Impaired saccadic eye movement in diabetic patients: the relationship with visual pathways function

The aim of this study was to evaluate whether a correlation existed between saccadic eye movements and visual pathways function in diabetic patients. Saccadic or fast Eye Movement System (EMS) and Visual Evoked Potentials (VEPs) were assessed in 20 insulin-dependent diabetic mellitus (IDDM) patients without long-term complications and in stable metabolic control and in 21 age-matched control subjects. In IDDM patients we observed significantly (p<0.01) longer EMS latency, while EMS velocity and accuracy were similar to those of controls; VEPs showed a significant delay in N75, P100, N145 latencies and significant reduction of N75-P100 and P100-N145 amplitudes. In IDDM patients no relationships between EMS and VEP parameters were found. In conclusion, EMS latency delay suggests an impairment of the saccadic eye movement system, while impaired VEPs may be ascribed to a dysfunction of the visual pathways. The lack of correlation between VEPs impairment and EMS latency delay suggests that in our IDDM patients the delay of saccadic latency cannot be exclusively related to a visual pathways dysfuction and could be ascribed to a diffuse neuronal involvement. This revised version was published online in July 2006 with corrections to the Cover Date.     

Visual stimulation and frequency of focal neurological symptoms engage distinctive neurocognitive resources in migraine with aura patients: a study of resting-state functional networks

IntroductionSeveral functional neuroimaging studies on healthy controls and patients with migraine with aura have shown that the activation of functional networks during visual stimulation is not restricted to the striate system, but also includes several extrastriate networks.MethodsBefore and after 4 min of visual stimulation with a checkerboard pattern, we collected functional MRI in 21 migraine with aura (MwA) patients and 18 healthy subjects (HS). For each recording session, we identified independent resting-state networks in each group and correlated network connection strength changes with clinical disease features.ResultsBefore visual stimulation, we found reduced connectivity between the default mode network and the left dorsal attention system (DAS) in MwA patients compared to HS. In HS, visual stimulation increases functional connectivity between the independent components of the bilateral DAS and the executive control network (ECN). In MwA, visual stimulation significantly improved functional connectivity between the independent component pairs salience network and DAS, and between DAS and ECN. The ECN Z-scores after visual stimulation were negatively related to the monthly frequency of aura.ConclusionsIn individuals with MwA, 4 min of visual stimulation had stronger cognitive impact than in healthy people. A higher frequency of aura may lead to a diminished ability to obtain cognitive resources to cope with transitory but important events like aura-related focal neurological symptoms.     

Effect ofd-fenfluramine on the indole contents of the rat brain after treatment with different inducers of cytochrome P450 isoenzymes

The effects of pretreatment with inducers of hepatic cytochrome P450 isoenzymes (phenobarbital, dexamethasone and-naphthoflavone) on the metabolism ofd-fenfluramine (d-F) and its acute and long-lasting indole-depleting effects were studied in rats, in an effort to obtain further information on the importance of hepatic drug metabolism in relation to its neurochemical actions. Twenty-four hours after the last dose of each inducer, rats were injected withd-F hydrochloride (5 mg/kg, IP) and killed at various times thereafter for parallel determination of indoles and drug concentrations in plasma and brain. Additional rats were treated as above and killed 1 week afterd-F hydrochloride (5 and 10 mg/kg) to study the recovery of indole in the cortex, a particularly sensitive brain area. Phenobarbital and-naphthoflavone and, to a lesser degree, dexamethasone, stimulated the metabolism ofd-F, as evidenced by a decrease in plasma and brain areas under the curve (AUC) compared to vehicle-treated rats. This indicated that multiple isoenzymes are capable of mediating the drug's metabolism, primarily byN-dealkylation tod-norfenfluramine (d-NF). None of the inducers raised plasma and brain AUC of the nor-derivative, and in fact phenobarbital and particularly-naphthoflavone reduced it. These different effects were even apparent in rats givend-NF (2.5 mg/kg), indicating that both phenobarbital and-naphthoflavone also stimulate the sequential metabolism of the nor-metabolite (byN-deamintaion) which, however, is apparently enhanced most actively by-naphthoflavone-inducible forms of P-450. Total active brain concentrations (d-F+d-NF) after the different pretreatments were in the order of-naphthoflavone < phenobarbital < dexamethasone vehicle. Interestingly,-naphthoflavone rapidly reversed the depletion of brain indoles caused byd-F (andd-NF); phenobarbital provided partial protection and dexamethasone did not appreciably modify either the acute or long-term neurochemical effects of the drug. The fact that phenobarbital affectedd-NF kinetics less than-naphthoflavone, and provided only partial protection against the acute and long-lasting neurochemical effects of high doses ofd-F, further stresses the critical role ofd-NF in the neurochemical outcome of its parent drug. These findings support the view that the degree and duration of the indole-depleting effects are related to critical brain concentrations of the parent compound and its nor-derivative, and provide indirect evidence that hepatic metabolites other thand-NF are unlikely to play any role in the neurochemical effects of high doses ofd-F in rats.     

Liquid Biopsy at Home: Delivering Precision Medicine for Patients with Cancer During the COVID-19 Pandemic

CoronaVirus disease-2019 has changed the delivery of health care worldwide and the pandemic has challenged oncologists to reorganize cancer care. Recently, progress has been made in the field of precision medicine to provide to patients with cancer the best therapeutic choice for their individual needs. In this context, the Foundation Medicine (FMI)-Liquid@Home project has emerged as a key weapon to deal with the new pandemic situation. FoundationOne Liquid Assay (F1L) is a next-generation sequences-based liquid biopsy service, able to detect 324 molecular alterations and genomic signatures, from May 2020 available at patients’ home (FMI-Liquid@Home). We analyzed time and costs saving for patients with cancer, their caregivers and National Healthcare System (NHS) with FMI-Liquid@Home versus F1L performed at our Department. Different variables have been evaluated. Between May 2020 and August 2021, 218 FMI-Liquid@Home were performed for patients with cancer in Italy. Among these, our Department performed 153 FMI-Liquid@Home with the success rate of 98% (vs. 95% for F1L in the hospital). Time saving for patients and their caregivers was 494.86 and 427.36 hours, respectively, and costs saving was 13 548.70€. Moreover, for working people these savings were 1084.71 hours and 31 239.65€, respectively. In addition, the total gain for the hospital was 163.5 hours and 6785€, whereas for NHS was 1084.71 hours and 51 573.60€, respectively. FMI-Liquid@Home service appears to be useful and convenient allowing time and costs saving for patients, caregivers, and NHS. Born during the COVID-19 pandemic, it could be integrated in oncological daily routine in the future. Therefore, additional studies are needed to better understand the overall gain and how to integrate this service in different countries.     

Pharmacological closure of patent ductus arteriosus: effects on pulse pressure and on endothelin-1 and vasopressin excretion

Widened pulse pressure is a classic sign of significant left-to-right shunting patent ductus arteriosus (PDA), but little evidence supports this statement in the early life of premature infants with respiratory distress syndrome (RDS) needing nonsteroidal anti-inflammatory drugs (NSAIDs), the pharmacological treatment for PDA. Pulse pressure and urinary endothelin-1 (ET-1) and arginine vasopressin (AVP) vasoactive factors involved in the transitional circulation were measured before and after the NSAIDs treatment of 46 RDS premature infants receiving either ibuprofen (n = 22) or indomethacin (n = 24), with 28 responders and 18 nonresponders to the first NSAIDs course. We found that following pharmacological PDA closure, systolic and diastolic blood pressure significantly increased, maintaining a stable pulse pressure. However, when pharmacological closure failed, the trend (nonsignificant) was for a more consistent increase in systolic than in diastolic blood pressure, which determined a statistically significant widening pulse pressure. In addition, urinary ET-1 excretion rates decreased significantly after PDA closure, whereas persistent more aggressive pharmacological therapy failed. Urinary AVP excretion rates decreased insignificantly after therapy, uninfluenced by the efficacy of the drugs. We concluded that widened pulse pressure is a clinical sign of failed PDA pharmacological closure in RDS premature infants. ET-1 levels remain elevated when NSAIDs fail to interrupt left-to-right PDA shunting that complicates recovery from RDS.     

Simultaneous ovarian and endometrial osseous metaplasia: a case report

BACKGROUND: Endometrial ossification is a rare disease. More than 80% of cases occur after pregnancy, but it has been observed in patients with a history of endometritis, dilation and curettage, and metabolic disorders. CASE: A 42-year-old woman presented with osseous metaplasia of both the endometrium and ovaries. At laparoscopy both adnexa were covered with adhesions and were adherent to the posterior wall of the uterus. Following adhesiolysis, calcified nodules were removed from both ovaries with biopsy forceps. Endometrial bone tissue was removed by hysteroscopic resection. CONCLUSION: To our knowledge, this is the first reported case of osseous metaplasia of both the endometrium and ovaries since all cases described to date in the literature involved only the uterine cavity. Conservative management with endoscopic surgery is effective.     

Effectiveness of fetal fibronectin testing compared with digital cervical assessment of women with preterm contractions

The purpose of this study is to determine the effectiveness of fetal fibronectin (FFN) compared to assessment of cervical dilation (CD) in clinical management of women with symptomatic preterm labor (PTL). Pregnant women presenting to Thomas Jefferson University Hospital between May 1, 2001 and November 30, 2002 with symptomatic PTL underwent FFN sampling and had a complete clinical evaluation including a pelvic bimanual examination. Inclusion criteria were singleton pregnancy, gestational age (GA) between 24 (0) and 33 (6) weeks, CD < 3 cm, and intact amniotic membranes. FFN samples were sent out and results were available within 4-12 hours. Clinical management including tocolysis, antenatal steroids, and hospitalization was determined based on digital CD assessment and FFN status. A dilated cervix was defined as CD > 1 cm. Ninety-three patients were included. Spontaneous preterm delivery (SPTD) at < 37 weeks occurred in 20 of 93 (21.5%) patients. Medical therapy use was significantly higher in patients with dilated cervix than in those with a closed cervix (all P values < 0.05). Tocolysis and steroid use in FFN-negative patients and FFN-positive patients were not significantly different. Furthermore, tocolytic use was higher in FFN-negative patients than in women with positive FFN (50% versus 42.1%; P = 0.53). Use of antenatal steroids was similar in patients with CD >/= 1 cm and a positive FFN (54.5% versus 47.4%; P = 0.92). Compared with FFN-negative patients, women with closed cervix were less likely to undergo interventions. In symptomatic PTL patients, CD determined clinical management more than FFN status. Overall, the use of FFN was not effective in decreasing "unnecessary" clinical interventions.     

Photoprotective and Antiaging Effects of a Standardized Red Orange (Citrus sinensis (L.) Osbeck) Extract in Asian and Caucasian Subjects: A Randomized,Double-Blind,Controlled Study

The increase in solar ultraviolet radiation (UVR) that reaches the Earth’s surface should make us reflect on the need to develop new approaches in protecting the skin from UVR exposure. The present study aims to evaluate the photoprotective and antiaging efficacy of a red orange extract (100 mg/day) in both Asian and Caucasian subjects. A randomized, double-blind, controlled study was carried out in 110 Asian and Caucasian subjects. Product efficacy was measured as follows: (1) the photoprotective effect was measured by the minimal erythema dose (MED) assessment; (2) the efficacy in decreasing the UVA+B-induced skin redness was measured by colorimetry; (3) the antioxidant efficacy was measured by the ferric-reducing antioxidant power (FRAP) and the malondialdehyde (MDA) assay; and (4) skin moisturization, skin elasticity, skin radiance, the intensity of melanin staining, transepidermal water loss (TEWL), and wrinkles were measured to assess the antiaging efficacy. The intake of the product for 56 days was effective in improving the skin reaction to UV exposure; in increasing the skin antioxidant capacity as well as in decreasing UVA-induced lipid peroxidation; in increasing the skin moisturization, skin elasticity, and skin radiance; and in decreasing TEWL, the intensity of melanin staining inside dark spots, and wrinkle depth. Our results suggest that the test product is effective in counteracting both the harmful effects of UVR exposure and aging signs.