Fatal Viral and Bacterial Septicemia in a Seventeen-Year-Old Woman with Immunodepressive Influenza A H1N1: An Autopsy Case.

Abstract: The Influenza A H1N1 subtype can present with a wide spectrum of severity, from mild symptoms of influenza to severe respiratory distress. The morbidity and mortality connected to influenza are mostly associated with secondary bacterial infections. The influenza syndrome alone can cause a massive release of cytokines with dysregulation of the immune system, and it can act in synergy with other bacteria which can enhance cytokines secretion. This article deals with a case of severe pneumonia of H1N1 in a 17-year-old woman with bacterial superinfection with Staphylococcus aureus characterized by a high level of interleukine-6 (105900 pg/mL) and the appearance of severe leukopenia with immuno-suppression, such that HIV infection and hematological diseases were included in the initial differential diagnosis. After death, the autopsy confirmed the presence of severe pneumonia, in addition to an hepatic steatosis in absence of other risk factors. This case reports the rapid and lethal course of influenza A /H1N1 in a young and healthy subject without comorbidities, in an age group in which mortality is about 0.3 deaths per 100,000. The case underlines the importance of quickly diagnosis of viral infections and the differential diagnoses with other immunosuppressive diseases, which can be fatal even in adolescent and healthy subjects.

Medical ethics questions of COVID-19 vaccination in pregnant and lactating women in East Asia and Oceania.

Abstract: We aimed to investigate some of the medical ethics issues that characterize the COVID-19 vaccination phase in pregnancy and breast-feeding. A literature search was conducted using PubMed, Scopus, Web of Science, focusing mainly on the countries of East Asia and Oceania. Vaccination during pregnancy and breastfeeding appears to help protect babies from COVID-19 by enabling antibodies to pass from mother to baby. However, individual countries of the same continent may adopt conflicting policy positions. Not only that, indications on the type of vaccine sometimes vary, depending on whether a woman is pregnant or breastfeeding. In this review we have taken into considerationp the policy positions on pregnancy and lactation by country and type of Covid-19 vaccine in East Asia and Oceania. Ten out of the 18 countries considered (representing more than two thirds of the population of East Asia and Oceania) provide different vaccine indications for pregnant and breastfeeding women. Can this diversity of recommendations be seen as a form of optimal protection for women in these categories, or does it suggest that some countries have taken a defensive position to avoid compensation claims in the event of complications? Is it ethically correct to leave questions concerning informed consent open? Misin-formation during a health crisis leaves people without protection and with increased vaccine hesitancy, especially for vulnerable populations in hard-to-reach areas of East Asia and Oceania.

Letter to the editor in response to "Is it time for international guidelines on physical restraint in psychiatric patients?"

The Mastrogiovanni case was a revolutionary case in the field of Italian forensic psychiatry. A recent judgment of the Court of Cassation has defined what the legal limits of mechanical restraint should be. On the other hand, even today, there is a gap in the scientific community about the presence of guidelines governing mechanical restraint. It is probably time to create specific guidelines to protect the psychiatric patient and the mental health worker.

Cradles of industry and occupational medicine in the modern world: Milan 1906 -- Annus Mirabilis.

BACKGROUND: The example examined is Milan, Italy's main industrial city, where the great International Exhibition was held in 1906. This was the culmination of a period of accelerated industrial growth that modern-day historiography considers to be when Italy's first real industrial revolution began. The twenty-five years between the National Industrial Exhibition of 1881, which was also held in Milan, and the 1906 Exhibition truly reflected a period which was crucial for this transformation to take of. Alongside industry, which was then going through a phase of reorganization and development, Milanese civil society was increasingly turning its interest and attention to what was called the "social question". In an atmosphere of debate and exchange of ideas and experience with Turin, another major industrial city of the north and the birthplace of the Italian engineering and automobile industries, social organizations, political parties and trade unions began to be established thus heralding the Italian approach towards twentieth-century welfare. RESULTS: This is the context in which the first International Congress on Occupational Diseases was held in Milan from 9 to 14 June 1906 within the framework of the International Exhibition. The success achieved with this initiative. organized by Luigi Devoto and Malachia De Cristoforis, which was to continue with the founding of the International Permanent Commission on Occupational Health, showed that the time was ripe for a new subject to appear on the scene--the occupational health physician--who from then on was to play an important role in the promotion of workers' health. CONCLUSIONS: The article outlines the main features of the Italian industrial transformation at the turn of the new century with special attention focused on Milan, the capital of industry in Italy. It also describes the impact on public opinion caused by the events surrounding the epic construction of the transalpine railway tunnels which began in 1856 with the Mont Cenis tunnel, then the tragic enterprise of the St. Gotthard tunnel in 1883, ending in 1906 with the inauguration of the Simplon tunnel. The Milan congress is examined as well as the developments which, from then on, began increasingly to give physicians specialised in occupational diseases a higher profile in events of an international nature in the defence of workers' health but also in the interests of economic development.

[The Italian Society of Occupational Medicine and Industrial Hygiene: one hundred years of history]. / La Società Italiana di Medicina del Lavoro e di Igiene Industriale: cento anni di storia.

This research project, in conjunction with the SIMLII foundation's 80th anniversary, is aimed to reconstruct the historical chronology of the institutional life of the Society: the Directive bodies, the by-laws, the main steps of the scientific activity, especially the Congresses of Occupational Health. The research will also analyze the most important elements of historical context explaining Society's evolution: the relationships between SIMLII and political-institutional and legislative framework, social and economic changes, medical science's evolution and the university teaching and research, and finally the interactions with the international context. The research covers the years since the first national meeting of Occupation Health, in 1907, in which scientific activity was particularly intense, although the foundation was officially only in 1929. The investigation of the documentation after the 2nd World War is aimed at reconstructing the reborn of the international relations and the social, cultural and economic changes occurred between 1968 and 1978 and the deep impact on industrial relations and the enactment of the "Statuto dei lavoratori" in 1970 and the Health Reform in 1978.

Uncertainty, imprecision, and the precautionary principle in climate change assessment.

Statistical decision theory can provide useful support for climate change decisions made under conditions of uncertainty. However, the probability distributions used to calculate expected costs in decision theory are themselves subject to uncertainty, disagreement, or ambiguity in their specification. This imprecision can be described using sets of probability measures, from which upper and lower bounds on expectations can be calculated. However, many representations, or classes, of probability measures are possible. We describe six of the more useful classes and demonstrate how each may be used to represent climate change uncertainties. When expected costs are specified by bounds, rather than precise values, the conventional decision criterion of minimum expected cost is insufficient to reach a unique decision. Alternative criteria are required, and the criterion of minimum upper expected cost may be desirable because it is consistent with the precautionary principle. Using simple climate and economics models as an example, we determine the carbon dioxide emissions levels that have minimum upper expected cost for each of the selected classes. There can be wide differences in these emissions levels and their associated costs, emphasizing the need for care when selecting an appropriate class.

Phenylpropanoid glycosides in Italian Orobanche spp., sect. Orobanche.

We studied the occurrence of phenylpropanoid glycosides (PhG) in five species of the genus Orobanche L., collected in the Latium region of Italy. The presence of orobanchoside and verbascoside in all four species confirms that these PhGs are taxonomic markers of the genus. The results suggest that O. gracilis form. citrina could be a diverse entity.

Antibacterial activity of Hydrastis canadensis extract and its major isolated alkaloids.

The antibacterial activity of extract and isolated major alkaloids (berberine, beta-hydrastine, canadine and canadaline) of Hydrastis canadensis L. (Ranunculaceae) was evaluated against 6 strains of microorganism: Staphylococcus aureus (ATCC 25 993 and ATCC 6538P), Streptococcus sanguis (ATCC 10 556), Escherichia coli (ATCC 25 922), Pseudomonas aeruginosa (ATCC 27 853). Bactericidal activity was evaluated by contact test by measuring the "killing time" on a low density bacterial inoculum, and bacteriostatic activity in liquid medium by M.I.C. values. The results provide a rational basis for the traditional antibacterial use of Hydrastis canadensis.

Bis-iridoid glucosides from Abelia chinensis.

Seven bis-iridoid glucosides have been isolated from Abelia chinensis and were characterized by having a secoiridoid residue as unit A esterifying a C(10)-iridoid or a delta-lactone iridoid as unit B. Among these, compounds 1-3 are new and correspond to 7-O-acetyllaciniatoside IV, 7-O-acetyllaciniatoside V, and 7-O-acetylabelioside B, respectively. The structures of 1-3 were elucidated by spectral methods.

The utility and cost-effectiveness of D-dimer measurements in the diagnosis of deep vein thrombosis.

BACKGROUND AND OBJECTIVE: The potential utility of D-dimer measurements for the diagnosis of deep vein thrombosis became evident soon after the development of reliable commercial assays. The purpose of this review is to outline some critical aspects affecting cost-effectiveness of D-dimer measurements in the diagnosis of deep vein thrombosis (DVT). METHODS: The authors have been working in this field contributing original papers whose data have been used for this study. In addition, the material analyzed in this article includes papers published in the journals covered by the Science Citation Index and Medline. RESULTS: D-dimer levels are very sensitive to the process of fibrin formation/dissolution occurring with ongoing thrombosis. However, they may not be highly specific for venous thromboembolism as they are influenced by the presence of comorbid conditions potentially elevating plasma D-dimer (cancer, surgery, infectious diseases). In addition, commercially available ELISA assays, although quantitative and reproducible, cannot be used under emergency conditions because they are time-consuming and suited for batch-processing of plasma samples. Recently, new assays have been introduced which permit fast and quantitative D-dimer estimations in individual patients. We have evaluated the utility of two new rapid assays (LPIA D-dimer. Mitsubishi, and VIDAS D-DIMER, bio-Merieux) in combination with compression real-time-B-mode ultrasonography for the detection of deep vein thrombosis in asymptomatic patients following elective hip replacement and in patients with clinically suspected deep vein thrombosis. In both settings, we identified cut-off values with optimal sensitivity which allow exclusion of deep vein thrombosis in a considerable percentage of patients, with substantial sparing of economic resources. In fact, based on a cost-effectiveness analysis, a diagnostic algorithm combining D-dimers measurement and compression ultrasonography would result in cost-savings ranging from 5% to 55% in patients with high or low clinical pretest probability respectively. However, the specificity of D-dimer measurements for deep vein thrombosis was much higher in symptomatic than in asymptomatic patients. Choice of the cut-off value proved to be dependent on the method as well as on the patient populations studied. CONCLUSIONS: The cost-effectiveness of D-dimers measurement in the diagnosis of asymptomatic DVT remains questionable. Conversely, our data strongly support the utility of D-dimers determinations in the diagnosis of symptomatic DVT. In terms of sparing economic resources, the introduction in the clinical laboratory of the rapid quantitative assays would be highly convenient, because they avoid a source of bias in the interpretation of D-dimers results, are easy to perform and do not require dedicated personnel or instrumentation. Prospective management studies validating the utility of D-dimer measurement in the diagnosis of deep vein thrombosis are urgently needed.

Potential failure of the International Normalized Ratio (INR) System in the monitoring of oral anticoagulation in patients with lupus anticoagulants.

Patients with antiphospholipid antibody syndrome (APS) experience a higher rate of recurrence of thrombosis than the general population of patients with thrombotic disease. Based on a retrospective analysis, it has been suggested that patients with APS should be kept on prolonged anticoagulation aiming at international normalised ratio (INR) values > 3.0. To evaluate whether the requirement for more intense anticoagulation depends on the variable sensitivity of thromboplastin reagents to the influence of aPLA, we monitored oral anticoagulant treatment in 10 patients with persistent lupus anticoagulants (LA) and venous thromboembolic disease using two thromboplastin reagents: Pro-IL-Complex (Instrumentation Laboratory, combined) and Recombiplastin (Ortho, recombinant). Acenocoumarol dosage was always assigned based on INR values obtained with the combined thromboplastin using diluted (1:20) test plasma, aiming at an INR interval of 2.0 to 3.0. Single INR determinations with both reagents were obtained throughout the study period for 110 aPLA-free patients on stable oral anticoagulation. Using the manufacturer's instrument-certified international sensitivity index (ISI) values, INR obtained with the recombinant reagent were significantly higher than those obtained with the combined reagent in LA-positive patients, but they were lower in LA-negative patients. After correction for local ISI calibration in LA-negative patients, INR values of 3.1 and 4.6 with Recombiplastin corresponded, respectively, to INR values of 2.0 and 3.0 with Pro-IL-Complex. These results indicate the thromboplastin-dependency of INR values in patients with LA, thereby questioning the validity of the INR system for the monitoring of oral anticoagulant treatment in these patients.

Evaluation of a new rapid quantitative D-dimer assay in patients with clinically suspected deep vein thrombosis.

The sensitivity and specificity for deep vein thrombosis (DVT) of a new rapid, quantitative and precise (total imprecision < 10%) D-dimer assay suitable for individual measurements (VIDAS D-DIMER, bio-Mérieux, France) were evaluated in a consecutive series of 103 in- and out-patients submitted to serial compression ultrasonography (C-US) for the clinical suspicion of DVT (n = 66) or of DVT recurrence (n = 37) and symptoms lasting from 1 to 15 days. DVT was found in 22 patients at baseline testing and no patient with an initially negative C-US developed vein incompressibility at follow up. The time elapsed from the onset of symptoms was negatively associated with D-dimer levels both in patients with and in those without DVT. In the entire series of patients, the sensitivity of a positive D-dimer test ( > or = 1.0 microgram/ml) for the presence of DVT was 96% (21/22 patients, 95% confidence interval 75-100%) with a specificity of 75% (64-84%), a negative predictive value of 98% (90-100%), a positive predictive value of 51% (35-67%), and an overall accuracy of 80% (70-87%). A normal D-dimer value (0.22 microgram/ml) was observed in one patient with DVT and symptoms lasting from 15 days. The approach of withholding C-US testing in patients with symptoms lasting from less than 11 days and D-dimer levels below the cut-off value was compared to serial C-US testing alone in a cost-effectiveness analysis subdividing the 66 patients with a first episode according to their clinical pretest probability of DVT. Thrombosis was detected in 6.7% of the patients in the low probability group (n = 15), 16.7% of the patients in the moderate probability group (n = 24), 51.9% of the patients in the high probability group (n = 27) and 8.1% of patients with suspected DVT recurrence. Calculated cost-savings for each DVT diagnosed ranged from 5% in the high pretest probability group to 55% in the low pretest probability group and to 77% in patients with suspected DVT recurrence. The safety of avoiding C-US testing in symptomatic patients with a negative D-dimer test should be evaluated in clinical management studies.

An unusual C-skeleton type glucoside from Mentzelia incisa.

A new glucoside with unusual acyclic C13-skeleton has been isolated from Mentzelia incisa Urban et Gilg. The structure was assigned by spectroscopic means.

Synthesis, stereochemistry, and biological activity of the 1-(1-phenyl-2-methylcyclohexyl)piperidines and the 1-(1-phenyl-4-methylcyclohexyl)piperidines. Absolute configuration of the potent trans-(-)-1-(1-phenyl-2-methylcyclohexyl)piperidine.

The (-)- and (+)-isomers of the cis- and trans-Ph/Me 1-(1-phenyl-2-methylcyclohexyl)piperidines have been synthesized and the achiral cis- and trans-Ph/Me 1-(1-phenyl-4-methylcyclohexyl)piperidines were prepared, and their in vitro [displacement of [3H]TCP (1-[1-(2-thienylcyclohexyl)]piperidine) from the PCP (1-(1-phenylcyclohexyl)piperidine) binding site] and in vivo (rotarod assay) activities determined. The 1-(1-phenyl-2-methylcyclohexyl)piperidine isomers were resolved by classical crystallization procedures, through the diastereomeric salts obtained with d- and l-10-camphorsulfonic acid. The relative stereochemistry of the cis- and trans-Ph/Me 1-(1-phenyl-2-methylcyclohexyl)piperidines and the achiral cis- and trans-Ph/Me 1-(1-phenyl-4-methylcyclohexyl)piperidines was established by using 13C and 1H NMR. Both (-)-trans-1-(1-phenyl-2-methylcyclohexyl)piperidine ((-)-2) and (+)-trans-1-(1-phenyl-2-methylcyclohexyl)piperidine ((+)-2) were examined by single-crystal X-ray analysis, and the absolute configuration of (-)-2 was determined to be 1S,2R. The (-)-2 was found to be about five times more potent than PCP in vitro and twice as potent in vivo. It is the most potent of all of the simple methyl-substituted cyclohexyl PCP isomers and is among the most potent PCP-like compounds which have been synthesized. It was nine times more potent in vitro and four times more potent in vivo than (+)-2. The racemic cis-1-(1-phenyl-2-methylcyclohexyl)piperidine (3), and its enantiomers ((+)-3 and (-)-3), were essentially inactive in vitro and in vivo. The cis-Ph/Me 1-(1-phenyl-4-methylcyclohexyl)piperidine (18) was more potent than trans-Ph/Me 1-(1-phenyl-4-methylcyclohexyl)piperidine (17), but considerably less potent than (-)-2. The enantioselectivity observed at the PCP binding site for (-)-2 could indicate that this site can discriminate between enantiotopic edges of the achiral PCP (choosing the pro-1-S edge), as does the mu-opioid receptor in the prodine series of opioids. Benzimidoyl or benzoyl group replacement of the phenyl ring in the 1-(1-phenyl-2-methylcyclohexyl)piperidine series gave compounds which showed little in vitro and in vivo activity.

Iridoids in the Flora of Italy; Part 111. Kickxioside, A New Iridoid Glucoside from Kickxia spuria.

A new iridoid glucoside, 2, named kickxioside, was isolated from KICKXIA SPURIA. On the basis of spectral data, the structure of antirrhinoside esterified at position 6 by a menthiafolic acid was assigned to 2. The structure was also confirmed by alkaline hydrolysis of 2, which afforded antirrhinoside and menthiafolic acid.