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Hypomyelinating leukodystrophies (HLD) are a group of heterogeneous genetic disorders characterized by a deficit in myelin deposition during brain development. Specifically, 4H-Leukodystrophy is a recessive disease due to biallelic mutations in the POLR3A gene, which encodes one of the subunits forming the catalytic core of RNA polymerase III (PolIII). The disease also presents non-neurological signs such as hypodontia and hypogonadotropic hypogonadism. Here, we report the generation of a human induced pluripotent stem cell (hiPSC) line from fibroblasts of the first identified carrier of the biallelic POLR3A variants c.1802 T > A and c.4072G > A.

Introduction: Intentional multiple drugs overdose is an often-encountered method of self-harm in adolescence. Treatments include supportive therapy, antidotes (when available) and decontamination techniques with the aim of reducing drugs absorption by the gastrointestinal system to minimize toxicity. Nevertheless, the decontamination techniques currently used, such as gastric lavage (GL), activated charcoal or whole-bowel irrigation, have a questionable effectiveness. Endoscopic gastric decontamination (EGD) treatment for massive ingestion of drugs or formation of pharmacobezoars is currently described only in anecdotal cases. Here we describe the management of an intentional drug overdose in an adolescent patient treated with EGD and the effects of this therapy on drugs pharmacokinetics. Case report: A 15-year-old boy was admitted in an unconscious state (Glasgow Coma Scale: 7–8) to the pediatric intensive care unit after assuming an unspecified amount of quetiapine, aspirin, bisoprolol, fluoxetine, furosemide, alprazolam, and pregabalin pills. Rapid sequence intubation was immediately performed and then the patient was treated with symptomatic therapy and GL with minimal removal of gastric material. Accounting for the type of drugs, the time elapsed from oral assumption and the unknown quantity assumed, EGD was attempted with aim of removing potential aggregate of the drugs. Serial blood samples were taken before and after EGD to measure the plasma level of the drugs. A pharmacobezoar was found and was immediately removed with EGD. The results of the drug monitoring showed that quetiapine exceeded the toxic level reported in literature indicating that it may have been the drug assumed in higher quantity by our patient. PICU stay was uneventful, and the patient was transferred to the psychiatric ward after extubation. Discussion: Our case shows how GL is not effective in mitigating multidrug absorption especially drugs potentially inducing pharmacobezoars. Furthermore, based on our plasma drug monitoring, we believe that early EGD should be considered in all cases of massive pill intake, prolonged release drugs that can form pharmacobezoars or in cases where a life-threatening dose cannot be excluded.

Background: After an initial Takotsubo syndrome (TTS) event, there is growing recognition of adverse long-term outcomes, including recurrent TTS events. Recurrent events have been incompletely evaluated. Objectives: The objective of this study was to characterize recurrent TTS events and evaluate variables associated with recurrence. Methods: We studied 88 consecutive participants in the Cedars-Sinai Smidt Heart Institute Takotsubo Registry, an observational registry collecting retrospective and prospective data in TTS survivors. Detailed medical records are adjudicated. Standardized psychosocial questionnaires are administered remotely. Results: Of 88 participants with adjudicated TTS, 15 (17%) experienced at least 1 recurrent TTS event (median 3.30 years to first recurrent event, range 0.13-18.56 years). In 9 of these 15 participants, there were different patterns of wall motion abnormalities observed between events. The recurrence-free survival significantly differed based on the pattern of wall motion abnormalities at the index TTS event. Clinical, electrocardiographic, echocardiographic, and invasive data obtained at the index TTS event were similar between participants who went on to have at least 1 recurrent event and those who did not. Conclusions: Recurrent TTS episodes occurred in a significant proportion of cases, a median of 3.30 years after the index event. The recurrent episodes often had distinct triggers and different wall motion abnormalities compared to the index event. The wall motion pattern at the index event impacted the recurrence-free survival, though confirmatory studies are needed. TTS participants had a high rate of adverse psychosocial stress characteristics based on detailed questionnaires. (The Cedars-Sinai Smidt Heart Institute Takotsubo Registry & Proteomic Study; NCT03910569)

Emotional dysfunctions in Parkinson's disease (PD) remain a controversial issue. While previous investigations showed compromised recognition of expressive faces in PD, no studies evaluated potential deficits in recognizing the emotional valence of affective scenes. This study aimed to investigate both facial emotion recognition performance and the ability to judge affective scenes in PD patients.Forty PD patients (mean age ± SD: 64.50 ± 8.19 years; 27 men) and forty healthy subjects (64.95 ± 8.25 years; 27 men) were included. Exclusion criteria were previous psychiatric disorders, previous Deep Brain Stimulation, and cognitive impairment. Participants were evaluated through the Ekman 60-Faces test and the International Affective Picture System. The accuracy in recognizing the emotional valence of facial expressions and affective scenes was compared between groups using linear mixed models. Pearson's correlation was performed to test the association between accuracy measures.The groups did not differ in sex, age, education, and Mini-Mental State Examination scores. Patients showed a lower recognition accuracy of facial expressions (68.54 % ± 15.83 %) than healthy participants (78.67 % ± 12.04 %; p

This case report investigates the potential use of metabolism as a sensitive biomarker in monitoring the effectiveness of anti-amyloid therapy in a patient with mild cognitive impairment due to early Alzheimer's disease. The study centers around a 74-year-old male patient treated with aducanumab, a monoclonal antibody developed for anti-amyloid therapy. Alongside an expected decline in cerebral amyloid monitored using PET amyloid tracers, we observed significant improvements in the patient's brain metabolic activity, measured via 18-fluorodeoxyglucose positron emission tomography (FDG PET). Despite limitations posed by the single-patient case study, the findings invite further research and consider the utilization of FDG PET as a surrogate for clinically meaningful changes in the treatment of early Alzheimer's disease. These findings suggest the potential for more personalized and effective therapeutic interventions.

Purpose: To report the efficacy and safety of navigated 577nm yellow subthreshold micropulse laser (YSML) treatment in a case of refractory cystoid macular edema (CME) following combined phaco-vitrectomy for rhegmatogenous retinal detachment (RRD). Observations: A 69-year-old male patient complained a slow and progressive visual loss in the right eye (RE) since two months. A complete ophthalmological evaluation was performed. Best corrected visual acuity (BCVA) was hand motion and slit lamp examination revealed a nuclear cataract and a total macula-off RRD in the RE. Patient underwent a combined phaco +25 gauge pars plana vitrectomy (PPV) with 5000 cSt silicon oil (SO) tamponade. At the 3-month follow up BCVA was 20/250, retina was completely flat but a macular proliferative vitreoretinopathy (PVR) was detected with swept source optical coherence tomography (SS-OCT) and a second 23 G PPV with PVR peeling and SO removal was performed. At 1 month visit from the second surgery retina was flat and BCVA was 20/200 due to a persistent CME. Oral carbonic anhydrase inhibitors and topical steroids were administered for 2 months without any improvements. At this point, YSML was applied with a macular grid pattern and at three months follow up visit SS-OCT showed a complete resolution of CME, BCVA was 20/100 and these anatomical and functional outcomes were maintained at 6 months follow-up. Conclusions and importance: YSML treatment may be considered a safe and effective treatment strategy for the management of refractory CME following complex RRD surgery cases.

Summary: Background: Major depressive disorder (MDD) is prevalent and disabling among older adults. Standing on its tolerability profile, vortioxetine might be a promising alternative to selective serotonin reuptake inhibitors (SSRIs) in such a vulnerable population. Methods: We conducted a randomised, assessor- and statistician-blinded, superiority trial including older adults with MDD. The study was conducted between 02/02/2019 and 02/22/2023 in 11 Italian Psychiatric Services. Participants were randomised to vortioxetine or one of the SSRIs, selected according to common practice. Treatment discontinuation due to adverse events after six months was the primary outcome, for which we aimed to detect a 12% difference in favour of vortioxetine. The study was registered in the online repository clinicaltrials.gov (NCT03779789). Findings: The intention-to-treat population included 179 individuals randomised to vortioxetine and 178 to SSRIs. Mean age was 73.7 years (standard deviation 6.1), and 264 participants (69%) were female. Of those on vortioxetine, 78 (44%) discontinued the treatment due to adverse events at six months, compared to 59 (33%) of those on SSRIs (odds ratio 1.56; 95% confidence interval 1.01–2.39). Adjusted and per-protocol analyses confirmed point estimates in favour of SSRIs, but without a significant difference. With the exception of the unadjusted survival analysis showing SSRIs to outperform vortioxetine, secondary outcomes provided results consistent with a lack of substantial safety and tolerability differences between the two arms. Overall, no significant differences emerged in terms of response rates, depressive symptoms and quality of life, while SSRIs outperformed vortioxetine in terms of cognitive performance. Interpretation: As opposed to what was previously hypothesised, vortioxetine did not show a better tolerability profile compared to SSRIs in older adults with MDD in this study. Additionally, hypothetical advantages of vortioxetine on depression-related cognitive symptoms might be questioned. The study's statistical power and highly pragmatic design allow for generalisability to real-world practice. Funding: The study was funded by the Italian Medicines Agency within the “2016 Call for Independent Drug Research”.

This paper presents the properties of alkali-activated slag (AAS) mortar additivated with a superabsorbent polymer (SAP) to improve its mechanical and durability properties. The effect of different dosages of SAP (0.0–0.3% with respect to the blast furnace slag weight) and different extra water additions on setting time, autogenous shrinkage, compressive strength, water permeability, frost resistance, heat of hydration, and porosity is presented and discussed. The results highlight the beneficial effect of adding SAP on the mechanical and durability properties of the proposed mixtures. Only at higher percentages of SAP and additional water occur performance drops due to excessive macro-porosity of the system. It is interesting to point out that, in contrast, shrinkage always decreases as the percentages of SAP addition and additional water increase, although it cannot be completely eliminated. Experimental evidence also highlights that significant benefits can be gained from using this material in harsh environments.

Introduction: Heart failure (HF) is a frequent cause of readmissions. Despite caring for underresourced patients and dependence on government funding, safety net hospitals frequently incur penalties for failing to meet pay-for-performance readmission metrics. Limited research exists on the causes of HF readmissions in safety net hospitals. Therefore, we sought to investigate predictors of 30-day all-cause readmission in HF patients in the safety net setting. Methods: We performed a retrospective chart review of patients admitted for HF from October 2018 to April 2019. We extracted data on demographics and medical comorbidities and performed patient-specific review of social determinants and mental health in 4 domains: race/ethnicity, housing status, substance use, and mental illness. Multivariable Poisson regression modeling was employed to evaluate associations with 30-day all-cause readmission. Results: The study population included 290 patients, among whom the mean age was 59 years and 71% (n = 207) were male; 42% (120) were Black/African American (AA), 22% (64) were Hispanic/Latino, and 96% (278) had public insurance; 28% (79) were not housed, 19% (56) had a diagnosis of mental illness, and active substance use was common. The 30-day readmission rate was 25.5% (n = 88). Factors that were associated with increased risk of readmission included self-identifying as Black/AA (relative risk 2.28, 95% confidence interval 1.00-5.20) or Hispanic/Latino (2.53, 1.07-6.00), experiencing homelessness (2.07, 1.21-3.56), living in a shelter (3.20, 1.27-8.02), or intravenous drug use (IVDU) (2.00, 1.08-3.70). Conclusion: Race/ethnicity, housing status, and substance use were associated with increased risk of 30-day all-cause readmission in HF patients in a safety net hospital. In contrast to prior studies, medical comorbidities were not associated with increased risk of readmission.

Introdução/objetivos: O monitoramento da Síndrome Respiratória Aguda Grave (SRAG) foi adotado no Brasil desde 2009. Durante a pandemia de COVID-19 houve um cenário disruptivo epidemiológico no Brasil. Objetivos: avaliar os atributos de qualidade da vigilância de síndrome respiratória aguda grave (SRAG) de 2015 a 2021 em adultos, em hospital de referência terciária no sudeste brasileiro em dois períodos distintos. Métodos: estudo de série temporal compreendendo coorte de casos notificados de SRAG de base hospitalar. Foram incluídos pacientes adultos com idade maior ou igual a 18 anos notificados como SRAG pelo Núcleo de Vigilância Epidemiológica do Hospital de Clínicas da UNICAMP no período de janeiro de 2015 a dezembro de 2021. Utilizou-se o modelo de série temporal SARIMAX. Resultados: Foram analisados 1.496 casos do período pré-pandêmico e 1.199 casos do período pandêmico. Identificou-se uma média anual de SRAG de 299 e 599 casos, respectivamente, com aumento expressivo na 11ª SE de 2020 até meados da 30ª SE de 2021. Em 2020 e 2021, mais de 50% dos casos de SRAG foram definidos por infecção pelo Sars-Cov-2, principalmente por critério laboratorial e menos de 20% de SRAG no período pré-pandêmico definido como infecção pelo vírus Influenza. Dentre os atributos de oportunidade, o intervalo entre os primeiros sintomas e a internação foi significativamente menor no período pandêmico, correspondendo a uma mediana de seis dias, enquanto no período pré-pandêmico, tais valores corresponderam a uma mediana de 14 dias. O tempo de permanência na UTI foi maior no período pandêmico, com mediana de 12 dias em comparação a sete dias do período pré-pandêmico. O intervalo entre a internação e o desfecho clínico foi significativamente menor no período pandêmico, com mediana de 11 dias em comparação aos 36 dias do período pré-pandêmico. A evolução da doença se mostrou significativamente mais rápida na infecção por Sars-Cov-2 (p < 0,0001), com taxa de letalidade de 35,4%. Conclusões: O sistema de vigilância sindrômica apresenta qualidade e utilidade para a monitorização das síndromes respiratórias tanto em situações endêmicas como epidêmicas e por patógenos conhecidos ou emergentes. Entretanto, há a necessidade de qualificação do diagnóstico etiológico.

Introduction: The current study aims at describing a sample of adolescents admitted to a tertiary referral pediatric hospital for drug self-poisoning and to identify variables that could explain and predict a higher severity of intoxication. Methods: We retrospectively reviewed the cases of drug self-poisoning in adolescents admitted to the Bambino Gesù Children’s Hospital between January 2014 and June 2022 requiring consultation by the local Pediatric Poison Control Center (PPCC). We reported the type and class of drug ingested and correlated the clinical characteristics of the patients with their Poison Severity Score. Results: The data of 267 patients were reported. Most patients were female (85.8 %), with a median age of 15.8 years at presentation. Half of the patients were symptomatic at admission (44.2 %), and most had at least one psychiatric comorbidity (71.1 %). Most patients were hospitalized (79.6 %), 16.6 % of cases required antidote administration and a minority required intensive care. Most patients received a PSS score of 0 (59.6 %). The most frequently ingested drug was acetaminophen (28.1 %) followed by ibuprofen (10.1 %) and aripiprazole (10.1 %). Antipsychotics as a class were the most abused drugs (33.1 %). The correlation of clinical variables with the PSS showed that older and male patients were more prone to be severely intoxicated. Conclusions: This single-center study identifies the most commonly ingested drugs in a large sample of adolescents with voluntary drug self-poisoning, also showing that older and male patients are more susceptible to severe intoxication.

Circadian rhythm impairment may play a role in Parkinson's disease (PD) pathophysiology. Recent literature associated circadian rhythm features to the risk of developing Parkinson and to its progression through stages. The association between the chronotype and the phenotype should be verified on a clinical and biological point of view. Herein we investigate the chronotype of a sample of 50 PD patients with the Morningness Eveningness Questionnaire and monitor their daily activity with a motion sensor embedded in a smartphone. Fibroblasts were collected from PD patients (n = 5) and from sex/age matched controls (n = 3) and tested for the circadian expression of clock genes (CLOCK, BMAL1, PER1, CRY1), and for cell morphology, proliferation, and death. Our results show an association between the chronotype and the PD phenotype. The most representative clinical chronotypes were “moderate morning” (56%), the “intermediate” (24%) and, in a minor part, the “definite morning” (16%). They differed for axial motor impairment, presence of motor fluctuations and quality of life (p

Background: Autoimmune blistering disorders (AIBDs) are rare, potentially life-threatening conditions often requiring immunosuppression. Throughout the SARS-CoV-2 pandemic, infection risk and mortality in patients with AIBDs are unknown. Objective: We report the outcomes of SARS-CoV-2 infections in patients with AIBDs and determined if patients on rituximab have an increased risk of SARS-CoV-2 infection. Methods: We examined clinical outcomes in 10 patients with AIBDs who developed SARS-CoV-2 infections at an American hospital. We performed a retrospective analysis of 132 patients with AIBDs enrolled in a clinical trial. Results: Patients with severe SARS-CoV-2 (n = 4) or death (n = 2) trended to be older. These patients had higher mortality than the national average (20% vs 1.6%). Our cohort included 52 patients with a history of rituximab treatment, 35 of whom were immunosuppressed by rituximab during the pandemic, and 45 patients never treated with rituximab. We found no difference between the rates of SARS-CoV-2 positivity in patients with AIBDs immunosuppressed by rituximab and those not on rituximab (9.1% vs 12.1%). Limitations: Testing for SARS-CoV-2 was performed on demand rather than surveillance. Overall transmission varied over time, and outcomes depended on accepted treatments. The small sample size of our cohort limits the generalizability of our results. Conclusion: This study suggests that rituximab does not increase the risk of SARS-CoV-2 test positivity in patients with AIBDs. However, these results should be interpreted with caution due to our relatively small sample size.

The early differential diagnosis of Parkinson's disease (PD) and atypical Parkinsonian syndromes (APS), including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), is challenging because of an overlap of clinical features and the lack of reliable biomarkers. Neural-derived extracellular vesicles (NDEVs) isolated from blood provide a window into the brain's biochemistry and may assist in distinguishing between PD and APS. We verified in a case-control study whether oligomeric α-Synuclein and Tau aggregates isolated from NDEVs could allow the differential diagnosis of these conditions.Blood sampling and clinical data, including disease duration, motor severity, global cognition, and levodopa equivalent daily dose (LEDD), were collected from patients with a diagnosis of either PD (n = 70), PSP (n = 21), or CBD (n = 19). NDEVs were isolated from serum by immunocapture using an antibody against the neuronal surface marker L1CAM; oligomeric α-Synuclein and aggregated Tau were measured by ELISA.NDEVs analyses showed that oligomeric α-Synuclein is significantly augmented in PD compared to APS, whereas Tau aggregates are significantly increased in APS compared to PD (p

The acid-base goal of intermittent hemodialysis is to replenish buffers consumed by endogenous acid production and expansion acidosis in the period between treatments. The amount of bicarbonate needed to achieve this goal has traditionally been determined empirically with a goal of obtaining a reasonable subsequent predialysis blood bicarbonate concentration ([HCO3-]). This approach has led to very disparate hemodialysis prescriptions around the world. The bath [HCO3-] usually chosen in the United States and Europe causes a rapid increase in blood [HCO3-] in the first 1-2 hours of treatment, with little change thereafter. New studies show that this abrupt increase in blood [HCO3-] elicits a buffer response that removes more bicarbonate from the extracellular compartment than is added in the second half of treatment, a futile and unnecessary event. We propose that changes in dialysis prescription be studied in an attempt to moderate the initial rate of increase in blood [HCO3-] and the magnitude of the body buffer response. These new approaches include either a much lower bath [HCO3-] coupled with an increase in the bath acetate concentration or a stepwise increase in the bath [HCO3-] during treatment. In a subset of patients with low endogenous acid production, we propose reducing the bath [HCO3-] as the sole intervention.

Nephrobronchial fistula is an extremely rare complications of renal infections. We present a case of nephrobronchial fistula in a middle age immunocompetent woman who complained cough and weight loss, with underlying asymptomatic nephrolithiasis. She underwent a chest X-ray that showed left lower lobe infiltrate and abdominal ultrasound. Abdominal ultrasound showed a complicated pyonephrosis ; CT of chest-abdomen-pelvis with intravenous contrast was performed in order to stage and define the extension of the pathology. At CT, a suspected diagnosis of stage III xanthogranulomatous pyelonephritis complicated with pyonephrosis and a nephrobronchial fistula was formulated. A nephrostomy tube was placed, and the patient was treated with antibiotics. Follow up CT, performed after 15 days, showed the healing of the fistulous connection between the perinephric abscess and bronchi; the patient underwent nephrectomy with no airway complication during intubation. Histopathological diagnosis confirmed the presence on complicated xanthogranulomatous pyelonephritis.

Aortoenteric fistula is a life-threatening emergency and is associated with high morbidity and mortality. Prompt surgical intervention before the aneurysm ruptures lowers the mortality rate to about 50%. Potential imaging mimics for aortoenteric fistula include retroperitoneal fibrosis, mycotic aortic aneurysm, and infectious aortitis. Secondary aortoenteric fistula has relative higher incidence compared to primary and is more common with open aortic repair versus endovascular stent graft repair. Ectopic gas in the aneurysm sac and extravasation of enteric contrast into the aneurysm sac is diagnostic for aortoenteric fistula. However, enteric contrast is not recommended for routine evaluation of aortoenteric because the aforementioned finding is extremely rare. More common imaging findings include bowel loop appearing adherent to aneurysm sac with associated inflammatory stranding and foci or ectopic gas within the aneurysm sac or interposed between the bowel and aneurysm sac. Here we present a case of 52-year-old male who presents with incidental primary aortoenteric fistula.

Pleural empyema of extra pulmonary origin is uncommon and empyema secondary to a fistula between the urinary tract and thorax is extremely rare. We report a case of nephropleural fistula causing massive pleural empyema in a 64-year-old woman with a long history of urological problems, including nephrolitiasis and urinary tract infection. She was admitted with sepsis, fever, chills, tachypnea, productive cough and pyuria. At clinical examination, breath sounds were reduced over the left hemithorax. CT revealed a fistulous connection from the upper left calyceal group and the pleural space. Drainage of thoracic and perinephric collection was carried out, but nephrectomy and pleural decortication were required due to haemopurulent urine and decreased hemoglobin levels during the hospitalization. This case demonstrates the unusual and prolonged evolution of an obstructive hydroureteronephrosis complicated by pyonephrosis, culminating in retroperitoneal abscess that fistulized into the pleural space, leading to empyema.

Iatrogenic superior vena cava syndrome (SVCs) represents an emergent diagnostic entity and its correlation with deep vein thrombosis is extremely rare. Recently, the increased use of indwelling lines, pacemakers and intracardiac devices has led to more cases of SVC syndrome also associated with a higher frequency of DVT. We report an unusual complication in a 74-year-old female, who has been undergoing hemodialysis via CVC for 14 years, who referred at our Emergency Department complaining of shortness of breath, headache, face and neck swelling. She underwent chest Computed Tomography Angiography (CTA), that showed a thrombus extending from the superior vena cava to the azygos and hemiazygos veins. Acute SVCs should be suspected in emergency settings in symptomatic patients with indwelling central lines, catheters and pacemakers. CTA represents an accurate and quick imaging modality for the diagnosis and the assessment of the extension of the thrombus.

Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by expansion of a polyglutamine (polyQ)-encoding CAG repeat in the ATXN3 gene. Because the ATXN3 protein regulates photoreceptor ciliogenesis and phagocytosis, we aimed to explore whether expanded polyQ ATXN3 impacts retinal function and integrity in SCA3 patients and transgenic mice.We evaluated the retinal structure and function in five patients with SCA3 and in a transgenic mouse model of this disease (YACMJD84.2, Q84) using optical coherence tomography (OCT) and electroretinogram (ERG). In the transgenic mice, we further: a) determined the retinal expression pattern of ATXN3 and the distribution of cones and rods using immunofluorescence (IF); and b) assessed the retinal ultrastructure using transmission electron microscopy (TEM).Some patients with SCA3 in our cohort revealed: i) reduced central macular thickness indirectly correlated with disease duration; ii) decreased thickness of the macula and the ganglion cell layer, and reduced macula volume inversely correlated with disease severity (SARA score); and iii) electrophysiological dysfunction of cones, rods, and inner retinal cells. Transgenic mice replicated the human OCT and ERG findings with aged homozygous Q84/Q84 mice showing a stronger phenotype accompanied by further thinning of the outer nuclear layer and photoreceptor layer and highly reduced cone and rod activities, thus supporting severe retinal dysfunction in these mice. In addition, Q84 mice showed progressive accumulation of ATXN3-positive aggregates throughout several retinal layers and depletion of cones alongside the disease course. TEM analysis of aged Q84/Q84 mouse retinas supported the ATXN3 aggregation findings by revealing the presence of high number of negative electron dense puncta in ganglion cells, inner plexiform and inner nuclear layers, and showed further thinning of the outer plexiform layer, thickening of the retinal pigment epithelium and elongation of apical microvilli.Our results indicate that retinal alterations detected by non-invasive eye examination using OCT and ERG could represent a biological marker of disease progression and severity in patients with SCA3.

Summary: Background: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p

A Spigelian hernia is a rare hernia, making up approximately 0.1% of all abdominal wall hernias. This hernia goes through a defect in the Spigelian fascia which is the part of the transversus abdominis aponeurosis lateral to the rectus muscle, often at the level of the arcuate line, where the fascia is widest and weakest. Clinical diagnosis is difficult in patients without obvious abdominal mass but imaging can be a valuable adjunct in diagnosis.We report the case of a 64-year-old male who presented to our hospital with small bowel obstruction secondary to an incarcerated Spigelian hernia who was pre-operatively diagnosed with ultrasound and computed tomography. At ultrasound and computed tomography a closed loop obstruction in a Spigelian Hernia was detected, resembling on both imaging modalities a “bulb-like“ appearance.

Background: The Italian Lombardy region has been the epicenter of COVID-19 since February 2020. This study analyses the epidemiology of pediatric type 1 diabetes (T1D) onset during the first two pandemic waves and three previous years. Methods: All the 13 pediatric diabetes centers in Lombardy prospectively evaluated charts of children at T1D onset (0–17 years), during year 2020. After calculating the annual incidence, the data were compared with those of the 3 previous years, using generalized linear models, adjusted for age and sex. Monthly T1D new onsets and diabetic ketoacidosis (DKA) were investigated yearly from 2017 to 2020. Data were extracted from outpatients charts of the pediatric diabetes centers and from the database of the national institute of statistics. Findings: The estimated incidence proportion of T1D was 16/100·000 in 2020, compared to 14, 11 and 12 in 2019, 2018 and 2017, respectively. When adjusting for age and gender, the incidence was significantly lower in 2018 and 2017 compared to 2020 (adjusted incidence ratio: 0.73 and 0.77 respectively, with 95% CI: 0.63 to 0.84, and 0.67 to 0.83; p = 0·002 and p = 0·01), but no difference was found between the years 2020 and 2019. A reduction trend in the percentage of T1D diagnosis during the first wave (March-April) over the total year diagnoses was observed compared to previous years (11·7% in 2020, 17·7% in 2019, 14·1% in 2018 and 14·4% 2017). No difference was observed during the second wave (October-December) (32·8% in 2020, 33·8% in 2019, 34% in 2018, 30·7% in 2017). The proportion of DKA over the total T1D diagnoses during the second wave had higher trend than the first one (41·7% vs 33·3%), while severe DKA over the total DKA appeared higher during the first wave (60% vs 37·1%). Interpretation: The study suggests an increase in the incidence of pediatric T1D in Lombardy throughout the past five years. Pandemic waves may have affected the clinical presentation at onset. Funding: None.

Hypertrophic pyloric stenosis (HPS) is the most important cause of non-bilious vomiting during infancy and it is usually idiopathic. It is very rare in older children and adolescents, in which gastric outlet obstruction (GOO) is more typically secondary to other conditions. Gastrointestinal malformation are frequently associated with Down syndrome and some of them (especially duodenal abnormalities) can be detected quite late. In infants the standard treatment of HPS is represented by a Ramstedt pyloromyotomy, while in adults a distal gastric resection is more indicated and it is usually associated to a Billroth I or II reconstruction. Case report: We present an unusual case of a 12-year-old girl with Down syndrome, diagnosed with late-onset HPS. She came to our attention with periodic non-bilious vomiting and growth delay. She underwent multiple imaging examinations, which highlighted the presence of an HPS. Based on patient's age and the thickness of the pyloric muscle, we decided to perform a partial gastrectomy with a Roux-en-y reconstruction. Patient was discharged on the X day. She is now on follow up, gains weight and presents good conditions. Discussion: HPS is rare but possible during childhood and adolescence. Diagnosis is usually performed through ultrasounds (US) and upper gastrointestinal radiological series (UGI), but sometimes further examinations are required (abdominal MRI, esophagogastroduodenoscopy). In older children since less invasive techniques are not effective, we have to consider partial gastrectomy. Based on our experience, Roux-en-y reconstruction is a valid option, associated with poor complication and good quality of life.

Background: Brucellosis is the most common global bacterial zoonotic disease. Italian annual 2015 report on animal brucellosis control that was submitted to the Integrated National Plan of the Italian Health Ministry showed that the Italian region with the highest prevalence and incidence of brucellosis was Sicily (3.3%). This study aims to demonstrate the burden of disease and the epidemiological trend of human and animal brucellosis in Messina, Sicily, from 1997 to 2016. Methods: The analysis was conducted in the twenty-years 1997–2016. We examined the computerised and paper registers of the Messina Provincial Health Agency n.5 to evaluate human and animal brucellosis reports. Results: 1462 cases of human brucellosis were reported with an important outbreak in 2016 in which were reported 137 cases while the prevalence of infected cattle and sheep/goats decreased from 3.8% and 8%, respectively, in 1997 to 1.7% for both in 2016. A statistically significant correlation was observed between the decrease of both animal and human cases during the considered period. Conclusions: Our study demonstrate that brucellosis is still present in Sicily with a number of cases identified in both animals and humans and it hypothesises a large number of probable underreported cases. Our findings confirm the need to improve knowledge of the risks associated with consuming raw milk and its derivatives, mainly from sheep and goats, and demonstrates that public health would benefit from cooperation between human and veterinary health services. Keywords: Brucellosis, Zoonosis, Epidemiology, Public Health

We present a very rare case of gastric duplication treated with complete excision with two surgical procedures. We decided to report our case to share our experience that confirm the difficult of preoperative/intraoperative diagnosis of gastric duplication in a pediatric patient. Finally we reviewed the literature to date.

The outbreak of COVID-19 raised numerous questions on the interactions between the occurrence of new infections, the environment, climate and health. The European Union requested the H2020 HERA project which aims at setting priorities in research on environment, climate and health, to identify relevant research needs regarding Covid-19. The emergence and spread of SARS-CoV-2 appears to be related to urbanization, habitat destruction, live animal trade, intensive livestock farming and global travel. The contribution of climate and air pollution requires additional studies. Importantly, the severity of COVID-19 depends on the interactions between the viral infection, ageing and chronic diseases such as metabolic, respiratory and cardiovascular diseases and obesity which are themselves influenced by environmental stressors. The mechanisms of these interactions deserve additional scrutiny. Both the pandemic and the social response to the disease have elicited an array of behavioural and societal changes that may remain long after the pandemic and that may have long term health effects including on mental health. Recovery plans are currently being discussed or implemented and the environmental and health impacts of those plans are not clearly foreseen. Clearly, COVID-19 will have a long-lasting impact on the environmental health field and will open new research perspectives and policy needs.

Aims: Bipolar disorders (BDs) and eating disorders (EDs) are both common and severe mental illness and present wide areas of symptomatological overlap. The present study aims to focus on the most significant aspects of this comorbidity. Methods: This review summarizes epidemiology, aethiopathology, prognostic impact, assessment, treatment of comorbidity between BDs and EDs, and comorbidity between bipolar or eating disorders and other psychiatric disorders. We have reviewed articles published in PubMed/Medline, Scopus, Embase, ScienceDirect from 2005 to 2020 concerning comorbidity between eating and bipolar disorders, and systematic reviews or metanalysis on comorbidities between EDs or BDs and other psychiatric disorders. Results: Studies that specifically evaluate the prevalence of EDs in patients with bipolar disorder are more than the studies that investigate the opposite. In BDs, binge eating disorder (BED) represents the most common eating disorder with a prevalence ranging from 8,8% to 28,8%, whereas BN has a prevalence ranging from 4,8% to 10%, and AN from 1% to 7,4%. Instead, in ED patients, prevalence of bipolar disorders ranges from 11,5% to 68.1%.The relationship between EDs and BDs has not been yet investigated enough and consequently has not been totally understood. The presence of EDs has been considered as a marker of clinical severity in patients with bipolar disorders, whereas the presence of bipolar disorder in patients with EDs seems not to have a considerable effect on the age at onset of ED symptoms and on their severity. Comorbidities between EDs or BDs and other psychiatric disorders were also examined. Discussion: Given the strong co-occurrence of eating and bipolar disorder, the treatment for one of these should consider that the other one may co-exist, and therefore should focus on both of them. In patients suffering from one of these disorders, the early screening for the other one should be made. As for pharmacological treatment, it is mandatory to consider that pharmacological treatment effective for one of the two disorders could worsen symptoms of the other, for instance many psychotropic medications could cause weight gain. Further studies are needed to reach an early diagnosis through the development of screening tools, and to deepen aspects of this comorbidity that remain still unknown with particular regard to pharmacological treatment and to biopsychological aspects that might be useful in determining the aetiopathology.

Tumor-related epilepsy is a frequent complication of glioblastoma with seizures often representing the first manifestation of the malignancy. Though tumor resection is associated with improved seizure control, extensive surgery is not always feasible if eloquent cortex is involved in seizure generation and early propagation. We describe a case of a patient with glioblastoma with drug-resistant focal status epilepticus where fluorodeoxyglucose positron emission tomography imaging was successfully used to localize the seizure-onset and optimize tumor resection. This led to successful resection of hypermetabolic tumor tissue and resolution of focal status epilepticus without damage to eloquent cortex.

The global diffusion of benign prostatic hyperplasia (BPH) demands the search for safe and effective treatment alternatives to the drugs commonly used, which exert both side and adverse effects. Among plant-based products, the extracts of Epilobium angustifolium L. (EAEs) could improve BPH symptoms thanks to the presence of ellagitannins and their anti-inflammatory metabolites, urolithins. This study focused its attention on a commercial EAE, standardized to contain ≥ 15 % oenothein B, to determine a) the metabolic profile and the chemical degradation induced by digestion, b) in vivo bioavailability after acute and prolonged treatments of CD1 mice, and c) in vitro antioxidant activity. Utilizing RP-HPLC-PDA-ESI-MSn analysis, 20 different compounds were identified. Polyphenols suffered from degradation after both orogastric and duodenal digestion processes, suggesting that gastro-resistant coating agents are required to preserve the bioactive components occurring in the EAE phytocomplex from orogastric digestion. In vivo data underlined the presence of urolithins only after the prolonged treatment, confirming that the gut fermentation process requires at least 24 h to produce urolithins. Finally, an increase of Superoxide Dismutase-1 (SOD-1), which represents one of the fundamental endogenous antioxidant defenses, was determined in an EAE pretreated LNCap cell model system, confirming EAE antioxidant activity.

The World Health Organization Global Action Plan recommends integrated surveillance programs as crucial strategies for monitoring antibiotic resistance. Although several national surveillance programs are in place for clinical and veterinary settings, no such schemes exist for monitoring antibiotic-resistant bacteria in the environment. In this transnational study, we developed, validated, and tested a low-cost surveillance and easy to implement approach to evaluate antibiotic resistance in wastewater treatment plants (WWTPs) by targeting cefotaxime-resistant (CTX-R) coliforms as indicators. The rationale for this approach was: i) coliform quantification methods are internationally accepted as indicators of fecal contamination in recreational waters and are therefore routinely applied in analytical labs; ii) CTX-R coliforms are clinically relevant, associated with extended-spectrum β-lactamases (ESBLs), and are rare in pristine environments. We analyzed 57 WWTPs in 22 countries across Europe, Asia, Africa, Australia, and North America. CTX-R coliforms were ubiquitous in raw sewage and their relative abundance varied significantly (

Mesenchymal stem cells (MSC) are heterogeneous cells of complex nature that show different potentials while different culture conditions can modify their functionalities through interactions with the microenviroment. Here, we found that bone marrow (BM) MSC from different donor sources and passages that expressed higher levels of α6 integrin subunit (ITGA6), showed higher clonogenicity, migration and differentiation potential. ITGA6 showed important roles improving these potentials and regulating proliferation through protein kinase B (AKT) pathway and cell cycle inhibitor proteins p53 and p21. Moreover, ITGA6 downregulation impaired migration. Cell confluence regulated ITGA6, increasing its expression in low density cultures and decreasing in high density cultures. Besides, ITGA6- cells expressed ITGA6 when seeded at low densities. We found higher ITGA6 expression on fibronectin substrates at lower confluency. Fibronectin increased proliferation, clonogenicity, activation of AKT, decreased cell cycle inhibitor proteins and augmented growth factors expression. Spheres-derived MSC showed higher ITGA6 expression and enhanced potentials for migration, clonogenicity and proliferation. In conclusion, though there is an intrinsic regulation of ITGA6 expression, associated to the progenitor potential of BM-MSC, this expression is regulated by culture conditions and is translated in changes in cell behavior and proliferation. This knowledge could be used to enhance the potential of BM-MSC for clinical application.

Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions and is found in high concentrations in the serotonergic cell bodies of origin of these projections (raphe nuclei).Twenty-eight participants with mild cognitive impairment (age 66.6 ± 6.9, 16 males) and 28 healthy, cognitively normal, demographically matched controls (age 66.2 ± 7.1, 15 males) underwent magnetic resonance imaging for measurement of grey matter volumes and high-resolution positron emission tomography with well-established radiotracers for the serotonin transporter and regional cerebral blood flow. Beta-amyloid imaging was performed to evaluate, in combination with the neuropsychological testing, the likelihood of subsequent cognitive decline in the participants with mild cognitive impairment. The following hypotheses were tested: 1) the serotonin transporter would be lower in mild cognitive impairment compared to controls in cortical and limbic regions, 2) in mild cognitive impairment relative to controls, the serotonin transporter would be lower to a greater extent and observed in a more widespread pattern than lower grey matter volumes or lower regional cerebral blood flow and 3) lower cortical and limbic serotonin transporters would be correlated with greater deficits in auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls.Reduced serotonin transporter availability was observed in mild cognitive impairment compared to controls in cortical and limbic areas typically affected by Alzheimer's disease pathology, as well as in sensory and motor areas, striatum and thalamus that are relatively spared in Alzheimer's disease. The reduction of the serotonin transporter in mild cognitive impairment was greater than grey matter atrophy or reductions in regional cerebral blood flow compared to controls. Lower cortical serotonin transporters were associated with worse performance on tests of auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls.The serotonin system may represent an important target for prevention and treatment of MCI, particularly the post-synaptic receptors (5-HT4 and 5-HT6), which may not be as severely affected as presynaptic aspects of the serotonin system, as indicated by the observation of lower serotonin transporters in MCI relative to healthy controls.

This Data in Brief contains results from three different survey logistic regression models comparing risks of self-reported diagnoses of cardiovascular and pulmonary diseases among smokers of menthol and non-menthol cigarettes. Analyses employ data from National Health and Nutrition Examination Survey (NHANES) cycles administered between 1999 and 2012, combined and in subsets. Raw data may be downloaded from the National Center for Health Statistics. Results were not much affected by which covariates were included in the models, but depended strongly on the NHANES cycles included in the analysis. All three models returned elevated risk estimates for three endpoints when they were run in individual NHANES cycles (congestive heart failure in 2001–02; hypertension in 2003–04; and chronic obstructive pulmonary disease in 2005–06), and all three models returned null results for these endpoints when data from 1999–2012 were combined.

Chondroblastoma is a rare and benign bone tumor that can occur in the craniofacial region. It may be difficult to diagnose using imaging alone; histological analyses and even immunohistochemical analyses are often required. This article reports on a rare case of chondroblastoma of the temporomandibular joint. Its diagnosis was hindered by its similarity to other tumors in both imaging exams and histological analyses. It was definitively treated through the total excision of the tumor. Keywords: Chondroblastoma, Temporomandibular joint, Immunohistochemical analyses

Patent ductus arteriosus (PDA) in preterm babies is common and related to high morbidity and mortality if left untreated. Although its optimal management is still debated, surgical ligation or clipping remain the only available options for pharmacologically unresponsive PDAs. The surgical procedure adds its own risk to this fragile population. We report the first case of premature neonate with a left upper pulmonary lobe venous infarction, following PDA ligation.

Oxidative stress, hepatic steatosis, and mitochondrial dysfunction are key pathophysiological features of nonalcoholic fatty liver disease. A conjugated linoleic acid (CLA) mixture of cis9,trans11 (9,11-CLA) and trans10,cis12 (10,12-CLA) isomers enhanced the antioxidant/detoxifying mechanism via the activation of nuclear factor E2-related factor-2 (Nrf2) and improved mitochondrial function, but less is known about the actions of specific isomers. The differential ability of individual CLA isomers to modulate these pathways was explored in Wistar rats fed for 4 weeks with a lard-based high-fat diet (L) or with control diet (CD), and, within each dietary treatment, two subgroups were daily administered with 9,11-CLA or 10,12-CLA (30 mg/day). The 9,11-CLA, but not 10,12-CLA, supplementation to CD rats improves the GSH/GSSG ratio in the liver, mitochondrial functions, and Nrf2 activity. Histological examination reveals a reduction of steatosis in L-fed rats supplemented with both CLA isomers, but 9,11-CLA downregulated plasma concentrations of proinflammatory markers, mitochondrial dysfunction, and oxidative stress markers in liver more efficiently than in 10,12-CLA treatment. The present study demonstrates the higher protective effect of 9,11-CLA against diet-induced pro-oxidant and proinflammatory signs and suggests that these effects are determined, at least in part, by its ability to activate the Nrf2 pathway and to improve the mitochondrial functioning and biogenesis.

Mutations in MLC1 cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), a disorder characterized clinically by macrocephaly, deterioration of motor functions, epilepsy and mental decline. Recent studies have detected MLC1 mRNA and protein in astroglial processes. In addition, our group previously reported MLC1 expression in some neurons in the adult mouse brain. Here we performed an exhaustive study of the expression pattern of MLC1 in the developing mouse brain by means of optic and electron microscopy. In the central nervous system, MLC1 was detected mainly in axonal tracts early in development. In addition, MLC1 was also observed in the peripheral nervous system and in several sensory epithelia, as retina or saccula maculae. Post-embedding immunogold experiments indicated that MLC1 is localized in astrocyte–astrocyte junctions, but not in the perivascular membrane, indicating that MLC1 is not a component of the dystrophin–glycoprotein complex. In neurons, MLC1 is located at the plasma membrane and vesicular structures. Our data provide a mouse MLC1 expression map that could be useful to understand the phenotype of MLC patients, and suggested that MLC disease is caused by an astrocytic and a neuronal dysfunction.

The very low density lipoprotein (VLDL) receptor is a member of the low density lipoprotein supergene family of receptors in which differential splicing of mRNA has been reported. We present several lines of evidence showing that bovine aortic endothelial cells exclusively express a VLDL receptor isoform that lacks the O-linked sugar domain i) Western and receptor-associated protein (RAP) ligand blotting gave a single band of about 99 kDa in membrane extracts of bovine aortic endothelial cells (BAEC). ii) Screening of the BAEC cDNA library with the previously characterized human VLDL receptor cDNA as a probe gave several C-terminal-positive clones; all lacked the 84 nucleotides corresponding to exon 16. Polymerase chain reaction (PCR) confirmed that VLDL receptor cDNA encoding exon 16 was absent from the library. iii) Reverse transcription (RT)-PCR analysis of the BAEC mRNA using a pair of oligonucleotide primers that flank the deletion gave only one band of 136 nt. iv) Semiquantitative RT-PCR analysis showed that only the non-O-glycosylated variant was expressed in BAEC. Cell-binding studies with antibodies against the N-terminal domain showed that the BAEC VLDL receptor is present at the plasma membrane, suggesting that the non-glycosylated variant could be functional. In addition, RT-PCR performed in bovine tissues showed that the variant containing the O-linked sugar domain is preferentially expressed in heart, brain, and skeletal muscle, whereas the non-O-glycosylated spliced variant is found in all tissues analyzed. Taken together these results suggest that the differential splicing of the VLDL receptor is cell- and tissue-specific and that the functions of the receptor could depend on the cell type. —Magrané, J., M. Reina, R. Pagan, A. Luna, R. P. Casaroli-Marano, B. Angelin, M. Gåfvels, and S. Vilaró. Bovine aortic endothelial cells express a variant of the very low density lipoprotein receptor that lacks the O-linked sugar domain. J. Lipid Res. 1998. 39: 2172–2181.

The cellular mechanisms and pathways by which lipoprotein lipase (LPL) enhances the binding and uptake of lipoproteins remains unknown. Confocal and immunoelectron microscopy demonstrated that primary binding of bovine LPL (bLPL) occurs at the microvilli surface of HepG2 cells and hepatocytes. Internalized bLPL was associated with endocytic vesicles and multivesicular bodies. Quantitative immunofluorescence indicated that the presence of bLPL caused a marked increase in the cell-surface binding of DiI-conjugated triacylglycerol-rich lipoproteins (DiI-TRL). Confocal microscopy showed that when DiI-TRL was incubated with bLPL at 4°C, the distributions of bound LPL and DiI-TRL were totally coincident, and covered the apical surface of both HepG2 cells and hepatocytes. When incubated separately, the time-courses of the internalization of fluorescence associated with DiI-TRL and bLPL were different: DiI-TRL was quickly internalized by both HepG2 cells and hepatocytes, and reached a plateau at 30 min, whereas intracellular LPL increased continuously, but more slowly in the same period. In the presence of bLPL, DiI-TRL was internalized progressively by HepG2 and by cultured hepatocytes for up to 1 h and no saturation was reached. At this time the intensity of labeling of bLPL was lower than of DiI-TRL and a higher number of DiI spots did not colocalize with bLPL immunofluorescence, suggesting that the ligands follow a different pathway after internalization. The data suggest that when lipoprotein lipase (LPL) is associated with the lipoproteins it directs them to specific endocytic pathways. A hypothetical model of the intracellular pathways followed by triacylglycerol-rich lipoproteins and LPL after internalization is proposed.—Casaroli-Marano, R. P., R. García, E. Vilella, G. Olivecrona, M. Reina, and S. Vilaró. Binding and intracellular trafficking of lipoprotein lipase and triacylglycerol-rich lipoproteins by liver cells. J. Lipid Res. 1998. 39: 789–806.

Ocular tissues are highly dependent on lipid turnover and metabolism, which requires an uptake mechanism for fatty acids from lipoproteins. We studied the activity and expression of lipoprotein lipase (LPL), which catalyzes the hydrolysis of plasma triglycerides, in different ocular regions. Human and bovine eyes were dissected and various specialized anatomical areas were assayed for LPL activity, mRNA, and immunoreactivity. Variable levels of LPL activity were detected in all structures in human and bovine eyes. LPL activity was much higher in vascularized structures, such as ciliary body, iris, and retina than in avascular eye structures, such as vitreous body, lens, and cornea. In both human and bovine eyes, ciliary body contained the highest LPL lipolytic activity. LPL mRNA was detected by reverse transcription followed by polymerase chain reaction (RT-PCR) in all regions of human eyes. By RT-PCR analysis it was shown that bovine eyes contained high levels of LPL mRNA in ciliary body and iris, lower levels were found in retina, optic nerve, and lens, whereas no LPL mRNA could be found in bovine cornea. RT-PCR data, obtained in bovine eyes, agree with the results obtained by Northern blot experiments, confirming the high levels of LPL mRNA in iris and ciliary body. Immunofluorescence experiments performed on human eye samples indicated that the LPL protein is mostly distributed on the choroides, the choriocapillaris, and on the vessels of ciliary body, iris, optic nerve, and retina. The present study demonstrates that active LPL protein is synthesized, secreted, and located among microvessels in several specialized regions of the eye, and suggests that LPL could be involved in the uptake of fatty acids by the ocular tissues.