Epidemiology of sepsis in Internal Medicine Units of Apulia: results of SEMINA (SEpsis Management in INternal medicine Apulia) study.

Background: The prevalence and mortality of sepsis in Internal Medicine Units (IMUs) is poorly understood as most of the data derive from studies conducted in Intensive Care Units. Aim of SEpsis Management in INternal medicine Apulia (SEMINA) study was to determine the prevalence of sepsis and the characteristics and outcomes of patients with Sepsis-3 criteria admitted in Apulia's Internal Medicine Units for over six months. Methods: The SEpsis Management in INternal medicine of Apulia study was a prospective, multicentre, observational study. Adult admissions to the 13 Apulia Region's Internal Medicine Units between November 15, 2018 and May 15, 2019 were screened for sepsis according to the Sepsis-3 criteria. Medical data were collected in electronic case report form. Results: Out of 7,885 adult patients of the Internal Medicine Units, 359 (4.55%) fulfilled the inclusion criteria, and 65 of them (18.1%) met the septic shock criteria. The patients enrolled were elderly, suffering from chronic poly-pathologies and from cognitive and functional impairment. The respiratory system was the most common site of infection and the most common pathogens isolated from blood cultures were Staphylococcus spp., E. coli, Klebsiella spp., Enterococcus spp. and Acinetobacter spp. The in-hospital fatality rate was 31.2% and was significantly higher for septic shock. Sequential Organ Failure Assessment score, dementia and infections from Acinetobacter spp. were independent risk factors for mortality. Conclusions: A high prevalence of sepsis and a high fatality rate were detected in Apulia Region's Internal Medicine Units. The high fatality rate observed in our study could be related to the underlying diseases and to the vulnerability of elderly patients admitted to our Internal Medicine Units.

The NATO project: nanoparticle-based countermeasures for microgravity-induced osteoporosis.

Recent advances in nanotechnology applied to medicine and regenerative medicine have an enormous and unexploited potential for future space and terrestrial medical applications. The Nanoparticles and Osteoporosis (NATO) project aimed to develop innovative countermeasures for secondary osteoporosis affecting astronauts after prolonged periods in space microgravity. Calcium- and Strontium-containing hydroxyapatite nanoparticles (nCa-HAP and nSr-HAP, respectively) were previously developed and chemically characterized. This study constitutes the first investigation of the effect of the exogenous addition of nCa-HAP and nSr-HAP on bone remodeling in gravity (1 g), Random Positioning Machine (RPM) and onboard International Space Station (ISS) using human bone marrow mesenchymal stem cells (hBMMSCs). In 1 g conditions, nSr-HAP accelerated and improved the commitment of cells to differentiate towards osteoblasts, as shown by the augmented alkaline phosphatase (ALP) activity and the up-regulation of the expression of bone marker genes, supporting the increased extracellular bone matrix deposition and mineralization. The nSr-HAP treatment exerted a protective effect on the microgravity-induced reduction of ALP activity in RPM samples, and a promoting effect on the deposition of hydroxyapatite crystals in either ISS or 1 g samples. The results indicate the exogenous addition of nSr-HAP could be potentially used to deliver Sr to bone tissue and promote its regeneration, as component of bone substitute synthetic materials and additive for pharmaceutical preparation or food supplementary for systemic distribution.

Sessile macrobenthos (Ochrophyta) drives seasonal change of meiofaunal community structure on temperate rocky reefs.

Unlike the soft bottom meiofauna, meiofauna associated to hard substrata is poorly studied, despite its ecological relevance. Since communities of hard substrata are usually characterized by species with different life cycles and strategies from those of soft bottom assemblages, information on hard substrata meiofauna is still needed. In this study, sessile macrobenthos and the associated meiofaunal assemblages of two sites of Portofino (NW Mediterranean) were investigated in two seasons at three different depths on both sub-vertical and inclined reefs. The study aimed to assess the abundance, diversity and composition of the meiofauna and the factors structuring its assemblages. Moreover, as meiofauna is known to be dependent upon the substrate characteristics, the study investigated whether the meiofaunal patterns could be related to the sessile macrobenthos structure and composition, and to which extent. Macroalgae dominated the sessile macrobenthic assemblages, while Nematoda and Copepoda were the main meiofaunal groups. Meiofaunal higher-taxa richness and diversity resulted very high, due to the large number of different microhabitats offered by macroalgae. Macrobenthic assemblages were dominated by Rodophyta and Ochrophyta in summer, the latter dramatically collapsing in winter. The meiofaunal abundance and composition changed significantly with the season, consistently with the sessile macrobenthic assemblages, and resulted strongly correlated with Ochrophyta. Shaping the meiofaunal assemblages, macroalgae appeared to act as ecosystem engineer for the meiofauna.

Do the morphological and functional traits of free-living marine nematodes mirror taxonomical diversity?

The taxonomical structure and diversity of nematode assemblages are the main attributes analyzed in ecology, but nematode adaptations to their habitats are still understudied. Accordingly, a survey on some known and other newly proposed morpho-functional traits was carried out in order to: determine if the morpho-functional diversity of nematodes mirrors their taxonomical diversity; and assess potential nematode adaptations to sediment type and hydrodynamic stress. Morpho-functional traits were investigated both singularly and together and showed significant differences related to these environmental factors. The greatest taxonomical and morpho-functional diversity was found in medium-coarse sand (M-CS) and at an intermedium energy level (IEL). The M-CS and IEL were probably richer in micro-habitats and subject to a low selective pressure, hosting nematodes with a wide range of adaptations. The mirroring of morpho-functional diversity with taxonomical diversity is crucial for the future growth of the use of nematodes in biomonitoring. This is because the study of their morpho-functional traits could reduce the level of work involved and the costs of any analyses.

Lamellipodin promotes invasive 3D cancer cell migration via regulated interactions with Ena/VASP and SCAR/WAVE.

Cancer invasion is a hallmark of metastasis. The mesenchymal mode of cancer cell invasion is mediated by elongated membrane protrusions driven by the assembly of branched F-actin networks. How deregulation of actin regulators promotes cancer cell invasion is still enigmatic. We report that increased expression and membrane localization of the actin regulator Lamellipodin correlate with reduced metastasis-free survival and poor prognosis in breast cancer patients. In agreement, we find that Lamellipodin depletion reduced lung metastasis in an orthotopic mouse breast cancer model. Invasive 3D cancer cell migration as well as invadopodia formation and matrix degradation was impaired upon Lamellipodin depletion. Mechanistically, we show that Lamellipodin promotes invasive 3D cancer cell migration via both actin-elongating Ena/VASP proteins and the Scar/WAVE complex, which stimulates actin branching. In contrast, Lamellipodin interaction with Scar/WAVE but not with Ena/VASP is required for random 2D cell migration. We identified a phosphorylation-dependent mechanism that regulates selective recruitment of these effectors to Lamellipodin: Abl-mediated Lamellipodin phosphorylation promotes its association with both Scar/WAVE and Ena/VASP, whereas Src-dependent phosphorylation enhances binding to Scar/WAVE but not to Ena/VASP. Through these selective, regulated interactions Lamellipodin mediates directional sensing of epidermal growth factor (EGF) gradients and invasive 3D migration of breast cancer cells. Our findings imply that increased Lamellipodin levels enhance Ena/VASP and Scar/WAVE activities at the plasma membrane to promote 3D invasion and metastasis.

Meiobenthos and free-living nematodes as tools for biomonitoring environments affected by riverine impact.

The effects of the human impact on the coastal environments and relative biota can be different and even greater than those derived by natural fluctuations. The major disturbance causes in the coastal systems are rivers that may be important sources of nutrients and pollutants, particularly in a semi-closed basin such as the Adriatic Sea. In this context, we investigated the distribution of both meiobenthic and nematode assemblages in the Central Adriatic Sea to evaluate whether and how they are influenced by riverine discharges and which faunal descriptors are the most effective in detecting this type of stress. On the basis of our results, the disturbance effects in the studied area might be caused by both local streams and Po plume, and even if the latter might be considered of lesser extent, it is worthy to note its real impact at a short distance from the coastline. Meiobenthic assemblage structure appears as a good tool for detecting short-term responses of the benthic domain, whereas nematode assemblages seem more useful for defining long-term responses. Accordingly, the former highlighted from poor to sufficient ecological quality status (EQS) of this area, whereas the latter from moderate to bad EQS. Life strategy traits prove to be the most informative faunal descriptor due to their high correspondence with the environmental variables and particularly with this type of disturbance.

Chikungunya infection in a human immunodeficiency virus-infected kidney transplant recipient returning to Italy from the Dominican Republic.

Since December 2013, chikungunya virus (CHIKV) spread in many countries of the Western Hemisphere, and during the last year some cases of infected European travelers, coming back from the Caribbean, have been reported. The risk of acquiring severe travel-related illness is higher in immunocompromised subjects, such as patients with human immunodeficiency virus (HIV) infection or solid organ transplant recipients. We reported the first case, to our knowledge, of CHIKV infection in an HIV-infected kidney transplant recipient.

Left ventricular remodelling in asymptomatic HIV infection on chronic HAART: comparison between hypertensive and normotensive subjects with and without HIV infection.

The high cardiovascular risk of HIV infected (HIV+) patients is still partly unexplained. We aimed to evaluate if HIV infection and highly active antiretroviral therapy (HAART) are linked per se to left ventricular (LV) remodelling, independently of blood pressure (BP) values. We enrolled 4 groups of patients matched by gender, age, body mass index and smoking habit: 30 HIV+ hypertensives, 30 HIV+ normotensives, 30 not-infected (HIV-) hypertensives and 30 HIV- normotensives. HIV+ patients were on chronic HAART. Hypertension was newly diagnosed (≤6 months) and never treated. Each patient underwent blood tests, 24-h BP monitoring and LV echocardiogram. The 4 groups had similar fasting glucose and cholesterol; triglycerides, HOMA index and prevalence of metabolic syndrome were higher in the HIV+ groups. Despite similar 24-h BP values, HIV+ hypertensives had greater LV mass and higher prevalence of preclinical diastolic dysfunction than HIV- hypertensives. Compared to HIV- normotensives, HIV+ normotensives had similar 24-h BP values, but greater LV mass and lower LV diastolic indices, similar to HIV- hypertensives, whose 24-h BP values were higher. Asymptomatic HIV infection and chronic HAART are associated with myocardial hypertrophy and preclinical diastolic dysfunction, independently of BP values.

Pulmonary tuberculosis in an HIV- and hepatitis C virus-coinfected kidney-pancreas transplant recipient: a case report.

Tuberculosis (TB) is a serious infection in immunocompromised patients, such as solid organ transplant recipients and HIV-infected patients. The diagnosis and treatment in this population present several challenges because of the aspecific clinical manifestations, the difficulty in diagnosis, and the choice of the most appropriate therapeutic regimen. Therapeutic challenges arise from drug-related toxicities, interactions between immunosuppressive, antiretroviral, and antituberculous drugs. We present a case of primary TB infection that occurred 3 years after transplantation in a HIV-and hepatitis C virus-coinfected kidney-pancreas recipient. The infection was successfully treated with no hepatotoxicity or rejection with a non-rifampin-containing regimen.

Polymeric adsorbent for removing toxic proteins from blood of patients with kidney failure.

A hypercrosslinked styrenic polymer with an enhanced proportion of mesopores in the range 2-20 nm has been developed. The principle of the synthesis consists of the suspension polymerization of divinylbenzene (or copolymerization of styrene with divinylbenzene) in the presence of a porogen that is a theta-solvent for polystyrene. On the scale of thermodynamic affinity, theta-solvents occupy a border position between good solvents and precipitating media for the growing polymer chains. In this case, microphase separation takes place during the final stages of the polymerization process. The polymer was shown to adsorb 93-98% of beta2-microglobulin from the blood or plasma of patients with chronic kidney failure. At the same time, large essential proteins, like albumin, are not removed to a significant extent, obviously, due to the size-exclusion effect and the difference in the hydrophobicity of the proteins. By replacing surface exposed pendant vinyl groups of the polymer with hydrophilic functional groups, the material was made hemocompatible, according to the standard battery of biocompatibility tests required by ISO 10993 guidelines. No adverse effects such as fever or hypotension were noted in dogs in direct hemoperfusion experiments with the polymer.

Novelty in phylogeny of gastrotricha: evidence from 18S rRNA gene.

Gastrotricha form a phylum which is crucial for defining the origin of pseudocoelomates, in that they share a number of characters with Rotifera and Nematoda but also with acoelomates, and even the evolutionary relationships within the phylum are anything but defined. For this reason the first extensive molecular data on Gastrotricha from the 18S rRNA sequences of both orders have been obtained and analyzed. Sequence analyses show that the phylum Gastrotricha is strictly monophyletic along an evolutionary line quite distinct from that of both Rotifera and Nematoda. A new view of the evolutionary history of the phylum Gastrotricha is put forward, in which Chaetonotida, and not Macrodasyida, are the most primitive forms of the group, contrary to the commonly held view. A polyphyletic origin of aschelminthes is supported, and the misleading term pseudocoelomates should be discarded.

Isolation of progesterone-dependent complementary deoxyribonucleic acid fragments from rhesus monkey endometrium by sequential subtractive hybridization and polymerase chain reaction amplification.

The steroid sex hormone progesterone (P) induces the expression of a variety of genes through a signal transduction pathway mediated by the P receptor, a DNA-binding regulator of transcription. To identify genes and gene networks that are P dependent in the rhesus endometrium, we used a powerful technique employing subtractive hybridization coupled with polymerase chain reaction (PCR). Poly(A)+ RNA was isolated from both P-dominant (days 21-23 of artificial menstrual cycles) and estrogen (E)-dominant (days 9-13) endometrium. The two classes of RNA were converted to cDNA, ligated to EcoRI adaptors, and amplified by PCR using an adaptor-complimentary primer. E-dominant cDNA was labeled with biotin, hybridized in excess to P-dominant cDNA (PcDNA), and complexed with streptavidin. Labeled cross-hybrid sequences common to both populations were subtracted by phenol-chloroform extraction. The remaining cDNA fragments were amplified by PCR. After four rounds of hybridization/amplification, the subtracted PcDNA was analyzed for P-dependent sequences by semiquantitive PCR. Initial analysis revealed that housekeeping genes were undetectable in subtracted cDNA, but a previously characterized P-dependent gene was retained. Three of five clones sequenced at random from the subtracted library exhibited P-inducibility/dependency by PCR analysis of E and PcDNA. One of these, an 835-basepair fragment designated H5, may represent a novel P-dependent gene, as no comparable homology could be found with existing sequences in GenBank and Swissprot databases. We estimate that the procedure described here resulted in highly significant enrichment of up-regulated cDNA fragments from P-dominant tissue.

A double immunofluorescent method for simultaneous analysis of progesterone-dependent changes in proliferation and the oestrogen receptor in endometrium of rhesus monkeys.

A double immunofluorescent technique that permitted the nuclear localization of both the oestrogen receptor and the Ki-67 antigen (marker of cell proliferation) within the same tissue section was developed and used to determine the relationship between the oestrogen receptor and proliferation within the major zones of the primate endometrium. Endometrial tissue was obtained from ovariectomized rhesus monkeys in which the hormonal pattern of oestradiol and progesterone was simulated with Silastic implants containing each hormone. The oestrogen receptor was detected using the H222 rat monoclonal antibody and Texas Red conjugated streptavidin. Immunofluorescent staining of a mouse monoclonal antibody to the Ki-67 antigen was detected by an antibody to mouse IgG conjugated with fluorescein isothiocyanate. Primary antibodies were co-incubated with tissue sections followed by sequential detection of the oestrogen receptor and Ki-67. A dual wavelength filter was used to monitor simultaneously both immunofluorescent patterns. Application of this technique to study regulation of endometrial proliferation and oestrogen receptor content by progesterone showed that the endometrium exhibited two different responses to progesterone: luminal and glandular epithelia and stromal cells in the functionalis and zone III of the basalis showed coincident decreases of oestrogen receptor and proliferation, whereas the oestrogen receptor in glandular epithelia of zone IV (basalis) was not downregulated and there was an increase in proliferation.

Progesterone regulation of endometrial estrogen receptor and cell proliferation during the late proliferative and secretory phase in artificial menstrual cycles in the rhesus monkey.

Progesterone (P) down-regulation of uterine estradiol (E) receptor (ER) appears to be a general mechanism by which P modulates E action in the uterus. Our present studies focus on the regulation of ER by P during the changeover from E to P dominance during artificial menstrual cycles in the rhesus monkey. Because of differential cell-type response and the cellular zonation of the primate uterus, we used immunohistochemical analysis in addition to biochemical assays to study the regulation of ER by P. Ki-67 immunoreactivity was used as an index of endometrial proliferation. We performed our analyses on Days 13 (peak of E), 14 (declining E and rising P), 17 (basal E and rising P), and 21 (basal E and peak P). ER immunoreactivity was present throughout the endometrium in luminal and glandular epithelia and stromal fibroblasts on Day 13. As E was withdrawn and P rose on Day 14 there were few distinct changes in ER staining in stromal and epithelial cells. On Day 17, immunoreactive staining showed a distinct reduction for stromal cells in all zones. Although luminal epithelial cells showed a decrease in immunoreactivity on Day 17, zones II, III, and IV retained positive staining for ER in glandular epithelia. ER staining in stromal cells on Day 21 was similar to the pattern observed on Day 17, whereas epithelial cells in zones I, II, and III showed a reduction in staining. Glandular epithelia in zone IV maintained strong positive staining for ER on Day 21.(ABSTRACT TRUNCATED AT 250 WORDS)