Clinical Correlates of the PET-based Braak Staging Framework in Alzheimer's Disease.

In vivo Alzheimer's disease diagnosis and staging is traditionally based on clinical features. However, the agreement between clinical and pathological Alzheimer's disease diagnosis, whose diagnosis assessment includes amyloid and Braak histopathological tau staging, is not completely convergent. The development of positron emission tomography (PET) tracers targeting neurofibrillary tangles offers prospects for advancing the staging of Alzheimer's disease from both biological and clinical perspectives. Recent advances in radiochemistry made it possible to apply the postmortem Braak staging framework to tau-PET images obtained in vivo. Here, our aim is to provide a narrative review of the current literature on the relationship between Alzheimer's disease clinical features and the PET-based Braak staging framework. Overall, the available studies support the stepwise increase in disease severity following the advance of PET-based Braak stages, with later stages being associated with worse cognitive and clinical symptoms. In line with this, there is a trend for unimpaired cognition, mild cognitive impairment, and Alzheimer's disease dementia to be compatible with early, intermediate, and late patterns of tau deposition based on PET-based Braak stages. Moreover, neuropsychiatric symptom severity seems to be linked to the extent of tau-PET signal across Braak areas. In sum, this framework seems to correspond well with the clinical progression of Alzheimer's disease, which is an indication of its potential utility in research and clinical practice, especially for detecting preclinical tau levels in individuals without symptoms. However, further research is needed to improve the generalizability of these findings and to better understand the applications of this staging framework.

Sex dimorphism of weight and length at birth: evidence based on disorders of sex development.

BACKGROUND: Males have higher weight and length at birth than females. AIM: To verify the influence of the Y chromosome and the action of intrauterine androgens on weight and length at birth of children with Disorders of Sex Development (DSD). SUBJECTS AND METHODS: A cross-sectional and retrospective study. Patients with Turner syndrome (TS), complete (XX and XY), mixed (45,X/46,XY) and partial (XY) gonadal dysgenesis (GD), complete (CAIS) and partial (PAIS) androgen insensitivity syndromes and XX and XY congenital adrenal hyperplasia (CAH) were included. Weight and length at birth were evaluated. RESULTS: Weight and length at birth were lower in TS and mixed GD when compared to XY and XX DSD cases. In turn, patients with increased androgen action (117 cases) had higher weight and length at birth when compared to those with absent (108 cases) and decreased (68 cases) production/action. In birthweight, there was a negative influence of the 45,X/46,XY karyotype and a positive influence of increased androgen and gestational age. In birth length, there was a negative influence of the 45,X and 45,X/46,XY karyotypes and also a positive influence of increased androgen and gestational age. CONCLUSIONS: The sex dimorphism of weight and length at birth could possibly be influenced by intrauterine androgenic action.

Corneal haze post photorefractive keratectomy.

Corneal haze represents subepithelial corneal fibrosis, a manifestation of a pathological healing process. It occurs as a result of an epithelial-stromal lesion involving a break in the epithelial barrier. It is an inflammatory response that involves the migration, multiplication and differentiation of keratocytes into mature myofibroblasts, causing loss of corneal transparency. Although it is a transient phenomenon, this complication is feared following refractive photokeratectomy (PRK), because it can cause alterations in the quality of vision, refractive regression and decreased visual acuity. The severity of these symptoms is correlated with the severity of the corneal haze, which can be assessed clinically or by objective means such as corneal densitometry measurement. The frequency and severity of corneal haze increase with the depth of photoablation in PRK and are therefore increased during the treatment of severe ametropia. Considering that no consensus exists, the application of mitomycin C (MMC) intraoperatively and topical corticosteroids postoperatively are conventionally used to inhibit collagen synthesis, sometimes in combination with various protocols depending on the center or surgeon. This review of the literature reports the current knowledge on corneal haze, in order to better understand it and optimise its prevention in the context of a decreased MMC supply, which has occurred in the past and could recur in the future.

Eyelid Chemical Burns: A Multidisciplinary And Challenging Approach.

During second- and third-degree eyelid sulfuric acid burns, many surgeons prefer to wait until primary wound separation occurs before grafting. However, this approach may miss the chance to recover the eyelids and can cause ectropion, resulting in delayed eyeball healing with exposure keratitis. We propose that early eyelid release and grafting makes a significant difference in long-term outcomes and improves eyeball healing. Here, we present the case of a woman who presented second- and third-degree burns of the eyelids secondary to physical domestic assault with acid, who had an early surgical management with a full-thickness skin graft. Ten days after surgery, we found that the graft had survived totally, and the donor site of the right arm had already healed. Eyelids were successfully grafted and the functions of both eyelids were well recovered, allowing complete cover of the eyeball. Two months after surgery, functional and cosmetic results were satisfying, with no postoperative lagophthalmos or difficulties with exposure-related problems. Case reports of eyelid chemical burns are very few. No specific and codified management of eyelid chemical burns was found in the literature search. This case report demonstrated that a multidisciplinary approach led by both ophthalmologists and plastic surgeons must be decided early (<6h) in order to achieve synergistic and coordinated management between the eye and the eyelid. There is a significant improvement in ocular healing with early excision and grafting of eyelids after sulfuric acid burn.

En cas de brûlure du 2ème ou du 3ème degré des paupières par acide sulfurique, de nombreux chirurgiens préfèrent attendre la séparation spontanée de l'escarre avant de greffer. Cette stratégie comporte le risque d'une cicatrisation défectueuse source d'ectropion, d'occlusion incomplète et de kératite. Nous conjecturons qu'une excision-greffe précoce améliore le pronostic à long terme de ce type de brûlure. Nous présentons le cas d'une femme victime d'une agression intra-familiale à l'acide sulfurique, souffrant de brûlure des 2ème et 3ème degrés des paupières traitée par excision-greffe de peau totale précoce. À J10, la greffe était totalement intégrée et le site donneur (bras droit) était cicatrisé. La fonction palpébrale était normale et l'occlusion oculaire complète. Ces bons résultats persistaient à 2 mois, sans lagophtalmie ni défaut d'occlusion, avec un aspect esthétique correct. Les rapports de brûlures chimiques des paupières sont peu fréquents et il nous n'avons pas trouvé de protocole dans la littérature. Ce cas clinique illustre la nécessité d'une analyse précoce (dans les 6h) par ophtalmologiste et plasticien afin de définir une stratégie coordonnée vis à vis du globe oculaire et de la paupière. L'excision-greffe précoce améliore la pronostic oculaire après brûlure par acide sulfurique.

[Same-eye comparison of pupillary dilation with an intraoperative standardized intracameral combination of mydriatics (Mydrane®) versus a preoperative ophthalmic (Mydriasert®) in standard cataract surgery in non-diabetic patients (French translation of the article)]. / Comparaison intra-individuelle de la dilatation pupillaire par une solution intracamérulaire standardisée combinée de mydriatiques (Mydrane®) en peropératoire versus un insert ophtalmique (Mydriasert®) en préopératoire dans la chirurgie de la cataracte standard de patients non diabétiques.

INTRODUCTION: Cataract surgery is the most commonly performed surgery in the world, and its success depends in part on the quality of mydriasis. PURPOSE: To compare, for the same eye, the pupillary dilation obtained with Mydrane® (standardized intracameral solution of 0.02% tropicamide, combined with 0.31% phenylephrine and 1% lidocaine) intraoperatively versus Mydriasert® (0.28mg tropicamide insert and 5.4mg phenylephrine) with a contact time between 45 and 60 minutes in the preoperative period. METHODS: Single center prospective study from November 2016 to January 2018 at the Laveran Army Instructional Hospital in Marseille. Patients referred for surgery were dilated at the preoperative consultation with Mydriasert®. The pupillary diameter after 45-60 minutes of contact with the insert was manually measured, by two different examiners, through the "iris image" tab of the Pentacam® elevation topography. Patients were dilated on the day of their cataract surgery with 0.2cc of Mydrane® injected in the anterior chamber through a paracentesis. Thirty seconds later, prior to injection of viscoelastic, an eye photograph was taken by screen capture. The pupillary diameter was evaluated by two different examiners with to the Piximeter 5.9 metrology software. The difference in pupil dilation between Mydriasert® and Mydrane® was tested with the paired series Student t-test. RESULTS: In total, 111 eyes of 82 patients were included. Mydriasert® achieved a mean pupillary dilation of 7.21±0.79mm. The mydriasis obtained with Mydrane® averaged 6.35±0.8mm. This difference of 0.86mm was statistically significant (P<0.001) with a confidence interval of 95% [-0.97; -0.74]. CONCLUSION: On average, Mydrane® dilates the pupil less than Mydriasert®. However, the mydriasis obtained with Mydrane® remains comfortable for the performance of the capsulorhexis. It helps save preoperative time and affords additional anesthetic to the cataract surgery. Nevertheless, the use of Mydriasert® is beneficial when extra mydriasis is required.

Same-eye comparison of pupillary dilation with an intraoperative standardized intracameral combination of mydriatics (Mydrane®) versus a preoperative ophthalmic (Mydriasert®) in standard cataract surgery in non-diabetic patients.

INTRODUCTION: Cataract surgery is the most commonly performed surgery in the world, and its success depends in part on the quality of mydriasis. PURPOSE: To compare, for the same eye, the pupillary dilation obtained with Mydrane® (standardized intracameral solution of 0.02% tropicamide, combined with 0.31% phenylephrine and 1% lidocaine) intraoperatively versus Mydriasert® (0.28mg tropicamide insert and 5.4mg phenylephrine) with a contact time between 45 and 60 minutes in the preoperative period. METHODS: Single center prospective study from November 2016 to January 2018 at the Laveran Army Instructional Hospital in Marseille. Patients referred for surgery were dilated at the preoperative consultation with Mydriasert®. The pupillary diameter after 45-60 minutes of contact with the insert was manually measured, by two different examiners, through the "iris image" tab of the Pentacam® elevation topography. Patients were dilated on the day of their cataract surgery with 0.2cc of Mydrane® injected in the anterior chamber through a paracentesis. Thirty seconds later, prior to injection of viscoelastic, an eye photograph was taken by screen capture. The pupillary diameter was evaluated by two different examiners with to the Piximeter 5.9 metrology software. The difference in pupil dilation between Mydriasert® and Mydrane® was tested with the paired series Student t-test. RESULTS: A hundred and eleven eyes of 82 patients were included. Mydriasert® achieved a mean pupillary dilation of 7.21±0.79mm. The mydriasis obtained with Mydrane® averaged 6.35±0.8mm. This difference of 0.86mm was statistically significant (P<0.001) with a confidence interval of 95% [-0.97; -0.74]. CONCLUSION: On average, Mydrane® dilates the pupil less than Mydriasert®. However, the mydriasis obtained with Mydrane® remains comfortable for the performance of the capsulorhexis. It helps save preoperative time and affords additional anesthetic to the cataract surgery. Nevertheless, the use of Mydriasert® is beneficial when extra mydriasis is required.

Estrogen and phenol red free medium for osteoblast culture: study of the mineralization ability.

To design an estrogen and phenol red free medium for cell culture and check its effectiveness and safety on osteoblast growth it is necessary to maintain the estrogen receptors free for tests. For this purpose, we tested some modifications of the traditional culture media: estrogen depleted fetal bovine serum; estrogen charcoal stripped fetal bovine serum and phenol red free α-MEM. The aim of this work is to examine the effects of its depletion in the proliferation, differentiation, and toxicity of mesenchymal stromal cells differentiated into osteoblasts to obtain an effective interference free culture medium for in vitro studies, focused on non-previously studied estrogen receptors. We performed viability tests using the following techniques: MTT, alkaline phosphatase specific activity, formation of mineralized matrix by Alizarin technique and analysis of SEM/EDX of mineralized nodules. The results showed that the culture media with estrogen free α-MEM + phenol red free α-MEM did not impact viability, alkaline phosphatase activity and mineralization of the osteoblasts culture compared to control. In addition, its nodules possess Ca/P ratio similar to hydroxyapatite nodules on the 14th and 21st day. In conclusion, the modified culture medium with phenol red free α-MEM with estrogen depleted fetal bovine serum can be safely used in experiments where the estrogen receptors need to be free.

Evaluation of new alternatives in wastewater treatment plants based on dynamic modelling and life cycle assessment (DM-LCA).

With a view to quantifying the energy and environmental advantages of Urine Source-Separation (USS) combined with different treatment processes, five wastewater treatment plant (WWTP) scenarios were compared to a reference scenario using Dynamic Modelling (DM) and Life Cycle Assessment (LCA), and an integrated DM-LCA framework was thus developed. Dynamic simulations were carried out in BioWin(®) in order to obtain a realistic evaluation of the dynamic behaviour and performance of plants under perturbation. LCA calculations were performed within Umberto(®) using the Ecoinvent database. A Python™ interface was used to integrate and convert simulation data and to introduce them into Umberto(®) to achieve a complete LCA evaluation comprising foreground and background processes. Comparisons between steady-state and dynamic simulations revealed the importance of considering dynamic aspects such as nutrient and flow peaks. The results of the evaluation highlighted the potential of the USS scenario for nutrient recovery whereas the Enhanced Primary Clarification (EPC) scenario gave increased biogas production and also notably decreased aeration consumption, leading to a positive energy balance. Both USS and EPC scenarios also showed increased stability of plant operation, with smaller daily averages of total nitrogen and phosphorus. In this context, USS and EPC results demonstrated that the coupled USS + EPC scenario and its combinations with agricultural spreading of N-rich effluent and nitritation/anaerobic deammonification could present an energy-positive balance with respectively 27% and 33% lower energy requirements and an increase in biogas production of 23%, compared to the reference scenario. The coupled scenarios also presented lesser environmental impacts (reduction of 31% and 39% in total endpoint impacts) along with effluent quality well within the specified limits. The marked environmental performance (reduction of global warming) when nitrogen is used in agriculture shows the importance of future research on sustainable solutions for nitrogen recovery. The contribution analysis of midpoint impacts also showed hotspots that it will be important to optimize further, such as plant infrastructure and direct N2O emissions.

[Multiple intracranial epidermoid cysts: Case report].

Epidermoid cyst is a benign and rare tumor, that evolves slowly. We describe the case of a 55 years-old woman, who came to our consultation for atypical trigeminal neuralgia of left V1 and V2 nerves. Brain MRI found two tumors: T1W hypointense with no appreciable enhancement after gadolinium injection and T2W and diffusion hyperintense. This last feature was in favour of an epidermoid cyst, but the multiplicity of cerebral lesions was definitely not in favor of such a diagnos­tic. They were located behind the right eye and in the left Meckel's cave (trigeminal cave). The surgical strategy consis­ted in removal the retro orbital tumor witch was the most acces­si­ble of both the diagnostic of epidermoid cyst was retaned thanks to the anatomopathology report. As these lesions had the exact same characteristics, we concluded that they were simi­lar. The second epidermoid cyst was not removed because of surgical risk, its benign nature and low evolutionary potential.

High-circulating leptin levels are associated with increased blood pressure in uncontrolled resistant hypertension.

Leptin and aldosterone have been associated with the pathophysiological mechanisms of hypertension. However, despite studies showing the association of leptin with intima-media thickness, arterial distensibility and sympathetic nerve activation, the relationship between leptin and blood pressure (BP) in resistant hypertension (RHTN) is unknown. We aimed to assess the correlation of plasma leptin and aldosterone levels with BP in uncontrolled controlled RHTN (UCRHTN) and CRHTN patients. Plasma leptin and aldosterone levels, office BP, ambulatory BP monitoring and heart rate were measured in 41 UCRHTN, 39 CRHTN and 31 well-controlled HTN patients. No differences were observed between the three groups regarding gender, body mass index and age. The UCRHTN group had increased leptin when compared with CRHTN and well-controlled HTN patients (38.2±21.4, 19.6±8.7 and 20.94±13.9 ng ml(-1), respectively; P<0.05). Aldosterone levels values were also statistically different when comparing RHTN, CRHTN and well-controlled HTN patients (9.6±3.8, 8.1±5.0 and 8.0±4.7 ng dl(-1), respectively; P<0.05). As expected, UCRHTN patients had higher heart rate values compared with CRHTN and well-controlled HTN patients (86.2±7.2, 83.5±6.7 and 83.4±8.5, respectively; P<0.05). Plasma leptin positively correlated with systolic (SBP) and diastolic BP (DBP), and aldosterone (r=0.43, 0.35 and 0.47, respectively; all P<0.05) in UCRHTN, but neither in the CRHTN nor in the HTN group. Simple linear regression showed that SBP, DBP and aldosterone may be predicted by leptin (r(2)=0.16, 0.15 and 0.19, respectively; all P<0.05) only in the UCRHTN subgroup. In conclusion, UCRHTN patients have higher circulating leptin levels associated with increased plasma aldosterone and BP levels when compared with CRHTN and HTN subjects.

OCT4 immunohistochemistry may be necessary to identify the real risk of gonadal tumors in patients with Turner syndrome and Y chromosome sequences.

BACKGROUND: The aim of this study was to investigate the frequency of gonadal tumors among patients with Turner syndrome (TS) carrying Y-derivative sequences in their chromosomal constitution. METHODS: Six out of 260 patients with TS were selected based on mosaicism of the entire Y chromosome; 10 were included because Y-derivative sequences have been detected by PCR with specific oligonucleotides (sex-determining region on the Y, testis specific-protein, Y and DYZ3) and further confirmed by FISH. The 16 patients were subjected to bilateral gonadectomy at ages varying from 8.7 to 18.2 years. Both histopathological investigation with hematoxylin and eosin (H&E) and immunohistochemical analysis with anti-octamer-binding transcription factor 4 (OCT4) antibody were performed. RESULTS: Gonadal neoplasia was not detected in any of the 32 gonads evaluated by H&E; however, four gonads (12%) from three patients (19%) had positive OCT4 staining in 50-80% of nuclei, suggesting the existence of germ cell tumors (gonadoblastoma or in situ carcinoma). CONCLUSIONS: Evaluation of the real risk of development of gonadal tumors in TS patients with Y-derivative sequences in their chromosomal constitution may require a specific histopathological study, such as immunohistochemistry with OCT4.