Cranial osteology and paleoneurology of Tarjadia ruthae: An erpetosuchid pseudosuchian from the Triassic Chañares Formation (late Ladinian-?early Carnian) of Argentina.

Tarjadia ruthae is a quadrupedal terrestrial pseudosuchian from the Middle-early Upper Triassic of the Chañares Formation, La Rioja Province, Argentina. Originally, this species was identified as an indeterminate archosaur and later as a doswelliid archosauriform based on very fragmentary specimens characterized by the ornamentation of the skull roof and osteoderms. Additional specimens (including skulls and postcrania) recovered in the last decade show that Tarjadia is an erpetosuchid, an enigmatic pseudosuchian group composed of six species registered in Middle-Upper Triassic continental units of Tanzania, Germany, Scotland, North America, Brazil, and Argentina. Tarjadia ruthae from Argentina and Parringtonia gracilis from Tanzania are the best preserved and more abundant species. Although the monophyly of Erpetosuchidae is well supported, alternative high-level positions within Archosauria have been suggested, such as sister taxon to Crocodylomorpha, Aetosauria, or Ornithosuchidae. In order to improve the knowledge about the erpetosuchids, we performed a detailed description and paleoneurological reconstruction of the skull of Tarjadia ruthae, based on two articulated partial skulls (CRILAR-Pv 478 and CRILAR-Pv 495) and other fragmentary specimens. We analyzed the stratigraphic and geographic occurrence of historical and new specimens of Tarjadia and provided a new emended diagnosis (the same for the genus as for the species, due to monotypy) along with a comparative description of the cranial endocast. The skull of Tarjadia is robust, with a thick and strongly ornamented skull roof, triangular in dorsal view, with concave lateral margins at mid-length that form an abrupt widened posterior region. The external nares are the smallest openings of the skull. The antorbital fossa is deeply excavated and has a small heart-shaped fenestra with both lobes pointing anteriorly. The supratemporal fenestrae are as large and rounded as the orbits, and the infratemporal fenestrae are L-shaped with an extensive excavation along the jugal, quadratojugal and quadrate. The hemimandibles are low, slightly concave on the dentigerous region and strongly convex on the posterior region, conferring them a S-shaped profile in dorsal view. The external mandibular fenestra is small and elliptic, being twice longer than high. The maxillary dentition is restricted to the anterior to mid region of the rostrum. Since the braincase of both specimens is partially damaged, the dorsal surface of the brain could not be entirely reconstructed. As a result, the endocast is anteroposteriorly elongated and seemingly flat, and the cephalic flexure seems to be lower than expected for a suchian. The labyrinth is twice wider than high, the semicircular canals are remarkably straight, and the anterior canal is longer than the posterior one.

Transcranial brain photoplethysmography to study the venules of cerebral cortex in patients with multiple sclerosis.

OBJECTIVE: To evaluate the utility of a transcranial brain photoplethysmography parameter as a potential marker for patients with multiple sclerosis. METHODS: We investigated 38 patients affected by multiple sclerosis, according to the revised McDonald criteria (12 males and 26 females, mean age 41.1 ± 8.5 years, Expanded Disability Status Scale mean value 2.6 ± 2.1) and compared them with 20 age- and sex-matched healthy controls. By means of transcranial brain photoplethysmography, a safe and non-invasive technology, we measured the increase in cerebral blood volume during compression for 10 s of the internal jugular veins of both sides in sitting position. RESULTS: The cerebral blood volume increase was significantly smaller in the multiple sclerosis patients (left frontal cortex: -58%, p < 0.0001; right frontal cortex: -59%, p < 0.0001) compared with the controls. CONCLUSIONS: Our study reveals that a minor increase in cerebral blood volume on the frontal cortex of both sides in sitting position is associated with a diagnosis of multiple sclerosis and might be a new marker.

The increased distensibility of the wall of cerebral arterial network may play a role in the pathogenic mechanism of migraine headache.

The aim was to evaluate whether patients with episodic migraine with (MA+) and without aura (MA-), during the interictal period of migraine would have an altered distensibility of the wall of cerebral arterial network and whether it would play a role in migraine headache. To evaluate the distensibility of the wall of cerebral arterial network, we measured the time-delay in milliseconds (ms) between the R-wave of an electrocardiogram and the arterial pulse wave of cerebral microcirculation (R-APWCMtd) on the frontal cortex detected by near-infrared spectroscopy (NIRS) in 10 patients with MA+ (age 39.5 ± 12.2 years), in 10 with MA- (age 40.3 ± 10.2 years), according to ICHD-3 criteria 2012, during the interictal period of migraine, and in 15 age-, sex- and height-matched healthy control subjects. The patients with migraine had a significantly longer R-APWCMtd than the control subjects F = 13.4, p < 0.001: MA+:+38.3 ms; MA-:+34.7 ms indicating an increased distensibility of the wall of cerebral arterial network. In multiple regression analysis, R-APWCMtd was significantly associated with migraine (R (2) = 0.50, p < 0.0001) but not with age, gender, height, migraine attack frequency and disease duration. The increased distensibility leads to an increased flow pulsatility into intracranial dural meningeal vessels that may lead to a mechanical stimulation of the nociceptors that innervate the dural vasculature. This condition may play a role in promoting the sensitization of trigeminovascular afferents and sterile inflammation within the dura mater that are fundamental to the pathogenesis of migraine headache.

New brain reperfusion rehabilitation therapy improves cognitive impairment in mild Alzheimer's disease: a prospective, controlled, open-label 12-month study with NIRS correlates.

BACKGROUND AND AIMS: A large body of evidence indicates that cerebral hypoperfusion is one of the earliest signs in the development of Alzheimer's disease (AD). The aim of our study was to evaluate whether the brain reperfusion rehabilitation therapy (BRRT) would improve verbal memory and learning and/or global cognitive impairment in mild AD. METHODS: Using a prospective, controlled, open-label 12-month study, we enrolled 15 patients with mild AD, who underwent BRRT program (BRRT group), and 10 age-sex-matched mild AD patients, who received no treatment (control group). At baseline (T0), and at the end of the 3 months (T3), 6 months (T6) and 12 months (T12) participants from both groups were given an evaluation, using Mini-Mental State Examination (MMSE) and Rey Auditory Verbal Learning Test (RAVLT). In both groups by using near-infrared spectroscopy, at T0 and T12, we measured tissue oxygen saturation (TOI) on temporal-parietal and frontal cortex of both sides. RESULTS: Ten patients from the BRRT group and 10 from the control group completed the 12-month follow-up. At the end of rehabilitation protocol, a significant improvement of MMSE and RAVLT was observed in the BRRT group as compared to control group. At T12 compared to T0, a significant improvement of TOI on frontal cortex of both sides was observed in the BRRT group as compared to control group. CONCLUSION: BRRT improves verbal memory-learning and global cognitive impairment which are associated with increased TOI values on frontal cortex of both sides.

Ascertainment bias in dementias: a secondary to tertiary centre analysis in Central Italy and conceptual review.

BACKGROUND AND AIMS: Ascertainment bias (AB) indicates a bias of an evaluation centre in estimating the prevalence/incidence of a disease due to the specific expertise of the centre. The aim of our study was to evaluate classification of different types of dementia in new cases appearing in secondary and tertiary centres, in order to evidence possible occurrence of AB in the various (secondary to tertiary) dementia centres. METHODS: To assess the mechanism of AB, the rates of new cases of the different forms of dementia reported by different centres were compared. The centres involved in the study were 11 hospital-based centres including a tertiary centre, located in the University Department of Clinical Neurology. The tertiary centre is endowed with state-of-the-art diagnostic facilities and its scientific production is prominently focused on dementia with Lewy bodies (DLB) thus suggesting the possible occurrence of a bias. Four main categories of dementia were identified: Alzheimer's disease (AD), DLB, fronto-temporal dementia (FTD), vascular dementia (VaD), with other forms in a category apart. The classification rate of new cases of dementia in the tertiary centre was compared with rates reported by secondary centres and rates of recoding were calculated during a follow-up of 2 years. RESULTS: The study classified 2,042 newly diagnosed cases of dementia in a population of 1,370,000 inhabitants of which 315,000 were older than 65. AD was categorized in 48-52 % of cases, DLB in 25-28 %, FTD in 2-4 % and VaD in 17-28 %. During the 2-year follow-up the diagnosis was re-classified in 40 patients (3 %). The rate of recoding was 5 % in the tertiary centre, 2-8 % in referrals from secondary to tertiary centre, 2-10 % in recodings performed in secondary centres and addressed to tertiary centre. Recoding or percentages of new cases of AD or DLB were not different in the comparison between secondary or between secondary and tertiary centres. FTD and VaD were instead significantly recoded. CONCLUSION: The results of the study suggest that in a homogeneous area, AB is not interfering with diagnosis of AD or DLB.

A new near-infrared spectroscopy parameter as marker for patients with migraine.

Due to the lack of markers for migraine, diagnosis relies entirely on symptomatology. The aim is to evaluate the utility of a new near-infrared spectroscopy parameter as potential marker for patients with episodic migraine with (MA+) and without aura (MA-) during the interictal period of migraine. We studied 10 patients with MA+ (age 39.5 ± 12.2 years) and 10 with MA- (age 40.3 ± 10.2 years), according to ICHD-II criteria 2004, during the interictal period of migraine and 15 age and sex matched healthy control subjects. The cases and controls were free from vascular risk factors and migraine prophylactic medications. At rest in all the participants, the time delay in millisecond (ms), between the R-wave of an electrocardiogram and the arterial pulse wave of cerebral microcirculation detected by transcranial near-infrared Spectroscopy (R-APWCMtd) on the frontal cortex of both side, was determined. The patients with migraine had a significantly longer R-APWCMtd than the control subjects: the patients with MA+: +38.3 ms, p < 0.0002; the patients with MA-: +34.7 ms, p < 0.0002, and there was no significant difference between MA+ and MA-, p = 0.71. We used receiver-operator characteristic (ROC) curve to assess the diagnostic potential of the R-APWCMtd measurement for diagnosis of migraine; we found an ROC area of 0.92, p < 0.0001, sensitivity 77.8 %, specificity 100 % and cutoff of 242 ms. Our study seems to indicate that the longer R-APWCMtd is independently associated with a diagnosis of migraine, and may be considered a new marker for migraine, especially in patients with MA+.

Tissue oxygen saturation and pulsatility index as markers for amnestic mild cognitive impairment: NIRS and TCD study.

OBJECTIVE: To evaluate the utility of near-infrared spectroscopy (NIRS) and transcranial Doppler (TCD) parameters as potential markers for amnestic mild cognitive impairment (aMCI). METHODS: By means of NIRS and TCD, noninvasive and inexpensive technologies, we studied 21 patients with aMCI (10 M and 11 F, 70.2 ± 7.3 years) and 10 age matched healthy controls. RESULTS: By means of NIRS, we found a significant mean decrease of tissue oxygen saturation of cortex microcirculation (TOI), - 27%, p < 0.0005, on the temporal-parietal cortex of both side compared to the controls. By means of TCD, we found a significant mean increase of pulsatility index (PI), p < 0.0007, of middle cerebral artery (MCA) of both side compared to the controls. Cerebrovascular risk factors were present in 81% of the aMCI patients. CONCLUSIONS: Our study reveals that the TOI reduction on the temporal-parietal cortex of both side and the increase of PI in both MCA are associated with a clinical diagnosis of aMCI patients. SIGNIFICANCE: The reduction of TOI may be considered a new marker for aMCI, especially when combined with the increase of PI in MCA.

Stroke risk and migraine: near-infrared spectroscopy study.

Migraine has been associated with an increased risk for ischemic stroke. A recent study suggests that a generalized peripheral vasoconstriction may represent one possible mechanism underlying the increased risk for ischemic stroke. The aim is to verify the presence of cerebral arteriolar vasoconstriction during the interictal period of migraine with (MA+) and without aura (MA-). We studied 10 patients with MA+ (age 39.5 ± 12.2 years), 10 with MA- (age 40.3 ± 10.2 years), according to ICHD-II criteria 2004, during the interictal period of migraine, and 15 age- and sex-matched healthy control subjects. At rest in all the participants, the time-delay in millisecond (ms), between the R-wave of an electrocardiogram and the arterial pulse wave of cerebral microcirculation detected by transcranial near-infrared spectroscopy (R-APWCMtd) on the frontal cortex of both side, was determined to evaluate the presence of cerebral arteriolar vasoconstriction. The patients with migraine had a significantly longer R-APWCMtd than the control subjects: the patients with MA+: +38.3 ms, p < 0.0002; the patients with MA-: +34.7 ms, p < 0.0002. Our study seems to indicate that the migraine is independently associated with a mild vasoconstriction of cerebral arterioles that may represent one possible mechanism underlying the increased stroke risk especially in patients with MA+.

Correlation between the arterial pulse wave of the cerebral microcirculation and CBF during breath holding and hyperventilation in human.

OBJECTIVE: To evaluate if relative changes in the amplitude of the arterial pulse wave of the cerebral microcirculation (APWCM) measured by near-infrared spectroscopy (NIRS) may provide information about relative changes of cerebral blood flow (CBF) in cerebral cortex. METHODS: In 10 healthy human volunteers, through simultaneous recording of the APWCM amplitude by means of NIRS and the mean blood flow velocity (MBFV) of middle cerebral artery by means of transcranial Doppler (TCD) at rest and during breath holding and hyperventilation, we evaluate a possible correlation between relative changes of the mean APWCM amplitude and relative changes of MBFV. RESULTS: We found a significant linear correlation: breath holding: R(2) 0.84, p < 0.001, hyperventilation: R(2) 0.81, p<0.001. CONCLUSION: The relative changes of the mean APWCM amplitude seem able to provide information about relative changes of CBF of cerebral cortex in healthy adult humans during breath holding and hyperventilation. SIGNIFICANCE: APWCM detected by NIRS, a safe, repeatable, inexpensive technology and at the bedside may improve the study of cerebral cortex microcirculation in neurological diseases.

Pathophysiology of migraine attack with prolonged aura revealed by transcranial Doppler and near infrared spectroscopy.

The aim of this study is to identify the pathophysiology of migraine attack with prolonged aura (between 1 h and 7 days) not clearly understood. We studied cortical cerebral microcirculation by an innovative near infrared spectroscopy system (NIRS) and cerebral macrocirculation by transcranial Doppler (TCD) in eight subjects (3 M and 5 F, age range 21-41 years) during spontaneous prolonged migraine aura and after 1, 2, 4, 6, 12 and 24 h since the end of aura and compared the results with the headache-free periods. During aura NIRS showed a significant decrease of the arterial pulse wave of cerebral microcirculation (APWCM) amplitude (-35%), p < 0.002, and an increase of cerebral tissue oxygen saturation (SctO(2)) (+15%), p < 0.008 ipsilateral to the headache pain and contralateral to the symptoms of aura compared with the headache-free periods; TCD showed a significant increase of pulsatility index (+38%), p < 0.001 and a significant decrease of the diastolic velocity in the posterior and middle cerebral artery ipsilateral to the headache pain and contralateral to the symptoms of aura compared with the headache-free periods. During prolonged migraine aura we found areas of cortical hypoperfusion corresponding to the topography of aura symptoms that were the result of a decreased metabolic demand rather than ischemic mechanism.

Behavior profile of family members of donors and nondonors of organs.

UNLABELLED: Organ transplant shortage is a global problem caused by several factors, most of which are related to members of the family, who play a major role in the donation process. OBJECTIVE: We sought to determine the most determinant features in the donor profile that relate to positive decisions versus refusal of donation. MATERIAL AND METHODS: Fifty-six families who were approached by the Organ Procurement Organization (OPO) from November 2004 to April 2006 agreed to participate in this work. To assess donor profiles, we used a structured interview. RESULTS: Parental involvement directly in decisions about donation lead to significantly less frequent consent (P = .005), young donor age was associated with a reduced probability of donation (P = .002), violent death negatively influenced donation consent, excluding suicide (P = .004). CONCLUSION: The present study showed violent death, young patient age, and parental donation consent to be the most important factors that make it harder to obtain consent organ donation. When a collateral relative (sibling/uncle) or children were responsible for the donation decision, there was more success of consent.

Prophylactic donor tricuspid annuloplasty in orthotopic bicaval heart transplantation.

OBJECTIVE: The objective of this study was to evaluate the effects of prophylactic heart donor tricuspid annuloplasty to improve the degree of valvar regurgitation and the hemodynamic performance after orthotopic heart transplantation using bicaval anastomosis. METHODS: From March 1985 to December 2005, of the 368 patients undergoing orthotopic heart transplantation, 20 patients were selected because they survived more than 6 months. They were divided into 2 groups: group I-10 patients underwent prophylactic heart donor tricuspid annuloplasty by the De Vega technique; group II-10 patients did not receive a graft with this procedure. Their presurgical clinical characteristics were the same. In the postsurgical period, tricuspid regurgitation degree evaluated by transthoracic Doppler echocardiography was qualified from 0 to 3: 0 = absent; 1 = mild; 2 = moderate; and 3 = severe. Myocardial performance was evaluated by the ventricular ejection fraction and by an invasive hemodynamic study, performed during routine endomyocardial biopsies. RESULTS: At a follow-up of 14.6 +/- 4.3 months (6 and 16 months), group I showed no mortality, whereas group II had 10% (P > .05). However, it was not related to the annuloplasty. The mean degree of tricuspid regurgitation in group I was 0.4 +/- 0.6; in group II, 1.6 +/- 0.8 (P < .05). There was a significant difference between the 2 groups in the right atrium pressure, which was higher in group II. CONCLUSIONS: Prophylactic tricuspid annuloplasty in the heart donor significantly reduced the degree of valvular regurgitation after heart transplantation using a bicaval anastomosis without significantly interfering with the hemodynamic performance of the allograft.

Later evolution after cardiac transplantation in Chagas' disease.

OBJECTIVE: This research reported the accumulated experience with cardiac transplantation in Chagas' disease, emphasizing reactivation, immunosuppression, and mortality. METHODS: Fifty-nine patients undergoing cardiac transplantation had Chagas' disease with classically accepted recipient selection criteria. In this series, 84.7% of the patients were functional class IV; 36.0% used vasopressor support; and 13.5% mechanical circulatory assistance. One patient received a heart and kidney transplantation. RESULTS: After the initial experience the doses of immunosuppressants were significantly reduced with improvement in outcomes. The diagnosis of the reactivation of disease was documented by the identification of parasite in the myocardium, or on subcutaneous or serological exams. Reactivation of disease was significantly reduced by decreasing the immunosuppression. Immediate mortality occurred in 10 cases: three infections, two allograft dysfunction, two rejections, and two sudden deaths. Subsequent mortality happened in 14 patients: four by lymphoma, three by infection, two by Kaposi's sarcoma two by rejection, two by constrictive pericarditis, and one by reactivation of disease in the brain. CONCLUSIONS: There's no correlation between the disease and pre- or postoperative prophylaxis. The early diagnosis and specific treatment of reactivation did not leave functional sequelae in the myocardium. Reduction in immunosuppression significantly reduced reactivation of disease and neoplasms. The combined transplantation can be realized safely with more care about the immunosuppressants.

Complexity and dynamics of HIV-1 quasispecies.

The human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins mediate virus entry into target cells by binding receptors of the cell membrane and fusing viral and cellular structures. In particular, recent crystallographic studies have clarified the complex role of the glycoprotein gp120 in the early phase of the infection. In this context the inter- and intra-host variability of the HIV-1 gp120 poses a major problem for the development of effective methods of immunization against this virus. In the present report, the relevant aspects emerging from the study of HIV-1 variability are addressed and several methodological approaches to evaluate HIV-1 diversity discussed.

Addition of bismuth subnitrate to omeprazole plus amoxycillin improves eradication of Helicobacter pylori.

OBJECTIVE: To evaluate whether the addition of bismuth subnitrate to a dual oral therapy regimen with omeprazole plus amoxycillin could improve Helicobacter pylori eradication. METHODS: Fifty consecutive Helicobacter pylori-positive patients were randomly enrolled to receive either (A) bismuth subnitrate (300 mg q.d.s.), omeprazole (20 mg b.d.) and amoxycillin (500 mg q.d.s.), or (B) omeprazole (20 mg b.d.) and amoxycillin (500 mg q.d.s.). Both groups (n=25 each) received the medication for 14 days. H. pylori status was reassessed 30 days after completion of the therapy in order to evaluate eradication rates. RESULTS: Six patients were lost to follow-up and therefore excluded from the study (three patients from each group). One patient from Group B withdrew from the study because of side-effects. The addition of bismuth subnitrate to omeprazole and amoxycillin significantly improved its efficacy in eradicating H. pylori, with 72% (18/25) eradication in Group A and 52% (13/25) in Group B (P=0.027). The addition of bismuth subnitrate to dual oral therapy was also capable of improving the healing of peptic ulcers when compared with dual oral therapy alone (100%, 8/8 vs. 58%, 4/7; P=0.021). CONCLUSION: Our results demonstrate that the addition of bismuth subnitrate to dual oral therapy enhances H. pylori eradication, and improves healing of peptic ulcers.