored to 8 ± 3 mm, the neck-shaft angle was 136º ± 6º, and the presence of a positive Klein line decreased from 64% (21 hips) to 0% (0 hips). No patients showed radiographic signs of osteoarthritis at the minimum follow-up of 4 years. CONCLUSION: In this series, the modified Dunn procedure in moderate and severe slips was a reproducible procedure, and few patients developed symptomatic AVN or experienced other complications. Hip morphology was restored, but a longer follow-up duration and a detailed analysis of the results from other centers is warranted to assess the possible long-term risk of progression to AVN or osteoarthritis. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Cost-Effectiveness Analysis of Abrocitinib Compared with Other Systemic Treatments for Severe Atopic Dermatitis in Spain.

INTRODUCTION: Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by itchy, painful, and dry skin. Despite the great number of available therapies, economic evaluations are still needed to provide evidence on their cost efficiency. This research aimed to evaluate the cost effectiveness of the Janus kinase (JAK) inhibitor abrocitinib (200 mg) compared with dupilumab (300 mg), tralokinumab (300 mg), baricitinib (2 and 4 mg), and upadacitinib (15 and 30 mg) for the treatment of patients with severe AD from the Spanish National Health System (NHS) perspective. METHODS: A hybrid model consisting of a decision tree linked to a Markov model was developed to estimate costs, quality-adjusted life-years (QALYs), total years in response and incremental cost-per-QALY gained (willingness-to-pay [WTP] threshold: €25,000/QALY). Adults with severe AD entered the decision tree and response (75% reduction in baseline Eczema Area and Severity Index score, EASI-75) was considered at 16 and 52 weeks. After this time, patients entered the Markov model (remainder of the 10-year time horizon), which consisted of three health states: maintenance with active therapy, subsequent treatment, or death. All costs were presented in 2022 euros (€). Additionally, cost per number-needed-to-treat (NNT) was calculated for abrocitinib and dupilumab based on a head-to-head post-hoc analysis. RESULTS: Abrocitinib 200 mg was dominant (i.e., lower incremental costs and higher incremental benefit) compared with all studied alternatives (dupilumab 300 mg, tralokinumab 300 mg, baricitinib 2 and 4 mg, upadacitinib 15 and 30 mg) with a QALYs gain of 0.49, 0.60, 0.64, 0.43, 0.45, and 0.08, respectively, and per-person costs savings of €22,097, €24,140, €14,825, €7,116, €12,805, and €45,189, respectively. Considering the WTP threshold, abrocitinib was dominant or cost effective compared with all alternatives for most simulations. Additionally, abrocitinib was dominant compared with all alternatives when evaluating the cost effectiveness over a 5-year time horizon. NNT showed that abrocitinib was dominant versus dupilumab. CONCLUSIONS: The results of the study show that abrocitinib is a cost-effective therapy compared with other JAK inhibitors and biological therapies from the Spanish NHS perspective.

Bovine Pericardium Treated with Polyethylene Glycol and Ethanol Versus Pericranium for Duraplasty: A Pilot Study in Supratentorial Neurosurgery.

BACKGROUND: Watertight closure of dura mater after intracranial surgery can avoid cerebrospinal fluid leakage and central nervous system infection and herniation. When primary closure is not possible, the pericranium is the preferential choice. When it is not available, a dural substitute becomes necessary. Bovine pericardium treated with polyethylene glycol and ethanol is herein tested as a dural substitute. METHODS: A pilot study comparing bovine pericardium with pericranium in supratentorial neurosurgery was performed. RESULTS: Twenty patients were initially allocated into a bovine pericardium group (group 1) or a pericranium group (group 2). Three patients from group 1 and 2 from group 2 had a loss of follow-up, being excluded. In the remaining 15 patients, epidemiological analysis demonstrated a male:female ratio of 3:4 and 4:4 for groups 1 and 2. Ages varied from 28 to 68 (Mean = 49.6) in group 1 and 40-80 (Mean = 61.2) in group 2, with a mean difference of 11.68 years (P = 0.09). Two cases of surgical site infection and 1 of hydrocephalus were observed. Although the calculated relative risk for complications was higher in group 1 (Relative Risk = 1.08), Fisher exact test demonstrated no statistically significant difference between groups (P = 1.00). Procedure mean time was 23 minutes and 11 seconds in group 1 versus 27 minutes and 55 seconds in group 2 (P = 0.47). Mean graft area was 13.17 and 6.23 cm2 in groups 1 and 2 (P = 0.02). CONCLUSIONS: Bovine pericardium treated with polyethylene glycol and ethanol was comparable to pericranium as a dural substitute. More studies are encouraged to certify our findings.

Enhancer-promoter interactions can form independently of genomic distance and be functional across TAD boundaries.

Topologically Associating Domains (TADs) have been suggested to facilitate and constrain enhancer-promoter interactions. However, the role of TAD boundaries in effectively restricting these interactions remains unclear. Here, we show that a significant proportion of enhancer-promoter interactions are established across TAD boundaries in Drosophila embryos, but that developmental genes are strikingly enriched in intra- but not inter-TAD interactions. We pursued this observation using the twist locus, a master regulator of mesoderm development, and systematically relocated one of its enhancers to various genomic locations. While this developmental gene can establish inter-TAD interactions with its enhancer, the functionality of these interactions remains limited, highlighting the existence of topological constraints. Furthermore, contrary to intra-TAD interactions, the formation of inter-TAD enhancer-promoter interactions is not solely driven by genomic distance, with distal interactions sometimes favored over proximal ones. These observations suggest that other general mechanisms must exist to establish and maintain specific enhancer-promoter interactions across large distances.

Reproductive seasonality of hair rams under tropical conditions: an alternative for non-seasonal lamb production?

Reproductive seasonality limits the periods of breeding on the year and, therefore, productive output. However, some breeds appear as probably non-seasonal. The aim of the study was to characterize the seasonal pattern of Santa Inês rams, including an ultrasound characterization of the reproductive tract, testosterone concentrations, and semen characteristics. Fifteen Santa Inês rams remained in a grazing system with concentrate supplementation, and measurements of the reproductive tract and ultrasound evaluation (biometrics and pixel intensity) of the testicles and accessory sex glands were monthly recorded. Computerized seminal evaluations were also performed monthly, and serum testosterone concentration was measured every 15 days. Body weight and condition remained stable throughout the year. In general, reproductive traits varied along the year and reached maximum values during autumn and minimum in spring. Despite that, as fresh semen remained with enough quality to breed all along the year, seasonality does not appear as a limiting factor to breed along the year. Therefore, Santa Inês rams can be used for all-year-round breeding or for crossbreeding when rams from other breeds decrease their fertilizing ability.

Placenta Accreta Spectrum Disorders - The Impact of the Creation of a Multidisciplinary Team on Maternal Outcomes in Portugal.

OBJECTIVE: To describe a cohort of placenta accreta spectrum (PAS) cases from a tertiary care institution and compare the maternal outcomes before and after the creation of a multidisciplinary team (MDT). METHODS: Retrospective study using hospital databases. Identification of PAS cases with pathological confirmation between 2010 and 2021. Division in two groups: standard care (SC) group - 2010-2014; and MDT group - 2015-2021. Descriptive analysis of their characteristics and maternal outcomes. RESULTS: During the study period, there were 53 cases of PAS (24 - SC group; 29 - MDT group). Standard care group: 1 placenta increta and 3 percreta; 12.5% (3/24) had antenatal suspicion; 4 cases had a peripartum hysterectomy - one planned due to antenatal suspicion of PAS; 3 due to postpartum hemorrhage. Mean estimated blood loss (EBL) was 2,469 mL; transfusion of packed red blood cells (PRBC) in 25% (6/24) - median 7.5 units. Multidisciplinary team group: 4 cases of placenta increta and 3 percreta. The rate of antenatal suspicion was 24.1% (7/29); 9 hysterectomies were performed, 7 planned due to antenatal suspicion of PAS, 1 after intrapartum diagnosis of PAS and 1 after uterine rupture following a second trimester termination of pregnancy. The mean EBL was 1,250 mL, with transfusion of PRBC in 37.9% (11/29) - median 2 units. CONCLUSION: After the creation of the MDT, there was a reduction in the mean EBL and in the median number of PRBC units transfused, despite the higher number of invasive PAS disorders.

OBJETIVO: Descrever uma coorte de casos do espectro do acretismo placentário (PAS) de uma instituição terciária e comparar os resultados maternos antes e depois da criação de uma equipa multidisciplinar (MDT). MéTODOS: Estudo retrospectivo utilizando bancos de dados hospitalares. Identificação de casos de PAS com confirmação patológica entre 2010 e 2021. Divisão em dois grupos: grupo Standard Care (SC) ­ 2010­2014; e grupo MDT ­ 2015­2021. Análise descritiva de suas características e desfechos maternos. RESULTADOS: Durante o período do estudo, houve 53 casos de PAS (24 - grupo SC; 29 - grupo MDT). Grupo Standard Care: 1 placenta increta e 3 percretas; 12,5% (3/24) tiveram suspeita anteparto; 4 casos tiveram histerectomia periparto ­ uma eletiva devido à suspeita anteparto de PAS; 3 devido a hemorragia pós-parto. A média de perda hemática estimada (EBL) foi de 2.469 mL; transfusão de concentrado eritrocitário (PRBC) em 25% (6/24) - mediana 7,5 unidades. Equipa multidisciplinar: 4 casos de placenta increta e 3 percretas. A taxa de suspeita anteparto foi de 24,1% (7/29); foram realizadas 9 histerectomias, 7 eletivas por suspeita anteparto de PAS, 1 após diagnóstico intraparto de PAS e 1 após rotura uterina após interrupção da gravidez no segundo trimestre. A EBL média foi de 1.250 mL, com transfusão de PRBC em 37,9% (11/29) - mediana de 2 unidades. CONCLUSãO: Após a criação da MDT, houve redução na média de EBL e na mediana do número de unidades de PRBC transfundidas, apesar do maior número de PAS invasivos.

Placenta Accreta Spectrum Disorders - The Impact of the Creation of a Multidisciplinary Team on Maternal Outcomes in Portugal / Patologia do espectro do acretismo placentário - O impacto da criação de uma equipa multidisciplinar nos desfechos maternos em Portugal

Abstract Objective To describe a cohort of placenta accreta spectrum (PAS) cases from a tertiary care institution and compare the maternal outcomes before and after the creation of a multidisciplinary team (MDT). Methods Retrospective study using hospital databases. Identification of PAS cases with pathological confirmation between 2010 and 2021. Division in two groups: standard care (SC) group - 2010-2014; and MDT group - 2015-2021. Descriptive analysis of their characteristics and maternal outcomes. Results During the study period, there were 53 cases of PAS (24 - SC group; 29 - MDT group). Standard care group: 1 placenta increta and 3 percreta; 12.5% (3/24) had antenatal suspicion; 4 cases had a peripartum hysterectomy - one planned due to antenatal suspicion of PAS; 3 due to postpartum hemorrhage. Mean estimated blood loss (EBL) was 2,469 mL; transfusion of packed red blood cells (PRBC) in 25% (6/24) - median 7.5 units. Multidisciplinary team group: 4 cases of placenta increta and 3 percreta. The rate of antenatal suspicion was 24.1% (7/29); 9 hysterectomies were performed, 7 planned due to antenatal suspicion of PAS, 1 after intrapartum diagnosis of PAS and 1 after uterine rupture following a second trimester termination of pregnancy. The mean EBL was 1,250 mL, with transfusion of PRBC in 37.9% (11/29) - median 2 units. Conclusion After the creation of the MDT, there was a reduction in the mean EBL and in the median number of PRBC units transfused, despite the higher number of invasive PAS disorders.

Resumo Objetivo Descrever uma coorte de casos do espectro do acretismo placentário (PAS) de uma instituição terciária e comparar os resultados maternos antes e depois da criação de uma equipa multidisciplinar (MDT). Métodos Estudo retrospectivo utilizando bancos de dados hospitalares. Identificação de casos de PAS com confirmação patológica entre 2010 e 2021. Divisão em dois grupos: grupo Standard Care (SC) - 2010-2014; e grupo MDT - 2015-2021. Análise descritiva de suas características e desfechos maternos. Resultados Durante o período do estudo, houve 53 casos de PAS (24 - grupo SC; 29 - grupo MDT). Grupo Standard Care: 1 placenta increta e 3 percretas; 12,5% (3/24) tiveram suspeita anteparto; 4 casos tiveram histerectomia periparto - uma eletiva devido à suspeita anteparto de PAS; 3 devido a hemorragia pós-parto. A média de perda hemática estimada (EBL) foi de 2.469 mL; transfusão de concentrado eritrocitário (PRBC) em 25% (6/24) - mediana 7,5 unidades. Equipa multidisciplinar: 4 casos de placenta increta e 3 percretas. A taxa de suspeita anteparto foi de 24,1% (7/29); foram realizadas 9 histerectomias, 7 eletivas por suspeita anteparto de PAS, 1 após diagnóstico intraparto de PAS e 1 após rotura uterina após interrupção da gravidez no segundo trimestre. A EBL média foi de 1.250 mL, com transfusão de PRBC em 37,9% (11/29) - mediana de 2 unidades. Conclusão Após a criação da MDT, houve redução na média de EBL e na mediana do número de unidades de PRBC transfundidas, apesar do maior número de PAS invasivos.

Study of the economic impact of cryptosporidiosis in calves after implementing good practices to manage the disease on dairy farms in Belgium, France, and the Netherlands.

Cryptosporidium spp. are widespread parasitic protozoans causing enteric infections in humans and animals. The parasites cause neonatal diarrhoea in calves, leading to a high mortality rate in the first three weeks. Losses are significant for farmers, but the cost of cryptosporidiosis remains poorly documented. In the absence of a vaccine, only preventive measures are available to farmers to combat the infection. This study, conducted between 2018 and 2021, aimed to evaluate the economic impact of Cryptosporidium spp. on European dairy farms and monitor changes in costs after implementing disease management measures. First, a field survey was carried out and questionnaires administered to 57 farmers in Belgium, France, and the Netherlands. The aim of the survey was to assess the losses associated with the occurrence of diarrhoea in calves aged between 3 days and 3 weeks. The economic impact of diarrhoea was calculated based on mortality losses, health expenditures, and additional labour costs. To refine the cost estimation specifically for Cryptosporidium spp., stool samples were collected from 10 calves per farm. The prevalence of Cryptosporidium spp. was determined, and the economic impact of diarrhoea was adjusted accordingly. The assumption was made that a certain percentage of costs was attributed to cryptosporidiosis based on the prevalence. These protocols were repeated at the end of the study to observe changes in costs. In the three years, the cost of diarrhoea for the 28 farms that stayed in the panel all along the study improved from €140 in 2018 to €106 on average per diarrhoeic calf in 2021. With a stable prevalence at 40%, the cost of cryptosporidiosis per infected calf decreased from €60.62 to €45.91 in Belgium, from €43.83 to €32.14 in France, and from €58.24 to €39.48 in the Netherlands. This represented an average of €15 saved per infected calf. The methodology employed in this study did not allow us to conclude that the improvement is strictly due to the implementation of preventive measures. However, with 11 million calves raised in the Interreg 2 Seas area covered by the study, it provided valuable insights into the economic burden of Cryptosporidium spp.

Renal Organic Anion Transporters 1 and 3 In Vitro: Gone but Not Forgotten.

Organic anion transporters 1 and 3 (OAT1 and OAT3) play a crucial role in kidney function by regulating the secretion of multiple renally cleared small molecules and toxic metabolic by-products. Assessing the activity of these transporters is essential for drug development purposes as they can significantly impact drug disposition and safety. OAT1 and OAT3 are amongst the most abundant drug transporters expressed in human renal proximal tubules. However, their expression is lost when cells are isolated and cultured in vitro, which is a persistent issue across all human and animal renal proximal tubule cell models, including primary cells and cell lines. Although it is well known that the overall expression of drug transporters is affected in vitro, the underlying reasons for the loss of OAT1 and OAT3 are still not fully understood. Nonetheless, research into the regulatory mechanisms of these transporters has provided insights into the molecular pathways underlying their expression and activity. In this review, we explore the regulatory mechanisms that govern the expression and activity of OAT1 and OAT3 and investigate the physiological changes that proximal tubule cells undergo and that potentially result in the loss of these transporters. A better understanding of the regulation of these transporters could aid in the development of strategies, such as introducing microfluidic conditions or epigenetic modification inhibitors, to improve their expression and activity in vitro and to create more physiologically relevant models. Consequently, this will enable more accurate assessment for drug development and safety applications.

Lissencephaly With Cerebellar Hypoplasia Due To a New RELN Mutation.

Lissencephaly with cerebellar hypoplasia (LCH) is a rare variant form of lissencephaly, its distinctive neuroradiological phenotype being an important investigation clue regarding the potential involved genes, including variants in RELN gene. We report on a case of LCH whose clinical and neuroradiological features led to the identification of a homozygous pathogenic variant in RELN gene that has not been previously reported in the scientific literature.

Frequency of CDH1, CTNNA1 and CTNND1 Germline Variants in Families with Diffuse and Mixed Gastric Cancer.

The most well-characterized hereditary form of gastric cancer is hereditary diffuse gastric cancer (HDGC), an autosomal dominant syndrome characterized by an increased risk of diffuse gastric and lobular breast cancer. HDGC is predominantly caused by germline pathogenic variants in the CDH1 gene, and more rarely in the CTNNA1 gene. Furthermore, the International Gastric Cancer Linkage Consortium (IGCLC) guidelines do not clarify whether or not mixed gastric cancer (with a diffuse component) should be considered in the HDGC genetic testing criteria. We aimed to evaluate the contribution of CTNNA1 and CTNND1 germline variants to HDGC. Additionally, we also intended to compare the frequencies of CDH1 and CTNNA1 (and eventually CTNND1) germline variants between patients with diffuse and mixed gastric carcinomas to evaluate if genetic testing for these genes should or should not be considered in patients with the latter. We analyzed the CDH1 gene in 67 cases affected with early-onset/familial mixed gastric carcinomas and the CTNNA1 and CTNND1 genes in 208 cases with diffuse or mixed gastric cancer who had tested negative for CDH1 pathogenic germline variants. A deleterious CTNNA1 germline variant was found in 0.7% (1/141) of diffuse gastric cancer patients meeting the 2020 IGCLC criteria, as compared to the rate of 2.8% of CDH1 deleterious variants found by us in this setting. No deleterious variants were found in CTNND1, but six variants of uncertain significance were identified in this gene. We did not find any pathogenic CDH1, CTNNA1 or CTNND1 variant in index patients with early-onset/familial mixed gastric cancer, so there is no evidence that supports including this tumor type in the testing criteria for germline variants in these genes. The role of the CTNND1 gene in inherited gastric cancer predisposition is still unclear.

Cost-Effective Resources for Computing Approximation Queries in Mobile Cloud Computing Infrastructure.

Answering a query through a peer-to-peer database presents one of the greatest challenges due to the high cost and time required to obtain a comprehensive response. Consequently, these systems were primarily designed to handle approximation queries. In our research, the primary objective was to develop an intelligent system capable of responding to approximate set-value inquiries. This paper explores the use of particle optimization to enhance the system's intelligence. In contrast to previous studies, our proposed method avoids the use of sampling. Despite the utilization of the best sampling methods, there remains a possibility of error, making it difficult to guarantee accuracy. Nonetheless, achieving a certain degree of accuracy is crucial in handling approximate queries. Various factors influence the accuracy of sampling procedures. The results of our studies indicate that the suggested method has demonstrated improvements in terms of the number of queries issued, the number of peers examined, and its execution time, which is significantly faster than the flood approach. Answering queries poses one of the most arduous challenges in peer-to-peer databases, as obtaining a complete answer is both costly and time-consuming. Consequently, approximation queries have been adopted as a solution in these systems. Our research evaluated several methods, including flood algorithms, parallel diffusion algorithms, and ISM algorithms. When it comes to query transmission, the proposed method exhibits superior cost-effectiveness and execution times.