A 19 to 17 Ma amagmatic extension event at the Mid-Atlantic Ridge: Ultramafic mylonites from the Vema Lithospheric Section

A >300 km long lithospheric section (Vema Lithospheric Section or VLS) is exposed south of the Vema transform at 11°N in the Atlantic. It is oriented along a seafloor spreading flow line and represents ∼26 Ma of accretion at a single 80 km long segment (EMAR) of the Mid-Atlantic Ridge. The basal part of the VLS exposes a mantle unit made mostly of relatively undeformed coarse-grained/porphyroclastic peridotites that were sampled at close intervals. Strongly deformed mylonitic peridotites were found at 14 contiguous sites within a ∼80 km stretch (∼4.7 Ma interval); they are dominant in a time interval of 1.4 Ma, from crustal ages of 16.8 to 18.2 Ma (mylonitic stretch). Some of the mylonites are "dry," showing anhydrous high-T deformation, but most contain amphibole. The mylonitic peridotites tend to be less depleted than the porphyroclastic peridotites on the basis of mineral major and trace elements composition, suggesting that the mylonites parent was a subridge mantle that underwent a relatively low degree of melting. The Sr, Nd, and O isotopic composition of the amphiboles is MORB-like and suggests either that seawater did not contribute to their isotopic signature or that their isotopic ratios re-equilibrated during fluid circulation in the upper mantle. Four 40Ar/39Ar ages, on three amphiboles separated from the peridotites, are close to crustal ages predicted from magnetic anomalies, confirming that the amphiboles formed close to ridge axis. We propose that crustal accretion at the EMAR segment has been mostly symmetrical for the 26 Ma of its recorded history, except for the ∼1.4 Ma interval of prevalent ultramafic mylonites (mylonitic stretch) that may record a period of quasi-amagmatic asymmetric accretion of oceanic lithosphere close to the ridge–Vema transform intersection, possibly with development of detachment faults. This interval may correspond to a thermal minimum of the subridge upwelling mantle, marking the transition from a period of decreasing to one of increasing mantle melting below the EMAR segment

Synthesis and NLRP3-Inflammasome Inhibitory Activity of the Naturally Occurring Velutone F and of Its Non-Natural Regioisomeric Chalconoids

Plant-derived remedies rich in chalcone-based compounds have been known for centuries in the treatment of specific diseases, and nowadays, the fascinating chalcone framework is considered a useful and, above all, abundant natural chemotype. Velutone F, a new chalconoid from Millettia velutina, exhibits a potent effect as an NLRP3-inflammasome inhibitor; the search for new natural/non-natural lead compounds as NLRP3 inhibitors is a current topical subject in medicinal chemistry. The details of our work toward the synthesis of velutone F and the unknown non-natural regioisomers are herein reported. We used different synthetic strategies both for the construction of the distinctive benzofuran nucleus (BF) and for the key phenylpropenone system (PhP). Importantly, we have disclosed a facile entry to the velutone F via synthetic routes that can also be useful for preparing non-natural analogs, a prerequisite for extensive SAR studies on the new flavonoid class of NLRP3-inhibitors

Значение пластики лоскутом на временной питающей ножке в замещении раневых дефектов

РАНЫ И ТРАВМЫ /ХИРКОЖИ ТРАНСПЛАНТАЦИЯПЕРЕСАДКА КОЖИДЕРМАТОПЛАСТИКАЛОСКУТЫХИРУРГИЧЕСКИЕ ЛОСКУТЫХИРУРГИЧЕСКИЕ ОПЕРАЦИИ ВОССТАНОВИТЕЛЬНЫЕ /МЕТОДЫИТАЛЬЯНСКАЯ ПЛАСТИКАПЛАСТИКА ИТАЛЬЯНСКАЯРАНЕВЫЕ ПОКРЫТИЯЦель. Провести комплексный анализ возможностей, технических особенностей и недостатков методики пластики ран перемещенным из отдаленных областей сложносоставным кожным лоскутом на временной питающей ножке при закрытии раневых дефектов конечностей. Материал и методы. В исследование включено 14 пациентов с раневыми дефектами конечностей различного происхождения, которым на восстановительном этапе лечения применен метод пластики перемещенным из отдаленных областей сложносоставным кожным лоскутом на временной питающей ножке. Раневые дефекты имели различное происхождение (глубокие отморожения, хронический остеомиелит, нейротрофические нарушения), локализацию и площадь. Показанием к данному виду полнослойной пластики служила необходимость закрытия раны в функционально значимой зоне и невозможность применения других, более простых методов кожной пластики. Результаты. Положительный ближайший результат лечения получен во всех 14 случаях перемещения полнослойных кожных лоскутов из отдаленных частей тела. В 3 случаях в раннем послеоперационном периоде отмечено развитие осложнений (критический перегиб ножки лоскута, подлоскутная гематома, краевой некроз лоскута), не повлиявших существенно на ближайший результат операции. Отдаленные результаты лечения оценены у 8 пациентов в сроки от 1 до 22 лет после операции. Ключевым моментом, определяющим отдаленный результат лечения, стала комплаентность пациента в условиях денервации лоскута и закрытия ран в функционально значимых областях. В двух случаях у пациентов, не соблюдающих рекомендации, произошел некроз лоскута в зоне опорной поверхности стопы. В остальных наблюдениях получен стойкий положительный результат. Заключение. Пластика ран перемещенным из отдаленных областей сложносоставным кожным лоскутом является эффективным методом реконструкции в функционально значимых областях в условиях ограниченных пластических резервов окружающей кожи. Денервация таких лоскутов предъявляет дополнительные требования к пациентам в плане соблюдения рекомендаций. Успех операции в отдаленные сроки во многом определяется комплаентностью пациента.Objective. Comprehensive analysis of opportunities, technical features and disadvantages of wound plasty with distant pedicled flap closing wound defects of the limbs was performed. Methods. The study included 14 patients with limb wounds of different origin, who were treated using distant pedicled flaps grafting. Wounds were of different origin (deep frostbites, chronic osteomyelitis, neurotrophic disorders), diverse localization and perimeter. The indication for this type of full-layer plastics was the need to treat the wound in a functionally significant zone and the impossibility of using other, less complex methods of skin grafting. Results. A positive immediate result of treatment was obtained in all 14 cases of distant flaps grafting. The development of complications (critical bend of the pedicle of the flap, sub-flap hematoma, the flap’s edge necrosis) was registered in 3 cases in the early postoperative period, those complications did not significantly affect the immediate outcome of the operation. Long-term outcomes of treatment were evaluated in 8 patients in terms from 1 to 22 years after the operation. The key point determining the long-term treatment outcome was the patient’s compliance in the conditions of denervation of the flap and closure of wounds in functionally important areas. A flap necrosis in the plantar area occurred in two cases in patients, who did not follow the recommendations. In the remaining observations a stable positive result was obtained. Conclusions. The distant pedicled flaps grafting is an effective method of reconstruction in functionally important areas under the conditions of limited plastic reserves of the surrounding skin. Denervation of such flaps exposes additional requirements to patients in terms of compliance with recommendations. The success of the operation in the long term period is largely determined by the patient’s compliance

Slippages .... exploring the aesthetic encounter from the perspective of Merleau-Ponty's ontology

This paper addresses the aesthetic encounter from the perspective of the writings of Maurice Merleau-Ponty on the visible and the invisible. It begins with the premise that from time to time we encounter situations which precipitate a sense of slippage in our experience of the world. The paper proceeds to argue that the arts can provide a point of access to this experience, and that aesthetic theory has, for example, responded to it through the development of the notion of 'the sublime'. The writings of Maurice Merleau-Ponty and, in particular, aspects of his text The Visible and the invisible, are presented with a view to augmenting this aspect of aesthetic theory. Proceeding from a 'Merleau-Pontian' perspective, the paper explores how the arts can serve to disrupt our conventional sense of space and time - creating ripples in the substance Merleau-Ponty names as 'flesh' - so as to expose the chiasm or blind spot in our experience of the world. The methodology adopted is an experiential one, which draws on the writer's interaction with the selected works of various artists as well as her own practice in glass

Divergent long-term detection rates of proximal and distal advanced neoplasia in fecal immunochemical test screening programs: A retrospective cohort study

Background: Short-term studies have reported that the fecal immunochemical test (FIT) is less accurate in detecting proximal than distal colorectal neoplasia. Objective: To assess the long-term detection rates for advanced adenoma and colorectal cancer (CRC), according to anatomical location. Design: Retrospective study. Setting: Population-based, organized screening program in the Veneto region of Italy. Participants: Persons aged 50 to 69 years who completed 6 rounds of FIT screening. Measurements: At each screening round, the detection rates for advanced adenoma and cancer, as well as the proportional interval cancer rate (PICR), were calculated by anatomical location (proximal colon, distal colon, or rectum). Results: Between 2002 and 2014, a total of 123 347 participants had 441 647 FITs. The numbers of advanced adenomas and cancer cases detected, respectively, were 1704 and 200 in the proximal colon, 3703 and 324 in the distal colon, and 1220 and 209 in the rectum. Although the detection rate for proximal colon cancer declined only from the first to the second screening round (0.63 to 0.36 per 1000 screenees), the rate for both distal colon and rectal cancer steadily decreased across 6 rounds (distal colon, 1.65 in the first round to 0.17 in the sixth; rectum, 0.82 in the first round to 0.17 in the sixth). Similar trends were found for advanced adenoma (proximal colon, 5.32 in the first round to 4.22 in the sixth; distal colon, 15.2 in the first round to 5.02 in the sixth). Overall, 150 cases of interval cancer were diagnosed. The PICR was higher in the proximal colon (25.2% [95% CI, 19.9% to 31.5%]) than the distal colon (6.0% [CI, 3.9% to 8.9%]) or rectum (9.9% [CI, 6.9% to 13.7%]). Limitations: Participants with irregular attendance were censored. Those who had a false-positive result on a previous FIT but negative colonoscopy results were included in subsequent rounds. Conclusion: This FIT-based, multiple-round, long-term screening program had a negligible reduction in detection rates for neoplastic lesions in the proximal versus the distal colon after the first round. This was related to a higher PICR in the proximal colon and suboptimal efficacy in preventing the age-related proximal shifting of CRC. Primary Funding Source: None

Long-term performance of colorectal cancer screening programmes based on the faecal immunochemical test

BACKGROUND: The long-term performance of colorectal cancer (CRC) screening programmes based on a 2-year faecal immunochemical test (FIT) is still unclear. METHODS: In a sample of 50 to 69-year-olds repeatedly screened with the FIT (OC-Hemodia latex agglutination test; cut-off: 20\u2009\ub5g haemoglobin/g faeces), we examined: (1) the FIT positivity rate, the CRC and advanced adenoma detection rate and the FIT's positive predictive value (PPV) for advanced neoplasia, at each round of screening and (2) the cumulative CRC and advanced adenoma detection rate after five rounds of FIT. RESULTS: Over 12 years (2002-2014), 123\u2009347 individuals were administered the FIT up to six times, and 781 CRCs and 4713 advanced adenomas were diagnosed. The CRC and advanced adenoma detection rates declined substantially from the first to the third (rate ratio (RR) 0.25, 95%\u2009CI 0.20 to 0.32) and second (RR 0.51, 95%\u2009CI 0.47 to 0.56) rounds, respectively, and then remained stable. The PPV for advanced neoplasia dropped by 18% in the second round (RR 0.82, 95%\u2009CI 0.77 to 0.89), with no further reduction thereafter due to a concomitant decline in the FIT positivity rate (RR first to sixth rounds: 0.56, 95%\u2009CI 0.53 to 0.60).The cumulative CRC and advanced adenoma detection rates over five consecutive rounds were 8.5\u2030 (95%\u2009CI 7.8 to 9.2), and 58.9\u2030 (95%\u2009CI 56.9 to 61.0), rectively. CONCLUSIONS: Repeated FIT significantly reduces the burden of colorectal disease while facilitating an efficient use of colonoscopy resources. The cumulative detection rate after five rounds of FIT is similar to primary screening with colonoscopy, supporting the need to account for the cumulative sensitivity of repeated FITs when evaluating the test's efficacy

Identification of small-molecule urea derivatives as PTPC modulators targeting the c subunit of F1/Fo-ATP synthase

Maintaining a high percentage of living and functional cells in those pathologies in which excessive cell death occurs, such as neurodegenerative disorders and cardiovascular diseases, is one of the most intriguing challenges in the field of biochemical research for drug discovery. Here, mitochondrial permeability transition-driven regulated cell death is the main mechanism of mitochondrial impairment and cell fate; this pathway is still lacking of satisfying pharmacological treatments to counteract its becoming; for this reason, it needs continuous and intense research to find new compounds as modulator of the permeability transition pore complex (PTPC) activity. In this study, we report the identification of small-molecule urea derivatives able to inhibit PTPC opening following calcium overload and selected for future use in cytoprotection