Mortality from COVID-19.

Abstract: The differences of the epidemiology (incidence, case-to-death rate, mortality, etc) of COVID-19 between USA and Italy are analyzed taking into account the social, economic and sanitary characteristics of the two countries, both severely hit be the pandemic; and the causes of the so many different behaviors of the disease in each of them are discussed and explained.

Impact of cardiovascular risk factors on incidence and severity of Retinal Vein Occlusion.

PURPOSE: Retinal Vein Occlusion (RVO) is a thrombotic process affecting retinal veins. The purpose of this research is to study demographic characteristics and prevalence of cardiovascular comorbidities among subjects affected by RVO. In addition, authors explore the role of each variable in determining occlusion type and severity. SUBJECTS, MATERIALS AND METHODS: This was a prospective observational study recruiting subjects affected by RVO and secondary macular edema. Exclusion criteria included pre-existing macular edema, recent ocular surgery (<6 months), pregnancy, diagnosis other than RVO, diabetes mellitus type I, any systemic pathology that significantly reduced life expectancy. Each participant was studied through a comprehensive medical history, cardiovascular assessment, blood testing, ocular exam, and macular OCT imaging. RESULTS: A total of 145 eyes, 145 participants, thereof 80 males (55%) and 65 females. (45%) Mean age: 62.5 ± 14.3 SD. 61 eyes (42%) were affected by CRVO and 84 eyes (58%) by BRVO. No statistically significant differences were noted between genders. Hypertension was very prevalent (63%). Dyslipidemia was more associated with BRVO (p = 0.044). Subjects with hypertension had a mean central macular thickness (CMT) of 643 µm against a mean of 489 µm of those without hypertension. (p < 0.05). No other variable was associated with macular edema severity. CONCLUSIONS: Older age and hypertension are strong risk factors for RVO. Dyslipidemia was strongly associated with BRVO. (p=0.044) Hypertension was not only associated with RVO incidence, but also with its severity. In fact, hypertensive subjects had significantly worse macular edema.

Pre-cancerous changes in urothelial endocytic vesicle leakage, fatty acid composition, and As and associated element concentrations after arsenic exposure.

The urothelium covering the luminal surface of the urinary bladder has developed an efficient permeability barrier that protects it against the back-flow of toxins eliminated in the urine. The subapical endocytic vesicles containing the urinary bladder fluid phase are formed during the micturition cycle by endocytosis processes of the superficial cells. In normal conditions, the permeability barrier of the endocytic vesicles blocks the passage of the fluid phase to the cellular cytoplasm and the fluid is recycled to the bladder lumen. The aim of this work was to investigate the alteration of the endocytic vesicle membrane permeability barrier to toxins such as iAs (inorganic arsenic) administered in drinking water. By using an induced endocytosis model and the fluorescence requenching technique, it is shown that the exposure of rats to ingestion of water containing iAs not only induced pre-cancerous morphological changes, but allowed the differential leakage of an endocytosed fluorescent marker, HPTS, and its quencher, DPX, (hydroxypyrene-1,3,6-trisulfonic acid and p-xylene-bis-pyridinium bromide, respectively) out of the vesicular lumen. The leakage of the cationic DPX was almost complete, while the release of the anionic HPTS molecule was partial and higher in arsenic-treated-rats than in controls. Such membrane alteration would allow the toxins to elude the permeability barrier and to leak out of the endocytic vesicles, thus establishing a "bypass" to the permeability barrier. The retention of As in the urinary bladder, assessed by synchrotron radiation X-ray fluorescence spectrometry (SR-µXRF), was lower than the kidney accumulation of arsenic previously observed by our group and was accompanied by altered concentrations of K, Ca, Fe, Cu and Zn, all ions related to cellular metabolism. The results support the hypothesis that low amounts of endocytosed As can accumulate in the interior of the urothelial superficial cells and initiate the cytotoxic effects reflected in the morphological alterations observed.

Antioxidant activity of different extracts of Argentinian medicinal plants against arsenic-induced toxicity in renal cells.

Chronic toxicity of arsenic resulting from drinking water is a health problem encountered in humans, especially in South America and Asia, where a correlation between oxidative stress, tumor promotion, and arsenic exposure has been observed. Differential solvent extraction (petroleum ether (PE); dichloromethane (DCM); methanol (OL) and water (W)) was performed to compare the protective (antioxidant) activity of five Argentinian medicinal plants on arsenite-induced oxidative stress in Vero cells, assayed by hydroperoxide measurement. The results were analyzed using ANOVA followed by the LSD Fisher test. The data showed that arsenite was a pro-oxidant agent which acts in a time-dose-dependent manner. Extracts from Eupatorium buniifolium (PE), Lantana grisebachii (PE, W), Mandevilla pentlandiana (PE, W), and Sebastiania commersoniana (DCM, OL, W) prevented the formation of both aqueous and lipid hydroperoxides, but Heterothalamus alienus only impeded lipid ones. Therefore, antioxidant extracts are potentially beneficial and may have a protective activity against arsenite-induced renal injury. Among these, the aqueous extract of L. grisebachii may represent the most suitable preparation for humans since the traditional usage of this plant in popular medicine is through consumption of tea.

Effects of the plant flavonoids silymarin and quercetin on arsenite-induced oxidative stress in CHO-K1 cells.

Chronic toxic effects of arsenic resulting from drinking water are a human health problem, especially in South-America and Asia. Arsenic is capable of influencing various cellular processes, causing adverse effects, including cancer. Although the exact mechanism of the action is not known, a correlation between oxidative stress, tumour promotion and arsenic exposure has been observed. We examined the effects of silymarin and quercetin, in counteracting oxidative stress produced by acute or sub-chronic sodium arsenite exposure. The stress responses to arsenite included an increase in the heat shock protein 70 kDa expression, lipid peroxidation assayed by conjugated dienes measure, and gamma-glutamyl-transpeptidase activity. We found that all these stress responses were eliminated by silymarin and quercetin in acute experiments. Both flavonoids diminished the conjugated dienes formation during sub-chronic cultures. Our results suggest that these antioxidant flavonoids, which may be easily incorporated into the diet, may afford a protective effect against arsenite-induced cytotoxicity.

Medicinal plants from the "Sierra de Comechingones", Argentina.

Argentina is a country with both rich floral biodiversity and cultural diversity. Traditional herbal medicines are important in the health care of most people, and rely heavily on the use of indigenous plants. An ethnobotanical survey of the "Sierra de Comechingones" made over a 26-year period (1979-2005), indicated that 65 families and 149 different genuses were used in traditional medicines. The use of these medicines was observed to be widespread and prevalent over orthodox medicine. Medicinal native plants from this mountain range make up 31% of the total Argentina medicinal native flora. In addition, there are 15 endemic species that grow only in the region. The botanical name, popular uses, parts utilized, as well as the distribution of these medicinal plants from the "Sierra de Comechingones", Argentina, were summarized. Previous reports on phytochemical and biological activities in relation to cancer, antimicrobials and pesticides were also included.

Effect of the co-administration of phenobarbital, quercetin and mancozeb on nitrosomethylurea-induced pancreatic tumors in rats.

UNLABELLED: We have previously shown that a single i.p. injection of nitrosomethylurea (NMU) in 3-day-old rats orally treated with the pesticide mancozeb (MZ), the flavonoid quercetin (Q) or in combination (MZ-Q) induces hyperplasia, atypical acinar cell proliferation and carcinoma in situ (CIS) in the pancreas. This work studies the effect of oral administration of phenobarbital (PB) on this model of pancreatic carcinogenesis. The animals were fed on a diet supplemented by MZ or/and Q from the 10th day of pregnancy, thorough lactation and as pups after weaning until being sacrificed at week 24. Saline injection with non-supplemented diet was used for the control group (SAL). The experimental groups were (1) SAL (control), (2) SAL-PB, (3) NMU, (4) NMU-PB, (5) MZ-NMU, (6) MZ-NMU-PB, (7) Q-NMU, (8) Q-NMU-PB, (9) MZ-Q-NMU and (10) MZ-Q-NMU-PB. Acinar cell hyperplasia was found in all groups of NMU-treated rats. Dysplastic foci (DYS) were seen in groups 3-10 at the following percentages: 19, 48, 71, 27, 71, 35, 100 and 30, respectively. CIS were recorded in groups 4 to 10 at percentages: 4, 36, 13, 11, 0, 16, 5, respectively. CONCLUSION: Although PB, Q or MZ given alone enhance DYS lesions in NMU-treated rats, the MZ/Q/PB combined treatments may increase (mainly in males) or decrease (mainly in female) the DYS and CIS proportion. Because PB, MZ and Q influence P450 enzymes, we suggest that these enzymes play a role in the carcinogenesis process.

Intrinsic excitonic luminescence in odd and even numbered oligothiophenes.

The emission properties of crystalline oligothiophenes (OTs) are investigated and related to the different selection rules arising from the number of rings. In odd OT crystals the purely electronic emission is absent since the molecular A1-1B(1) transition dipoles cancel at the bottom of the excitonic band. On the contrary, in crystals of even OTs this transition is allowed due to the constructive interference of the off-axis components of the molecular transition dipole. It possesses a polarization in the herringbone plane and exhibits superradiant behavior.

High-temperature ultrafast polariton parametric amplification in semiconductor microcavities.

Cavity polaritons, the elementary optical excitations of semiconductor microcavities, may be understood as a superposition of excitons and cavity photons. Owing to their composite nature, these bosonic particles have a distinct optical response, at the same time very fast and highly nonlinear. Very efficient light amplification due to polariton-polariton parametric scattering has recently been reported in semiconductor microcavities at liquid-helium temperatures. Here we demonstrate polariton parametric amplification up to 120 K in GaAlAs-based microcavities and up to 220 K in CdTe-based microcavities. We show that the cut-off temperature for the amplification is ultimately determined by the binding energy of the exciton. A 5-micrometer-thick planar microcavity can amplify a weak light pulse more than 5,000 times. The effective gain coefficient of an equivalent homogeneous medium would be 107 cm-1. The subpicosecond duration and high efficiency of the amplification could be exploited for high-repetition all-optical microscopic switches and amplifiers. 105 polaritons occupy the same quantum state during the amplification, realizing a dynamical condensate of strongly interacting bosons which can be studied at high temperature.

Ultrafast formation of nonemissive species via intermolecular interaction in single crystals of conjugated molecules.

We investigate the influence of interchain interactions on the photoluminescence processes in a sexithiophene single crystal by applying hydrostatic pressure. We perform transient photoluminescence spectroscopy in the time domain of 100 fs for pressures up to 60 kbar. The combined use of steady-state and time-resolved optical spectroscopies allows us to show that the pressure-induced quenching of the photoluminescence is caused by an ultrafast (approximately 100 fs) formation of intermolecular species.

Crossover from exciton to biexciton polaritons in semiconductor microcavities

Pump-probe measurements in a microcavity containing a quantum well show that a population of circularly polarized ( sigma(+)) excitons can completely inhibit the transition to sigma(-) one-exciton states by transferring the oscillator strength to the biexcitonic resonance. With increasing pump intensity the linear exciton-polariton doublet evolves into a triplet polariton structure and finally into a shifted biexciton-polariton doublet. A theoretical model of interacting excitons demonstrates that the crossover from exciton to biexciton polaritons is driven by three-exciton Coulomb correlation.

The cytoskeletal components of the myelin fraction are affected by a single intracranial injection of apotransferrin in young rats.

We have previously shown that in rat pups intracranially injected with a single dose of apotransferrin (aTf), there is an early oligodendroglial cell OLGc differentiation. The expression of the mRNAs of myelin basic proteins and of 2',3' cyclic nucleotide 3'-phosphodiesterase and the amount of the corresponding proteins, as well as myelin glycolipids and phospholipids, were significantly increased in these animals at 10 and 17 days of age. Microtubules and myelin basic proteins appear to be closely associated in OLGc and it has been shown that the mRNAs of myelin basic proteins are concentrated in the OLGc processes. The aim of this work was to clarify if the accelerated myelination produced by aTf could be linked to changes in certain cytoskeletal elements present in the myelin fraction such as tubulin, actin, and different microtubule-associated proteins (MAPs). A significant increase in the expression of the mRNA of tubulin and actin was observed in the brain of the aTf-treated animals. Several MAPs, particularly MAP 1B and stable tubule only peptide as well as actin and tubulin, were markedly increased in the Triton X-100 insoluble pellet obtained from the myelin fraction of these animals. The changes that we have previously described in the myelin of aTf intracranially injected rats, could be the consequence of its action on the cytoskeletal network of the OLGc. An enlargement of this structure would result in a more efficient and faster movement of the different components that are normally transported to the myelin by the cytoskeleton of this cell.

Post-translational arginylation of proteins in cultured cells.

The aim of this study was to analyze the N-terminal post-translational incorporation of arginine into cytosolic proteins from cultured cells and the in vitro incorporation of arginine into soluble proteins of PC12 cells after serum deprivation. Arginine incorporation was measured in the presence of protein synthesis inhibitors. None of the inhibitors used affected significantly the arginylation reaction while the novo synthesis of protein was reduced by 98%. Under these conditions, we found that of the total [14C]arginine incorporated into the proteins, around 20% to 40% was incorporated into the N-terminal position of soluble proteins by a post-translational mechanism. These results suggest that this post-translational aminoacylation may be a widespread reaction in neuronal and non-neuronal cells. We also found that in PC12 cells, the in vitro post-translational arginylation was 60% higher in apoptotic cells with respect to control cells. These findings suggest that the post-translational arginylation of proteins may be involved in programmed cell death.

Posttranslational arginylation of soluble rat brain proteins after whole body hyperthermia.

We have previously reported the posttranslational addition of [14C]-arginine in the N-terminus of several soluble rat brain proteins. One of these proteins was identified as the microtubule-associated protein, the stable tubule only polypeptide (STOP). However, despite the fact that the biological significance of arginylation is not completely understood, some evidence associates it with proteolysis via the ubiquitin pathway. Since this degradative via is exacerbated as a response to stress, we studied in vitro the posttranslational [14C]-arginylation of cytosolic brain proteins of rats subjected to hyperthermia in vivo. Immediately after subjecting the animals to hyperthermia, a minor reduction (16%) in the acceptor capacity of [14C]-arginine into proteins was observed in comparison with animals maintained at 28 degrees C. However, in the animals allowed to recover for 3 h, an increase (46%) in the arginylation was observed concomitantly with a significant accumulation of the heat shock protein (70 kDa; hsp 70) when compared to the control animals. These findings suggest that the posttranslational arginylation of proteins participate in the heat shock response. The STOP protein of the soluble brain fraction of control animals, which in Western blot appears as a doublet band (125 and 130 kDa, respectively), is seen, after the hyperthermic treatment, as a single band of 125 kDa. The amount of 125 kDa protein, as well as the in vitro incorporation of [14C]-arginine, increases after hyperthermia in comparison with control animals. Following hyperthermic treatment, we observed a decrease in the amount of in vivo [35S]-methionine-labeled brain proteins. We speculate that, as observed for STOP protein, the increase in the degradation of protein that occurs in hyperthermia, would produce an increase in the amount of arginine acceptor proteins.

Posttranslational arginylation of brain proteins.

The knowledge of brain protein metabolism is important in understanding nervous system brain function. Protein synthesis rates are high in young brain, decline rapidly at adult stages, and thereafter continue falling slowly with age. The breakdown of protein appears to follow a similar rate (1). Protein synthesis and degradation however, are only the two extremes of a complex phenomena which includes a variety of other protein modifications. Proteolytic cleavage is the most common covalent modification of proteins; probably all proteins that have been isolated were modified by proteolysis, since only few are found with the starting amino acid (methionine) attached. This suggests that most proteins were subject to one or more co- and/or posttranslational modifications (2). One of these posttranslational modifications is the arginylation of proteins, described 30 years ago, which now is being recognized as a widespread modification of proteins. In this review, the current status of posttranslational arginylation of brain proteins is discussed.

'Direct' and 'crossed' modulation of human motor cortex excitability following exercise.

Rapid repetitive movements of the thumb (1 min duration) produce a reversible decrease in the activated primary motor cortex (MI) excitability to transcranial magnetic stimulation (TMS) with recovery within 35-40 min. In the present study we investigated (1) the role of peripheral sensory feedback in inducing such decrease and (2) possible effects of exercise on the non-activated MI. Stimulation of peripheral Ia afferent fibres, induced by 1 min vibration of thenar muscles and 2 Hz electrical stimulation of the median nerve at the wrist, have no effect on motor evoked potential (MEP) amplitude to TMS suggesting no role for sensory feedback to produce MI excitability modulation. Exercise produces a significant (P < 0.01) decrease of MEPs for homologous non-exercised muscles with concomitant contraction of corresponding motor cortical output maps, suggesting that changes in MI excitability also occur in the nonactivated hemisphere. This 'crossed' effect might relate to an interhemispheric transfer of information, via homotopic connections of the corpus callosum.

The post-translational incorporation of arginine into a beta-amyloid peptide increases the probability of alpha-helix formation.

The beta-amyloid peptide (beta AP1-40) inhibited the in vitro post-translational incorporation of [14C]arginine at the N-terminus of brain soluble proteins and was labelled by the incorporation of [14C]arginine. Addition of arginine at the N-terminal position of beta AP1-40 is predicted to increase the probability of an alpha-helix structure being formed on the first residues with a higher hydrophilic characteristic, increasing the possibility of these residues being exposed to the aqueous environment. Unmodified beta AP1-40 has a low alpha-helix content and a higher probability of beta-turn formation. Accumulation of beta AP1-40 in Alzheimer's disease may therefore be due to a reduced arginylation reaction and consequently to a decrease in its normal degradation by the ubiquitin pathway.

Some common properties between a brain protein that is modified by posttranslational arginylation and the microtubule-associated STOP protein.

Properties so far studied of the 125-kDa 14C-arginylated protein from rat brain show remarkable similarities with those of the STOP (stable tubule only polypeptide) protein. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis the 125-kDa 14C-arginylated protein moves to the same position as the STOP protein. The 125-kDa 14C-arginylated protein was immunoprecipitated by the monoclonal Mab 296 antibody specific for neuronal STOP protein. The 125-kDa 14C-arginylated protein was retained by a calmodulin column like STOP protein. As occurs with the STOP protein, the 125-kDa 14C-arginylated protein is found in higher proportion in cold-stable than in cold-labile microtubules. However, the modified protein associates with microtubules in a lower proportion than the STOP protein. We conclude that the STOP protein incorporates arginine by a posttranslational reaction but that only a small fraction of the STOP protein shows acceptor capacity in vitro.

Cortical output modulation after rapid repetitive movements.

Transcranial magnetic stimulation was used to evaluate changes in motor cortex excitability after rapid repetitive movements in five healthy subjects aged 23-30 years, by considering the amplitude of motor evoked potentials (MEPs) at rest and after one minute of maximal frequency repetitive abduction-adduction movements of the thumb. In addition, M and F waves were evaluated by stimulating the median nerve at the wrist. All of the examined subjects showed a clear modification in post-exercise MEP amplitudes, with a mean maximal reduction of 50-60% in comparison with basal values and complete recovery after a period of about 35 minutes. The time course of this phenomenon showed a triphasic pattern: (I) a rapid decrease phase up to the fifth minute; (II) a maximal depression phase for a period of about ten minutes; (III) a slow return to basal values. No significant changes were observed in post-exercise M and F waves. These results show the existence of a reversible modulation of the excitability of the upper motor neuron after rapid repetitive movements. It is likely that this modulation takes place at the level of the motor cortex and that its anatomo-functional substrate is represented by the activation of inhibitory intracortical circuits.

Statutory requirements for disclosure of breast cancer treatment alternatives.

Therapeutic options for breast cancer, particularly for early-stage disease, and increased patient participation in medical decision-making have oriented state legislatures toward ensuring that women with breast cancer have adequate information about treatment alternatives. Currently, 18 states have enacted statutes regarding physician disclosure of treatment alternatives to breast cancer patients. This paper reviews these statutes in the context of the requirements imposed on the physician as health care provider and the content of medical information presented to the patient as a consequence of the laws. State statutes were identified through the National Cancer Institute's State Cancer Legislative Database, and the statutory requirements were analyzed. For statutes requiring development of a written summary of treatment alternatives, the most recent summary was obtained through the responsible state agency, and informational content was analyzed for relevance to treatment decisions in early-stage disease. As a group, these laws address informed consent for treatment, physician behavior within the patient-physician relationship, and the medical information upon which treatment decisions are based. Individual statutes vary in the scope of the issues addressed, particularly in the responsibility placed on physicians, and treatment option summaries developed in response to this legislation vary widely in content and scope. Despite broad implications of these statutes in oncology practice, little is known about their effects on breast cancer care. Additional research is needed to define the impact of these statutes on breast cancer care, as such legislation is considered by other states for this and other diseases.