Transformers meets neoantigen detection: a systematic literature review.

Cancer immunology offers a new alternative to traditional cancer treatments, such as radiotherapy and chemotherapy. One notable alternative is the development of personalized vaccines based on cancer neoantigens. Moreover, Transformers are considered a revolutionary development in artificial intelligence with a significant impact on natural language processing (NLP) tasks and have been utilized in proteomics studies in recent years. In this context, we conducted a systematic literature review to investigate how Transformers are applied in each stage of the neoantigen detection process. Additionally, we mapped current pipelines and examined the results of clinical trials involving cancer vaccines.

[Overweight and obesity in children aged 5-11 years in Mexico - Why is necessary an interdisciplinary approach?] / Sobrepeso y obesidad en niños de 5 a 11 años en México en el periodo 1999-2021: ¿por qué es necesario un abordaje interdisciplinario?

INTRODUCTION: overweight and obesity in children are serious public health problems in Mexico. OBJECTIVE: to analyze the behavior of the prevalence of overweight and obesity in children from 5 to 11 years of age and to present projections on the prevalence for the period 2022-2026. METHODOLOGY: ecological and retrospective study whose units of analysis were groups of children of Mexico with overweight and obesity in the period 1999-2021, according to information collected from six National Health and Nutrition Surveys. For the projections the classical method of least squares was used, for a trend analysis of both conditions for the period 2022-2026. RESULTS: Overweight in girls and obesity in boys shows a high prevalence in the period 1999-2021, even though the trend analysis for the period 2022-2026 shows a slight decrease in overweight for the group of boys and a slight increase in overweight for girls, as well in obesity for both groups. CONCLUSIONS: due to the high prevalence of overweight and obesity in children from 5 to 11 years of age in Mexico, an interdisciplinary approach is required to identify which dimensions (biochemical, psychological, interpersonal and social) participate in the problem, considering three environments contributing for psychological and social development of children, the ecological-social, the family and the school.

Synthesis, In Silico Study, and In Vitro Antifungal Activity of New 5-(1,3-Diphenyl-1H-Pyrazol-4-yl)-4-Tosyl-4,5-Dihydrooxazoles.

The increase in multi-drug resistant Candida strains has caused a sharp rise in life-threatening fungal infections in immunosuppressed patients, including those with SARS-CoV-2. Novel antifungal drugs are needed to combat multi-drug-resistant yeasts. This study aimed to synthesize a new series of 2-oxazolines and evaluate the ligands in vitro for the inhibition of six Candida species and in silico for affinity to the CYP51 enzymes (obtained with molecular modeling and protein homology) of the same species. The 5-(1,3-diphenyl-1H-pyrazol-4-yl)-4-tosyl-4,5-dihydrooxazoles 6a-j were synthesized using the Van Leusen reaction between 1,3-diphenyl-4-formylpyrazoles 4a-j and TosMIC 5 in the presence of K2CO3 or KOH without heating, resulting in short reaction times, high compound purity, and high yields. The docking studies revealed good affinity for the active site of the CYP51 enzymes of the Candida species in the following order: 6a-j > 4a-j > fluconazole (the reference drug). The in vitro testing of the compounds against the Candida species showed lower MIC values for 6a-j than 4a-j, and for 4a-j than fluconazole, thus correlating well with the in silico findings. According to growth rescue assays, 6a-j and 4a-j (like fluconazole) inhibit ergosterol synthesis. The in silico toxicity assessment evidenced the safety of compounds 6a-j, which merit further research as possible antifungal drugs.

The impact of vascular margin invasion on local recurrence after pancreatoduodenectomy in pancreatic adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PADC) still has nowadays a very impaired long-term survival. Most studies are focused on overall survival; however, local recurrence occurs about up to 50% of cases and seems to be highly related with margin resection status. We aim to analyze the impact of vascular resection margins on local recurrence (LR) and to assess its impact on overall and disease-free survival. METHODS: Eighty out of 191 patients who underwent pancreatoduodenectomy in a university hospital between 2006 and 2021 with PDAC diagnosis were analyzed and vascular margin status specifically addressed. Univariate and multivariate were performed. Time to LR was compared by using the Kaplan-Meier method and prognostic factors assessed using Cox regression hazards model. RESULTS: LR appeared in 10 (50%) of the overall R1 resections in the venous margin and 9 (60%) in the arterial one. Time to LR was significantly shorter when any margin was overall affected (23.2 vs 44.7 months, p = 0.01) and specifically in the arterial margin involvement (13.7 vs 32.1 months, p = 0.009). Overall R1 resections (HR 2.61, p = 0.013) and a positive arterial margin (HR 2.84, p = 0.012) were associated with local recurrence on univariate analysis, whereas arterial positive margin remained significant on multivariate analysis (HR 2.70, p = 0.031). CONCLUSIONS: Arterial margin invasion is correlated in our cohort with local recurrence. Given the limited ability to modify this margin intraoperatively, preoperative therapies should be considered to improve local margin clearance.

Efficacy of Systemic Bevacizumab for Recurrent Respiratory Papillomatosis with Pulmonary Involvement.

OBJECTIVES: Pulmonary papillomatosis is a rare but severe manifestation of recurrent respiratory papillomatosis (RRP). Efficacy data of systemic bevacizumab for pulmonary RRP are limited. This study's objective was to characterize disease response of pulmonary RRP to systemic bevacizumab. METHODS: A retrospective review was performed to identify patients with pulmonary RRP seen at three medical institutions. Clinical symptoms, CT findings, and disease response were compared before and after initiation of systemic bevacizumab therapy. Disease response was categorized as complete response, partial response, stabilization, or progression for each subsite involved by papilloma. RESULTS: Of the 12 pulmonary RRP patients treated with systemic bevacizumab, 4 (33.3%) were male, and 11 (91.7%) were juvenile-onset RRP patients. All presented with laryngeal, tracheal, and pulmonary RRP. The median (range) age at first bevacizumab infusion was 48.1 (19.5-70.2) years. Progression to pulmonary malignancy was identified in 3 (25.0%) patients, 2 before initiation of and 1 after complete cessation of bevacizumab therapy. Clinical symptoms such as dyspnea (75.0% vs. 25.0%; p = 0.01) and dysphagia and/or odynophagia (33.3 vs. 0.0%; p = 0.03) were significantly decreased following bevacizumab therapy. Compared with pre-treatment baseline, 9 (75.0%) patients experienced a stable-to-partial response in the lungs to systemic bevacizumab, and 10 (83.3%) experienced partial-to-complete responses in the larynx and trachea. CONCLUSION: Systemic bevacizumab is effective in stabilizing progression in even the most severe cases of RRP, with both a dramatic reduction in laryngeal and tracheal disease as well as a stable-to-partial response of pulmonary involvement in a majority of patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:577-581, 2024.

The Humira in Ocular Inflammations Taper (HOT) Study.

PURPOSE: To assess factors that impact the risk of relapse in patients with noninfectious uveitis (NIU) who undergo adalimumab tapering after achieving remission. DESIGN: Retrospective study. METHODS: In this multicenter study, patients with NIU were treated with adalimumab and subsequently tapered. Patient demographics, type of NIU, onset and duration of disease, the period of inactivity before tapering adalimumab, and the tapering schedule were collected. The primary outcome measures were independent predictors of the rate of uveitis recurrence after adalimumab tapering. RESULTS: Three hundred twenty-eight patients were included (54.6% female) with a mean age of 34.3 years. The mean time between disease onset and initiation of adalimumab therapy was 35.2 ± 70.1 weeks. Adalimumab tapering was commenced after a mean of 100.8 ± 69.7 weeks of inactivity. Recurrence was observed in 39.6% of patients at a mean of 44.7 ± 61.7 weeks. Patients who experienced recurrence were significantly younger than those without recurrence (mean 29.4 years vs 37.5 years, P = .0005), and the rate of recurrence was significantly higher in younger subjects (hazard ratio [HR] = 0.88 per decade of increasing age, P = .01). The lowest rate of recurrence was among Asian subjects. A faster adalimumab taper was associated with an increased recurrence rate (HR = 1.23 per unit increase in speed, P < .0005). Conversely, a more extended period of remission before tapering was associated with a lower rate of recurrence (HR = 0.97 per 10-weeks longer period of inactivity, P = .04). CONCLUSIONS: When tapering adalimumab, factors that should be considered include patient age, race, and duration of disease remission on adalimumab. A slow tapering schedule is advisable.

Simultaneous unilateral central retinal vein occlusion and branch retinal artery occlusion after Coronavirus Disease 2019 (COVID-19) mRNA vaccine / Oclusão unilateral simultânea da veia retiniana central e artéria retiniana ramificada após vacina mRNA COVID-19

ABSTRACT A 51-year-old non-obese woman presented with a one-week history of progressive blurry vision within the inferior visual field of her left eye. Her only relevant past medical history was long-standing hypothyroidism and recent vaccination against Coronavirus Disease 2019 (COVID-19) with an mRNA vaccine 12 days before the onset of symptoms. At examination, the anterior segment was unremarkable, but the retinal fundus revealed a central retinal vein occlusion associated with a branch retinal artery occlusion of the superior temporal branch in her left eye. Ancillary tests to rule out thrombophilia, hyperviscosity, hypercoagulability, or inflammation were negative. Ultrasound tests were also negative for a cardiac or carotid origin of the branch retinal artery occlusion. At two-month follow-up, no new retinal vascular occlusive events were observed. Although the best-corrected visual acuity at presentation was 8/10 in the left eye, the final best-corrected visual acuity remained 3/10.

RESUMO Uma mulher de 51 anos, não obesa, apresentou história de uma semana de visão embaçada progressiva no campo visual inferior do olho esquerdo. Seu único histórico médico anterior relevante era hipotireoidismo de longa data e uma recente vacinação contra a Doença de Coronavírus 2019 (COVID-19), com vacina de mRNA, 12 dias antes do início dos sintomas. O exame mostrou segmento anterior normal, mas o fundo da retina revelou uma oclusão da veia central da retina associada a uma oclusão de ramo arterial da retina do ramo temporal superior no olho esquerdo. Testes auxiliares para descartar trombofilia, hiperviscosidade, hipercoagulabilidade ou inflamação apresentaram resultados negativos. Testes de ultrassom também foram negativos quanto a uma origem cardíaca ou da carótida da oclusão do ramo da artéria da retina. Após dois meses de acompanhamento, nenhum novo evento vascular oclusivo retiniano foi observado. Embora, a acuidade visual melhor corrigida na apresentação tenha sido de 8/10 no olho esquerdo, a acuidade visual final melhor corrigida permaneceu em 3/10.

Simultaneous removal of brominated and chlorinated species during the production of oils by e-waste plastics catalytic hydropyrolysis.

The production of added-value chemicals via pyrolysis of plastic wastes, such as those from electrical and electronic equipment (WEEE), needs addressing their usual contamination with halogens (mainly Br and Cl). This work compares the conversion via pyrolysis and hydropyrolysis of a real WEEE plastic, having a complex composition, in two different reactor configurations: down-flow (DF) and up-flow (UF). Likewise, the effects of incorporating a Pd/Al2O3 catalyst and using two different pressures (1 and 6 bar) have been assessed. With the DF mode, pyrolysis at 1 bar leads to an oil yield above 80 wt% and a total halogen content of about 600 ppm (vs 1600 ppm in the water-washed WEEE plastic). Under DF catalytic hydropyrolysis at 6 bar, this high oil yield is maintained while its dehalogenation degree is improved (142 ppm). Operating with the up-flow configuration, under 6 bar and H2 presence, leads to some reduction in the oil yield (about 70 wt%) but significantly decreases the oil halogen content (55 ppm Cl and total elimination of Br). These results have been related to the slower pyrolysis and longer residence time in the thermal zone of the UF configuration, which favours the halogen-trapping effect of the char fraction, and the pressure-enhanced hydrodehalogenation activity of the catalyst. This study highlights the environmental benefits of the proposed process, emphasizing the lower halogen content in the resulting oils and promoting a more sustainable approach to plastic waste valorisation.

Paracoccidoidomicosis: Reporte de 4 casos

La paracoccidioidomicosis (PCM) es una infección causada por hongos patógenos humanos del género Paracoccidioides. Es una micosis sistémica que puede afectar cualquier órgano. Se describen con este reporte cuatro casos de paracoccidioidomicosis con diferentes presentaciones clínicas, tiempo de evolución, con afectación mucocutánea, pulmonar, glándulas suprarrenales, sistema nervioso entre otros, principalmente en adultos varones de diferentes edades y profesiones, tanto inmunosuprimidos como inmunocompetentes, teniendo en común el contacto con el suelo. Se demuestra de esta manera la importancia de considerar esta patología ante una sospecha clínica de micosis sistémica para así realizar una confirmación temprana y tratamiento oportuno ya que presenta buena respuesta terapéutica antimicótica y mejoría clínica.

Paracoccidioidomycosis (PCM) is an infection caused by human pathogenic fungi of the genus Paracoccidioides. This report describes: 4 cases of paracoccidioidomycosis diagnosed with different clinical presentations, different times of evolution, with mucocutaneous, pulmonary, adrenal gland, and nervous system involvement, among others, mainly in male adults of different ages and professions, both immunosuppressed and immunocompetent, having in common contact with the ground. In this way, PCM is a systemic mycosis that can affect any organ and therefore the importance of considering this pathology when a diagnostic suspicion of systemic mycosis is presented in order to make an early diagnosis and timely treatment since it presents a good therapeutic response, antifungal and clinical improvement.

Meningiomas de ángulo pontocerebeloso: tratamiento con radiocirugía mediante LINAC / Cerebellopontine angle meningiomas: LINAC stereotactic radiosurgery treatment

Objetivos Evaluar el resultado del tratamiento con radiocirugía estereotáctica (RC) mediante acelerador lineal (LINAC) en meningiomas de ángulo pontocerebeloso (APC). Métodos Analizamos 80 pacientes diagnosticados de meningiomas de APC entre los años 2001-2014, tratados mediante RC. El 81,9% (n=68) fueron mujeres, con una media de edad de 59,1años (32-79). La RC se aplicó como tratamiento primario en el 83,7% (n=67), y en el 16,3% (n=13) como adyuvante a la cirugía. El tratamiento con RC se lleva a cabo en un acelerador lineal (Varian600, 6MeV) con micromultiláminas M3 (BrainLab) y marco estereotáxico. El volumen tumoral medio fue de 3,14cm3 (0,34-10,36cm3) y la dosis de cobertura media fue de 14Gy (12-16Gy). Se realiza un análisis descriptivo retrospectivo, un análisis de supervivencia método Kaplan-Meier y se contrasta la relación entre las variables del estudio mediante análisis univariados. Resultados Tras un periodo de seguimiento medio de 86,9meses (12-184), la tasa de control tumoral fue del 92,8% (n=77). Se comprobó una reducción global del volumen tumoral al final del estudio del 32,8%, con un volumen medio final de 2,11cm3 (0-10,35cm3). La tasa de supervivencia libre de progresión fue del 98% al año, del 95% a los 5años y del 83,3% a los 10 y 12años. El mayor volumen tumoral previo al tratamiento (p=0,047) se relacionó con la progresión. Se produjo la mejoría clínica en el 26,5% (n=21) de los casos y el deterioro en el 16,2% (n=13); el empeoramiento se relaciona con la dosis de radiación que recibe el troncoencéfalo (p=0,02). Respecto a las complicaciones, el 8,7% (n=7) sufrieron deterioro de la audición, el 5% (n=4) radionecrosis y el 3,7% (n=3) neuropatía del Vpar craneal. La dosis máxima alcanzada (p=0,037) y el tamaño tumoral inicial (p=0,033) se relacionan con la progresión de la hipoacusia, y el desarrollo de radionecrosis, con la dosis máxima alcanzada (p=0,037) (AU)

Objectives To evaluate the efficacy of treatment with linear accelerator-based stereotactic radiosurgery (LINAC) in cerebellopontine angle meningiomas. Methods We analyzed 80 patients diagnosed with cerebellopontine angle meningiomas between 2001 and 2014, treated with stereotactic radiosurgery (SRS), of whom 81.9% (n=68) were women, with an average age of 59.1years (32-79). SRS was applied as primary treatment in 83.7% (n=67) and in 16.3% (n=13) as an adjuvant treatment to surgery. SRS treatment was provided using LINAC (Varian600, 6MeV) with M3 micromultilamines (brainLab) and stereotactic frame. The average tumor volume was 3.12cm3 (0.34-10.36cm3) and the coverage dose was 14Gy (12-16Gy). We performed a retrospective descriptive analysis and survival analysis was performed with the Kaplan-Meier method and multivariate analysis to determine those factors predictive of tumor progression or clinical improvement. Results After an average follow-up period of 86.9months (12-184), the tumor control rate was 92.8% (n=77). At the end of the study, there was an overall reduction in tumor volume of 32.8%, with an average final volume of 2.11cm3 (0-10.35cm3). The progression-free survival rate at 5, 10 and 12years was 98%, 95% and 83.3% respectively. The higher tumor volume (P=.047) was associated with progression. There was clinical improvement in 26.5% (n=21) of cases and clinical worsening in 16.2% (n=13). Worsening is related to the radiation dose received by the brainstem (P=.02). Complications were 8.7% (7 cases) of hearing loss, 5% (4 cases) of brain radionecrosis, and 3.7% (3 cases) of cranial nerveV neuropathy. Hearing loss was related to initial tumor size (P=.033) and maximum dose (P=.037). The occurrence of radionecrosis with the maximum dose (P=.037). Conclusions Treatment of cerebellopontine angle meningiomas with single-dose SRS using LINAC is effective in the long term. Better tumor control rates were obtained in patients with small lesions (AU)

Pars plana vitrectomy in patients aged 85 years and older: a single-centre, retrospective cohort study.

PURPOSE: To describe the epidemiology, indications and surgical results of pars plana vitrectomy (PPV) in patients over 85 years of age. METHODS: A retrospective cohort study was performed including all consecutive patients aged 85 years or older who underwent PPV between September 2018 and March 2022 in a single hospital in Madrid, Spain. Data on diagnosis, comorbidities, surgical indication, surgical details, surgical complications and surgical outcomes were collected from medical records. RESULTS: A total of 124 eyes of 119 patients (56 males, 47.1%) underwent PPV. Median age was 87 years (range 85-96). The most common surgical indications were complications of cataract surgery in 34 patients (28.6%), macular epiretinal membrane in 32 (26.9%), and rhegmatogenous retinal detachment (RRD) in 12 (10.1%). Mean preoperative best corrected visual acuity (BCVA) was 13.33 ± 42.34 ETDRS letters and improved to 40.05 ± 41.04 letters at 3 months (p < 0.001). BCVA had improved in 68.82% of patients at 3 months. Patients with chronic kidney disease (CKD; p < 0.001), RRD (p = 0.003), ocular trauma (p = 0.001) and age-related macular degeneration (AMD; p = 0.002) showed worse BCVA at 3 months from surgery. Patients with better preoperative BCVA (p < 0.001), and those who underwent 25G PPV (p = 0.041) showed better visual outcomes. CONCLUSIONS: PPV is an effective technique for improving visual acuity in patients aged 85 years and older with vitreoretinal diseases. Visual outcomes were better when patients had a better preoperative visual acuity and underwent 25G PPV. Patients with a previous diagnosis of AMD or CKD, and those undergoing surgery for ocular trauma or RRD had worse visual outcomes.

Novel TEVAR technique for thoracic aortic aneurysm repair: A case report.

INTRODUCTION AND IMPORTANCE: A thoracic aortic aneurysm (TAA) is a life-threatening condition affecting 5-10 per 100,000 people per year. If not repaired, mortality rates are reported as high as 11.8 %, increasing to 97 %-100 % following a TAA rupture. Thoracic endovascular aortic repairs (TEVAR) are becoming more common, but currently face limitations due to complex vasculature. New techniques may provide a safer alternative. CASE PRESENTATION: 70-year-old male presenting with a history of hypertension, dyslipidemia, and previous replacement of ascending aorta and hemi arch with reimplantation of innominate artery done in 2020. A CT scan done during routine interval monitoring of previous TAA repair demonstrated a new aneurysm, which was confirmed with CT angiogram. A novel TEVAR technique was used for repair. The patient tolerated this procedure well and was discharged from the ICU after six days. CLINICAL DISCUSSION: Open procedures and hybrid techniques for TAA repair are not always suitable for high-risk patients. Alternative parallel grafting techniques have shown promising early results but still lack clinical support and long-term data. Several small-scale studies and case reports have demonstrated the use of in-situ laser fenestrations in various settings, but none have demonstrated the ability to extend the landing zone as far as zone 0 for repair of a Type B TAA. CONCLUSION: The use of this novel technique may be considered suitable in high-risk patients with various subtypes of TAAs not suitable for open repair. More cases and clinical trials are needed to compare risks and long-term results to more commonly performed procedures.

Republication of "First Metatarsophalangeal Joint Arthrodesis: Functional Outcomes Using 2 Different Fixation Techniques. Is More Expensive Better?"

Background: First metatarsophalangeal (MTP) joint arthrodesis can be fixed using either a dorsal plate or crossed screws. However, there is considerable difference in the cost of these implants, and it is not known if there is sufficient difference in outcome that might justify this cost difference. Our aim was to compare the functional results and patient satisfaction rates after first MTP joint arthrodesis in a group of patients using the same surgical technique except for the fixation devices. Methods: A prospective cohort of 27 patients who underwent first MTP joint fusion by the same surgeon using 2 crossed screws or a single screw with a dorsal plate was recruited over a 3-year period. Demographic information, patient satisfaction rates, complications, and union rates were evaluated. American Orthopaedic Foot & Ankle Society (AOFAS) and visual analog scale (VAS) scoring systems were used pre- and postoperatively to compare the functional outcomes. Thirty consecutive procedures (screws, n = 15; plate, n = 15) were performed. Age (55.8 ± 11.1 vs 63.3 ± 12.4 years for screws and plate respectively; P = .091) and female gender percentages (80% and 73%, P = .666) were similar between groups. Results: The overall union rate was 93% with no differences between groups. AOFAS and VAS scores improved significantly postoperatively for each technique, and no differences were found between the two in the improvement in AOFAS (42.4 ± 8.0 vs 44.3 ± 8.2, screws and plate respectively; P = .520) and VAS scores (66.0 ± 5.4 vs 69.0 ± 6.9;P = .195). The implant cost for screws was $40 and for dorsal plate, $328. Conclusions: First MTP joint fusion using either screws or plate fixation results in an improvement in AOFAS and VAS scores. Functional improvement and patient satisfaction did not differ between the 2 techniques, despite a considerable difference in cost between the two methods of fixation. Level of Evidence: Level III, prospective comparative study.

Effects of Foot Structure Type on Core Stability in University Athletes.

PURPOSE: This study assessed the impact of different types of medial foot arch on postural stability and core center of gravity muscle activity among collegiate athletes. METHODS: The study sample included 103 university-level athletes across various sports (soccer, rugby, basketball, volleyball, field tennis, table tennis, karate, and cheerleading) from the College of Magdalena (Colombia) who exhibited distinct types of medial foot arch: 32 high, 35 low, and 36 neutral arches. Surface electromyography (sEMG) was employed to assess conduction velocity, magnitude values, latency, and fatigue in focal muscles including the spinal erector (SE), internal oblique (IO), external oblique (EO), and rectus abdominis (AR), while measurements of static and dynamic postural control were also considered. Post hoc analysis was performed with Bonferroni correction for all electromyographically measured muscle groups, as well as for measurements of static and dynamic postural stability. Pearson's or Spearman's correlation tests were used to compare the different types of feet. RESULTS: There were no substantial differences observed between the distinct types of feet in terms of focal muscle activity, static stability, or dynamics. Even though the mean values indicated higher muscle activity and stability among those with high foot arches and lower values among those with low arches compared to the neutral foot type, this observed difference was deemed statistically insignificant. We also observed a positive correlation between internal oblique muscle activity and the average power of dynamic postural stability, which remained consistent across all foot types. Our findings indicate that static instability is directly correlated with dynamic instability in the anteroposterior direction, while a clear inverse relationship was established in the lateral direction upon examining the variable correlations. CONCLUSIONS: The presence of high or low foot arches did not significantly impact the activity of the muscles responsible for maintaining the body's center of gravity or postural stability among university-level athletes. This suggests the existence of neuromuscular compensation mechanisms that attempt to restore balance and compensate for any changes in postural stability caused by varying foot types. Through targeted training that emphasizes activation of the internal oblique muscle, athletes may see improved postural stability. Our findings indicate that static stabilization exercises can also prove beneficial in improving dynamic stability in the anteroposterior plane, while a more dynamic approach may be required to improve dynamic stability in the lateral plane.

Macular hole Delphi consensus statement (MHOST).

PURPOSE: To derive a Delphi method-based consensus for the surgical management of Full Thickness Macular Hole (FTMH) and Lamellar Macular Hole (LMH). METHODS: 37 expert VR surgeons from 21 mainly European countries participated in Delphi method-based questionnaire for diagnosis and treatment of FTMHs and LMHs. RESULTS: A total of 36 items were rated in round 1 by 37 participants, of which 10 items achieved consensus: intraoperative verification of PVD; clinical superiority of OCT-based FTMH classification; practical ineffectiveness of ocriplasmin; circular 360° ILM peeling for small macular holes; use of regular surgical technique for the size of the hole in concomitant retinal detachment; performing complete vitrectomy; SF6 gas as preferred tamponade; cataract surgery if crystalline lens is mildly/moderately opaque; removal of both ILM and LHEP in LMH surgery. In round 2, 18 items with moderate consensus (45-70% agreement) in round 1 were rated by 35 participants. Final consensus was reached in 35% of questions related to both diagnosis and surgical procedures. CONCLUSIONS: This Delphi study provides valuable information about the consensus/disagreement on different scenarios encountered during FTMH and LMH management as a guide tosurgical decision-making. High rate of disagreement and/or variable approaches still exist for treating such relatively common conditions.

A COVID-19 perspective of Vogt-Koyanagi-Harada disease.

Vogt-Koyanagi-Harada (VKH) disease, a bilateral granulomatous panuveitis associated with multisystem involvement, is a T-cell-mediated autoimmune disorder in which cytotoxic T-cell target melanocytes in genetically susceptible individuals. Recently, there has been an increase in literature on the new onset of uveitis and reactivation of previously diagnosed cases of uveitis following Covid-19 vaccinations. It has been postulated that Covid-19 vaccines can lead to an immunomodulatory change resulting in an autoimmune phenomenon in the recipients. VKH following COVID-19 infection was reported in four patients and a total of 46 patients developing VKH or VKH-like disease following COVID-19 vaccinations. There are reports of four patients who had been recovering or recovered from VKH after receiving the first dosage of the vaccine and developed worsening of ocular inflammation after receiving the second dose of the vaccine.

Changes in patterns of Early Mother-Child Interaction: A longitudinal study of the first 18 months of life.

OBJECTIVE: The main objective of the present longitudinal study is to describe the progression of early adult-child interactions between the first and second years of life. Changes identified in interactions are described, focusing on both the qualitative aspects of maternal responses, as well as maternal response latency to the child's behavior using a microanalytical methodology that collected data on maternal and child behavior in real-time without losing sight of the temporal dimension. PARTICIPANTS: This study examined 52 mother-child dyads from intact families that presented no psychological, social, or biological risk factors at 6, 12 and 18 months of age. INSTRUMENT: CITMI-R (early mother-child interaction coding system, revised edition) was used to assess early mother-infant interactions during free play sessions between mother and child the. RESULTS: The results indicate that some components of maternal sensitivity improve as children progress towards the second year of life, detecting an increase in sensitive maternal behavior and a decrease in intrusive behavior in the evolutive observed period; moreover, regarding latency of maternal response, we observed that mothers of older children give more time for their children to explore, which stimulates autonomy. Finally, the implication of these results for intervention directed to optimizing early adult-child interactions are addressed.

Multimodal Imaging Study of Patients With Vitamin A Deficiency Retinopathy.

OBJECTIVES: To describe multimodal imaging findings of vitamin A deficiency retinopathy. METHODS: A retrospective study of patients with serum retinol < 0.3 mg/L. Fundus color photos, spectral domain-optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) were reviewed and, when available, electrophysiological tests were analyzed. RESULTS: Forty-five eyes (63.9 ± 15.7 years) were included. Ultra-widefield fundus photography showed drusen-like deposits (53.3%) and macular retinal pigment epithelium (RPE) mottling (40%). The deposits were hypoautofluorescent, and a perifoveal hyperautofluorescent ring was present in 8.9%. By SD-OCT, the ellipsoid zone had an irregular appearance (100%) and conical deposits anterior to the RPE (33.3%). Electroretinogram (ERG) (66.7%) showed a decrease in b-wave in the scotopic registers, and microperimetry (4.4%) showed decreased foveal sensitivity. After vitamin A supplementation, SD-OCT and FAF showed resolution of all findings. Forty percent of eyes had restoration of the scotopic registers in ERG and improved macular sensitivity by microperimetry (4.4%). CONCLUSIONS: Vitamin A deficiency causes a mild cone dysfunction in addition to the more severe absent rod response. [Ophthalmic Surg Lasers Imaging Retina 2023;54:330-336.].

Dietary Nitrate Ingestion Does Not Improve Neuromuscular Performance in Male Sport Climbers.

Beetroot juice (BJ) is commonly used as an ergogenic aid in endurance and team sports, however, the effect of this supplement on climbing performance is barely studied. The purpose of the current study was to investigate the effect of acute BJ ingestion on neuromuscular and biochemical variables in amateur male sport climbers. Ten physically active sport climbers (28.8 ± 3.7 years) underwent a battery of neuromuscular tests consisting of the half crimp test, the pull-up to failure test, the isometric handgrip strength test, the countermovement jump (CMJ) and the squat jump (SJ). Participants performed the neuromuscular test battery twice in a cross-over design separated by 10 days, 150 min after having consumed either 70-mL of BJ (6.4 mmol NO3-) or a 70-mL placebo (0.0034 mmol NO3-). In addition, nitrate (NO3-) and nitrite (NO2-) saliva concentrations were analysed, and a side effect questionnaire related to ingestion was administrated. No differences were reported in particular neuromuscular variables measured such as the CMJ (p = 0.960; ES = 0.03), the SJ (p = 0.581; ES = -0.25), isometric handgrip strength (dominant/non dominant) (p = 0.459-0.447; ES = 0.34-0.35), the pull-up failure test (p = 0.272; ES = 0.51) or the maximal isometric half crimp test (p = 0.521-0.824; ES = 0.10-0.28). Salivary NO3- and NO2- increased significantly post BJ supplementation compared to the placebo (p < 0.001), while no side effects associated to ingestion were reported (p = 0.330-1.000) between conditions (BJ/placebo ingestion). Acute dietary nitrate supplementation (70-mL) did not produce any statistically significant improvement in neuromuscular performance or side effects in amateur sport climbers.

Pluronic F127 and P104 Polymeric Micelles as Efficient Nanocarriers for Loading and Release of Single and Dual Antineoplastic Drugs.

The potential application of biodegradable and biocompatible polymeric micelles formed by Pluronic F127 and P104 as nanocarriers of the antineoplastic drugs docetaxel (DOCE) and doxorubicin (DOXO) is presented in this work. The release profile was carried out under sink conditions at 37 °C and analyzed using the Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin diffusion models. The cell viability of HeLa cells was evaluated using the proliferation cell counting kit CCK-8 assay. The formed polymeric micelles solubilized significant amounts of DOCE and DOXO, and released them in a sustained manner for 48 h, with a release profile composed of an initial rapid release within the first 12 h followed by a much slower phase the end of the experiments. In addition, the release was faster under acidic conditions. The model that best fit the experimental data was the Korsmeyer-Peppas one and denoted a drug release dominated by Fickian diffusion. When HeLa cells were exposed for 48 h to DOXO and DOCE drugs loaded inside P104 and F127 micelles, they showed lower IC50 values than those reported by other researchers using polymeric nanoparticles, dendrimers or liposomes as alternative carriers, indicating that a lower drug concentration is needed to decrease cell viability by 50%.