Circadian Rhythms and Astrocytes: The Good, the Bad, and the Ugly.

This review explores the interface between circadian timekeeping and the regulation of brain function by astrocytes. Although astrocytes regulate neuronal activity across many time domains, their cell-autonomous circadian clocks exert a particular role in controlling longer-term oscillations of brain function: the maintenance of sleep states and the circadian ordering of sleep and wakefulness. This is most evident in the central circadian pacemaker, the suprachiasmatic nucleus, where the molecular clock of astrocytes suffices to drive daily cycles of neuronal activity and behavior. In Alzheimer's disease, sleep impairments accompany cognitive decline. In mouse models of the disease, circadian disturbances accelerate astroglial activation and other brain pathologies, suggesting that daily functions in astrocytes protect neuronal homeostasis. In brain cancer, treatment in the morning has been associated with prolonged survival, and gliomas have daily rhythms in gene expression and drug sensitivity. Thus, circadian time is fast becoming critical to elucidating reciprocal astrocytic-neuronal interactions in health and disease.

Circadian regulation of MGMT expression and promoter methylation underlies daily rhythms in TMZ sensitivity in glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common primary brain tumor in adults. Despite extensive research and clinical trials, median survival post-treatment remains at 15 months. Thus, all opportunities to optimize current treatments and improve patient outcomes should be considered. A recent retrospective clinical study found that taking TMZ in the morning compared to the evening was associated with a 6-month increase in median survival in patients with MGMT-methylated GBM. Here, we hypothesized that TMZ efficacy depends on time-of-day and O6-Methylguanine-DNA Methyltransferase (MGMT) activity in murine and human models of GBM. METHODS AND RESULTS: In vitro recordings using real-time bioluminescence reporters revealed that GBM cells have intrinsic circadian rhythms in the expression of the core circadian clock genes Bmal1 and Per2, as well as in the DNA repair enzyme, MGMT. Independent measures of MGMT transcript levels and promoter methylation also showed daily rhythms intrinsic to GBM cells. These cells were more susceptible to TMZ when delivered at the daily peak of Bmal1 transcription. We found that in vivo morning administration of TMZ also decreased tumor size and increased body weight compared to evening drug delivery in mice bearing GBM xenografts. Finally, inhibition of MGMT activity with O6-Benzylguanine abrogated the daily rhythm in sensitivity to TMZ in vitro by increasing sensitivity at both the peak and trough of Bmal1 expression. CONCLUSION: We conclude that chemotherapy with TMZ can be dramatically enhanced by delivering at the daily maximum of tumor Bmal1 expression and minimum of MGMT activity and that scoring MGMT methylation status requires controlling for time of day of biopsy.

Comprehensive Associations between Acidosis and the Skeleton in Patients with Kidney Disease.

SIGNIFICANCE STATEMENT: Renal osteodystrophy (ROD) contributes substantially to morbidity in CKD, including increased fracture risk. Metabolic acidosis (MA) contributes to the development of ROD, but an up-to-date skeletal phenotype in CKD-associated acidosis has not been described. We comprehensively studied associations between acidosis and bone in patients with CKD using advanced methods to image the skeleton and analyze bone-tissue, along with biochemical testing. Cross-sectionally, acidosis was associated with higher markers of bone remodeling and female-specific impairments in cortical and trabecular bone quality. Prospectively, acidosis was associated with cortical expansion and trabecular microarchitectural deterioration. At the bone-tissue level, acidosis was associated with deficits in bone mineral content. Future work investigating acidosis correction on bone quality is warranted. BACKGROUND: Renal osteodystrophy is a state of impaired bone quality and strength. Metabolic acidosis (MA) is associated with alterations in bone quality including remodeling, microarchitecture, and mineralization. No studies in patients with CKD have provided a comprehensive multimodal skeletal phenotype of MA. We aim to describe the structure and makeup of bone in patients with MA in the setting of CKD using biochemistry, noninvasive imaging, and histomorphometry. METHODS: The retrospective cross-sectional analyses included 180 patients with CKD. MA was defined as bicarbonate ≤22 mEq/L. We evaluated circulating bone turnover markers and skeletal imaging with dual energy x-ray absorptiometry and high-resolution peripheral computed tomography. A subset of 54 participants had follow-up. We assessed associations between baseline and change in bicarbonate with change in bone outcomes. Histomorphometry, microCT, and quantitative backscatter electron microscopy assessed bone biopsy outcomes in 22 participants. RESULTS: The mean age was 68±10 years, 54% of participants were male, and 55% were White. At baseline, acidotic subjects had higher markers of bone turnover, lower areal bone mineral density at the radius by dual energy x-ray absorptiometry, and lower cortical and trabecular volumetric bone mineral density and impaired trabecular microarchitecture. Over time, acidosis was associated with opposing cortical and trabecular effects: cortical expansion but trabecular deterioration. Bone-tissue analyses showed reduced tissue mineral density with increased heterogeneity of calcium distribution in acidotic participants. CONCLUSIONS: MA is associated with multiple impairments in bone quality. Future work should examine whether correction of acidosis improves bone quality and strength in patients with CKD.

A New Wound-Healing Tool Based on Glycyrrhiza glabra Extract-Loaded Ufasomes on Spanish Broom Dressings.

The development of innovative products for restoring skin integrity and promoting wound healing is still a challenge. The aim of this work was to evaluate an innovative Spanish broom wound dressing impregnated with Glycyrrhiza glabra extract-loaded ufasomes to improve wound healing. Ufasomes were characterized in terms of size, polydispersity index, entrapment efficiency, zeta potential, and stability. In addition, in vitro release studies and biocompatibility, biosafety, and scratch tests on WS1 fibroblasts were performed. The loaded ufasomes showed a nanometric size (<250 nm), good size distribution (lower than 0.3), and appropriate encapsulation efficiency (~67%). Moreover, the lipid vesicles showed good stability during the storage period and allowed for a slow release of glycyrrhizin, the main bioactive compound of the extract. Biological studies revealed that loaded vesicles are not cytotoxic, are hemocompatible, and lead to the complete closure of the scratch after about 33 h. To conclude, the results suggest that the developed dressings can be efficiently used to promote the healing process.

Probiotic bacilli incorporation in foods: is really so easy?

Foods containing probiotic bacilli spores are becoming more and more popular because of their resistance to acidic pH, low water activity, and, most importantly, heat processes. Even though spores may engage in some functions, such as immunomodulation, the majority of the beneficial characteristics are unique to vegetative cells. As matter of fact, the development of foods fortified with spores ought to even ensure the germination of the spores along the gastrointestinal tract. In this perspective, vegetative cells derived from spore germination were separately counted on a minimal medium because the traditional approach is based on the use of complex media that allows the spores to germinate independently by stimuli arising from processing or digestion. In more detail, three Bacillus spp. cultures with claimed probiotic properties were added to two entirely unrelated foods (pasta and croissants), and tolerance, as well as germination, was monitored before and after exposure to simulated GIT, as well as at the beginning and end of the products shelf life. For the first time, potential probiotic bacilli were included in a frozen ready-to-bake product. Germination appears to be prevented in this instance, and the impact of baking, matrix and cold storage on spores was examined independently. All of the parameters appeared to contribute, although further research is needed due to the unpredictable behavior exhibited by spores during freezing.

Inter-Institutional Collaboration Between Quaternary and Tertiary Hospitals: Cardiac Surgery Impact.

BACKGROUND: An inter-institutional collaboration between a quaternary hospital (QH) with a high volume of cardiac surgery and a community-based, tertiary hospital (TH) with a newly established cardiac surgery program was established. METHODS: We retrospectively reviewed data of patients admitted to the TH between September 2015 and June 2017 for cardiac surgery. The decision to transfer a patient to the QH was based on a Society of Thoracic Surgeon-Predicted Risk of Mortality (STS-PROM) score of ≥ 3%, the potential need for hemodialysis, and other risk factors. The same team of surgeons performed operations at both hospitals. We analyzed the perioperative outcomes of the patients and the referral pattern. RESULTS: A total of 116 patients met eligibility criteria; 105 underwent surgery at the TH, while 11 were transferred to the QH. Among the 11 patients transferred to the QH, eight had a score of  3% (median = 8.2 [IQR 5.7-25.0]). The patients transferred to the QH prior to surgery had a significantly higher STS-PROM score (P = ≤ .001). Overall, the mortality of patients who underwent surgery at the TH was 0.9% (1/105); while surgeries at the QH had a mortality rate of 0% (0/11). CONCLUSION: The collaborative effort between high-volume cardiac surgery programs and emerging community-based hospitals showed acceptable outcomes in perioperative cardiac surgical mortality. Elevated STS-PROM scores (>3%), previous sternotomy and anticipation of coagulopathy, and low left ventricular ejection fraction or dilated ventricles are factors that influenced the need to transfer from a TH to QH.

Effect of Salt Addition and Fermentation Time on Phenolics, Microbial Dynamics, Volatile Organic Compounds, and Sensory Properties of the PDO Table Olives of Gaeta (Italy).

'Oliva di Gaeta' is almost certainly the most important and well-known PDO denomination for table olives in Italy. Their production is based on a specific two-stage trade preparation called the 'Itrana' method. In this work, we investigated how variations in the duration of the initial water fermentation (i.e., 15 and 30 days) and the salt concentration (i.e., 6% and 8% NaCl) influence the chemical features, microbial dynamics, polyphenols, volatile organic compounds, and sensory features of 'Oliva di Gaeta'. The time of the addition of salt did not affect the final concentration in the brine, but a longer initial water fermentation (before salt addition) led to lower pH values. The bacterial count constantly increased until the salt addition (i.e., either 15 or 30 days), while the yeast population peaked on day 30. Generally, the two different salt concentrations did not affect the count of microorganisms at the end of fermentation, with the only exception being a higher lactic acid bacteria count for the treatment with 6% salt added at 30 days. At commercial maturity, the crucial bitter tastant oleuropein was not completely removed from the drupes, and differences in salt concentration and the length of the first-stage water fermentation did not influence its content at the end of olive curing. Richer volatile profiles of olives were detected with higher-salt treatments, while the combination of low salt and early saline treatment provided a more distinct profile. Longer initial water fermentation caused a small increase in some phenolic compounds (e.g., iso-verbascoside, verbascoside, and hydroxytyrosol-glucoside). A panel test indicated that salt application at 30 days resulted in a more "Sour" and "Bitter" taste, irrespective of the salt concentration. The low salt concentration coupled with the late saline treatment resulted in more "Fruity" notes, probably due to the higher production of esters by lactobacilli. The slightly bitter perception of the olives was consistent with the partial removal of oleuropein. Our work revealed the characteristics of the 'Itrana' method and that the variation in salt concentration and its time of application changes parameters ranging from the microbial dynamics to the sensory profile. Specifically, our data indicate that 6% NaCl coupled with a longer initial water fermentation is the most different condition: it is less effective in blocking microbial growth but, at the same time, is more potent in altering the nutritional (e.g., polyphenols) and sensorial qualities (e.g., bitterness and fruitiness) of 'Oliva di Gaeta'.

Polyphenol Profiling of Chestnut Pericarp, Integument and Curing Water Extracts to Qualify These Food By-Products as a Source of Antioxidants.

Plant polyphenols have beneficial antioxidant effects on human health; practices aimed at preserving their content in foods and/or reusing food by-products are encouraged. The impact of the traditional practice of the water curing procedure of chestnuts, which prevents insect/mould damage during storage, was studied to assess the release of polyphenols from the fruit. Metabolites extracted from pericarp and integument tissues or released in the medium from the water curing process were analyzed by matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and electrospray-quadrupole-time of flight-mass spectrometry (ESI-qTOF-MS). This identified: (i) condensed and hydrolyzable tannins made of (epi)catechin (procyanidins) and acid ellagic units in pericarp tissues; (ii) polyphenols made of gallocatechin and catechin units condensed with gallate (prodelphinidins) in integument counterparts; (iii) metabolites resembling those reported above in the wastewater from the chestnut curing process. Comparative experiments were also performed on aqueous media recovered from fruits treated with processes involving: (i) tap water; (ii) tap water containing an antifungal Lb. pentosus strain; (iii) wastewater from a previous curing treatment. These analyses indicated that the former treatment determines a 6-7-fold higher release of polyphenols in the curing water with respect to the other ones. This event has a negative impact on the luster of treated fruits but qualifies the corresponding wastes as a source of antioxidants. Such a phenomenon does not occur in wastewater from the other curing processes, where the release of polyphenols was reduced, thus preserving the chestnut's appearance. Polyphenol profiling measurements demonstrated that bacterial presence in water hampered the release of pericarp metabolites. This study provides a rationale to traditional processing practices on fruit appearance and qualifies the corresponding wastes as a source of bioactive compounds for other nutraceutical applications.

Production of probiotic bovine salami using Lactobacillus plantarum 299v as adjunct.

BACKGROUND: Five probiotic lactobacilli were tested, alone or in combination with two commercial starters, to select the most suitable strain for a probiotic bovine salami production. Lactobacillus plantarum 299v was used with both starters, to make salami according to a traditional recipe. Salami obtained by using just the starters and by spontaneous fermentation, served as control. Microbial dynamics, as well as the main physico-chemical parameters, were monitored throughout ripening. The survival of probiotic 299v was confirmed by strains' tracking by means of RAPD-PCR coupled to a culture-independent approach PCR-DGGE-based. RESULTS: The results showed a remarkable viability of the probiotic strain even after 60 days of storage. Experimental salami exhibited the same level of sensory acceptance of control salami, were hygienically safe, and characterised by pH, weight loss and microbiological loads within the ranges conventionally advocated for optimal fermented sausages. CONCLUSION: Outcomes indicate the workable possibility of using second-quality beef cuts for probiotic salami production. © 2017 Society of Chemical Industry.

Persistence of bacterial indicators and zoonotic pathogens in contaminated cattle wastes.

BACKGROUND: Manure can provide a favourable environment for pathogens' survival. De-contamination may be conducted by extended storage, until field conditions are suitable for application to land as source of agricultural nutrients. RESULTS: The hygienic evaluation of manure and slurry coming from a plant that collects cattle livestock wastes from a big slaughterhouse was carried out. Samples were even collected from spillages in the area around the plant. Microbial analyses highlighted the massive presence of faecal indicators in all samples: mean counts of Escherichia coli and enterococci were always above EU limits for marketable processed manure products. Cultures referable to the genus Brucella spp. were recorded in two samples of fresh manure but not in the aged ones. Conventional isolation techniques failed to detect members of the Mycobacterium genus, while by means of IS900 and F57 PCR real-time system on DNA directly extracted from environmental samples, the pathogen was detected in all cases. CONCLUSIONS: Thoughtful design of manure storage infrastructure is critical to prevent spills and over-topping of an open structure. The documented overload situation seems to lay the basis for an ongoing environmental contamination by enteric organisms and opportunistic pathogens circuit faecal-oral route. Moreover, the type of wastes analysed during this study, namely a mixture of fresh cattle manure, bedding and rumen content, needs a longer storage period or, alternatively, of specific chemical, biological or thermal treatments for stabilization.

Effect of yeast strain and some nutritional factors on tannin composition and potential astringency of model wines.

Nine Saccharomyces cerevisiae cultures, isolated from different sources, were tested for their ability to reduce tannins reactive towards salivary proteins, and potentially responsible for wine astringency. Strains were preliminary genetically characterized and evaluated for physiological features of technological interest. Laboratory-scale fermentations were performed in three synthetic media: CT) containing enological grape tannin; CTP) CT supplemented with organic nitrogen sources; CTPV) CTP supplemented with vitamins. Adsorption of total tannins, tannins reactive towards salivary proteins, yellow pigments, phenolics having antioxidant activity, and total phenols, characterizing the enological tannin, was determined by spectrophotometric methods after fermentation. The presence of vitamins and peptones in musts greatly influenced the adsorption of tannins reactive towards salivary proteins (4.24 g/L gallic acid equivalent), thus promoting the reduction of the potential astringency of model wines. With reference to the different phenolic classes, yeast strains showed different adsorption abilities. From a technological point of view, the yeast choice proved to be crucial in determining changes in gustative and mouthfeel profile of red wines and may assist winemakers to modulate colour and astringency of wine.

Variability in chemical and microbiological profiles of long-ripened Caciocavallo cheeses.

Five protected designation of origin (PDO) Caciocavallo Silano and 6 non-PDO Caciocavallo cheeses, ripened for 6mo and collected in the 5 Italian regions of the PDO area (Apulia, Basilicata, Calabria, Campania, and Molise, Italy), were studied to assess their physico-chemical (pH, acidity, moisture, fat, ash, protein, and free amino acid composition) and microbiological profiles. Analyses evidenced a certain fluctuation of previous parameters among samples regardless of the kind of cheese evaluated (PDO and non-PDO). The PCR-denaturing gradient gel electrophoresis analysis performed on the DNA directly extracted from cheeses gave different results, but a low number of bands was always observed. Only one band, corresponding to the species Streptococcus thermophilus, was detectable in 1 PDO and in 2 non-PDO cheese samples, whose free amino acid content was the lowest. Analyses were repeated on experimental Caciocavallo cheeses. Specifically, 2 productions were made, one mimicking the industrial technology (pasteurized milk and selected starter culture) and one the artisanal technology (raw milk and natural whey starter). Results obtained on experimental cheeses at 6mo of ripening showed that industrial samples had lower amounts of total free amino acids then the artisanal ones (1,188.2 vs. 7,523.67mg/100 g of dry matter). Moreover, the PCR-denaturing gradient gel electrophoresis analysis evidenced the sole presence of S. thermophilus in the case of the industrial technology. These data sustain the hypothesis that, out of 11 cheeses analyzed previously, 1 PDO Caciocavallo Silano and 2 non-PDO Caciocavallo cheeses were obtained with the industrial technology. These results could be of help in the discrimination of PDO products, taking into account that the PDO production regulation does not allow the milk pasteurization, nor the use of selected starters.

Impact of different spray-drying conditions on the viability of wine Saccharomyces cerevisiae strains.

Spray-drying (SD) is widely considered a suitable method to preserve microorganisms, but data regarding yeasts are still scanty. In this study, the effect of growing media, process variables and carriers over viability of a wild wine Saccharomyces (S.) cerevisiae LM52 was evaluated. For biomass production, the strain was grown (batch and fed-batch fermentation) in a synthetic, as well as in a beet sugar molasses based-medium. Drying of cells resuspended in several combinations of soluble starch and maltose was performed at different inlet and outlet temperatures. Under the best conditions-suspension in soluble starch plus maltose couplet to inlet and outlet temperatures of 110 and 55 °C, respectively-the loss of viability of S. cerevisiae LM52 was 0.8 ± 0.1 and 0.5 ± 0.2 Log c.f.u. g(-1) for synthetic and molasses-based medium, respectively. Similar results were obtained when S. cerevisiae strains Zymoflore F15 and EC1118, isolated from commercial active dry yeast (ADY), were tested. Moreover, powders retained a high vitality and showed good fermentation performances up to 6 month of storage, at both 4 and -20 °C. Finally, fermentation performances of different kinds of dried formulates (SD and ADY) compared with fresh cultures did not show significant differences. The procedure proposed allowed a small-scale production of yeast in continuous operation with relatively simple equipment, and may thus represent a rapid response-on-demand for the production of autochthonous yeasts for local wine-making.

Characterisation, in vitro digestibility and expected glycemic index of commercial starches as uncooked ingredients.

In this study native starches as ingredients (corn, rice, wheat, tapioca and potato) were characterized for microstructure, physicochemical, functional and thermal properties, in vitro digestibility and glycemic index. There was a significant variation in the granule shape and size distribution of the starches. Particle size monomodal (corn, tapioca, potato) and bimodal (rice, wheat) distribution was observed amongst the starches. The potato starch showed the biggest size granules while the rice showed the smallest. The examined properties and nutritional characteristics of starches were significantly different. Thermal properties were studied using Differential Scanning Calorimeter (DSC). DSC results showed that the transition temperatures (58.8-78.7 °C) and enthalpies of gelatinization (2.3-8.2 J/g) of the starches appeared to be greatly influenced by microstructure and chemical composition (e.g. resistant starch). Nutritional properties such as slowly digestible starch and expected glycemic index values followed the order: rice > wheat > tapioca > corn > potato. In particular, the highest resistant starch was recorded for potato starch.

The effects of probiotics and prebiotics on the fatty acid profile and conjugated linoleic acid content of fermented cow milk.

The ability of probiotic bacteria (Lactobacillus acidophilus La5 and Bifidobacterium animalis Bb12), to produce conjugated linoleic acid (CLA) in association with Streptococcus thermophilus and Lb. bulgaricus during milk fermentation has been evaluated in this study. Pasteurized cow milk and infant formula were used. Infant formula was selected for its high linoleic acid content, for being a source of CLA and for its prebiotic compounds, e.g. galacto-oligosaccharides. The microorganisms were not able to increase the CLA content of the fermented products under the given experimental conditions. No statistically significant differences (p > 0.05) occurred between the CLA content in milk and the fermented samples. The CLA contents of 10 commercial fermented milk products were determined. The highest CLA content was observed in fermented milk containing only Str. thermophilus and Lb. bulgaricus.

Pulmonary hypertension in potential heart transplant recipients: current treatment strategies.

PURPOSE OF REVIEW: Pulmonary hypertension associated with left heart disease is the most commonly encountered form of pulmonary hypertension and is associated with a poor prognosis. As the global burden of heart failure grows, this associated disease can be a major impediment to those patients undergoing cardiac transplantation, given its association with post-transplant right ventricular failure. Unfortunately, the pathophysiology of pulmonary hypertension secondary to left heart failure remains poorly understood, thereby rendering targeted treatment strategies largely undefined. In this review, we provide a review of the currently available literature in this unique patient population. RECENT FINDINGS: The current focus on better defining the underlying pathophysiology and standardizing diagnostic and therapeutic approaches to pulmonary hypertension associated with left heart disease need to be interpreted and made applicable in the context of clinical practice. Given the relative paucity of successful, targeted pharmacological options, there is an increasing evidence that device-based therapies, used in conjuncture with medical therapy, may help in lowering the pulmonary pressures by causing sustained left ventricular unloading. SUMMARY: Pulmonary hypertension in the context of left heart disease is the most common form of pulmonary hypertension encountered in clinical practice and is associated with worse prognosis in patients being considered for cardiac transplantation. Therapies targeting left ventricular unloading, as well as pulmonary vascular remodeling, are being increasingly studied and used in daily practice.

Optimization of water curing for the preservation of chestnuts (Castanea sativa Mill.) and evaluation of microbial dynamics during process.

Chestnuts are very perishable fruits, whose quality may be compromised during postharvest handling. Damage can be caused both by insects and fungi. Water curing, a commonly used postharvest method, is based on soaking fruits in water typically for about one week. Factors that affect effectiveness of water curing have only been explained partially. A decrease in pH, likely imputable to a light fermentation caused by lactic acid bacteria, may inhibit the growth of moulds. In this study a Lactobacillus pentosus strain was selected for its ability to inhibit fungi, and used as a starter culture during water curing. As second goal, a reduction of the environmental impact of the process was evaluated by using water that had been re-cycled from a previous curing treatment. Experiments were performed on pilot as well as on farm scale. In all trials, microbial dynamics were evaluated by means of a polyphasic approach including conventional and molecular-based analyses. According to results, the employment of an adjunct culture appears as a very promising opportunity. Even if no reduction in the duration of the process was achieved, waters exhibited a minor microbial complexity and fruits did not lose the natural lustre after the process.

Technological and Safety Characterization of Coagulase-Negative Staphylococci Isolated from Sardinian Fermented Sausage Made by Ovine Meat.

Ripened sheep sausages are widely consumed in Italy, particularly in Sardinia. Despite their driving role in flavor and color development, coagulase-negative staphylococci in these products have been rarely investigated. A total of 70 CoNS cultures isolated from Sardinian sheep sausages were characterized by rep-PCR and M13-RAPD typing and identified by 16S rDNA sequencing. S. xylosus and S. equorum accounted for more than 70% of the total isolates, whilst S. pasteuri (8.5%), S. succinus (2.8%), and S. haemolyticus (2.8%) were less represented. The genes encoding the synthesis of putrescine, tyramine, cadaverine, and histamine were evaluated by PCR. None of the strains hosted genes for decarboxylases, except one S. pasteuri strain that was potentially a tyramine-producer. Antibiotic resistance was evaluated, along with nitrate reductase, lipolytic, and proteolytic activity, in a pool of selected cultures. Resistance to the primary antibiotics was rather widespread. S. xylosus, S. equorum, and S. pasteuri strains were all resistant to amoxicillin and kanamycin. S. equorum strains were sensitive to all tested antibiotics. S. xylosus strains were all resistant to penicillin B. Conversely, all S. pasteuri strains were resistant to both ampicillin and penicillin B, and four out of five strains exhibited tetracycline resistance. The high variability in the production of sheep sausages makes the search for adjunct cultures of crucial relevance. According to this perspective, the characterization of the autochthonous CSN population represents the first step to approach a starter selection.

Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host.

Glioblastoma (GBM) is the most common primary brain tumor in adults with a poor prognosis despite aggressive therapy. A recent, retrospective clinical study found that administering Temozolomide in the morning increased patient overall survival by 6 months compared to evening. Here, we tested the hypothesis that daily host signaling regulates tumor growth and synchronizes circadian rhythms in GBM. We found daily Dexamethasone promoted or suppressed GBM growth depending on time of day of administration and on the clock gene, Bmal1. Blocking circadian signals, like VIP or glucocorticoids, dramatically slowed GBM growth and disease progression. Finally, mouse and human GBM models have intrinsic circadian rhythms in clock gene expression in vitro and in vivo that entrain to the host through glucocorticoid signaling, regardless of tumor type or host immune status. We conclude that GBM entrains to the circadian circuit of the brain, which modulates its growth through clockcontrolled cues, like glucocorticoids.

The Role of Palliative Care Consultation in Withdrawal of Life-Sustaining Treatment among ICU Patients Receiving Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO): A Retrospective Case-Control Study.

Background: Extracorporeal membrane oxygenation (ECMO) has extended the survivability of critically ill patients beyond their unsupported prognosis and has widened the timeframe for making an informed decision about the goal of care. However, an extended time window for survival does not necessarily translate into a better outcome and the sustaining treatment is ultimately withdrawn in many patients. Emerging evidence has implicated the determining role of palliative care consult (PCC) in direction of the care that critically ill patients receive. Objective: To evaluate the impact of PCC in withdrawal of life-sustaining treatment (WOLST) among critically ill patients, who were placed on venovenous ECMO (VV-ECMO) at the intensive care unit (ICU) of a tertiary care hospital. Methods: In a retrospective observational study, electronic medical records of 750 patients admitted to the ICU of our hospital between January 1, 2015, and October 31, 2021, were reviewed. Data was collected for patients on VV-ECMO, for whom WOLST was withdrawn during the ICU stay. Clinical characteristics and the underlying reasons for WOLST were compared between those who received PCC (PCC group) and those who did not (non-PCC group). Results: A total of 95 patients were included in our analysis, 63 in the PCC group and 32 in the non-PCC group. The average age of the study population was 48.8 ± 12.6 years, and 64.2% were male. There was no statistically significant difference between the two groups in terms of demographics or clinical characteristics at the time of ICU admission. The average duration of ICU stay and VV-ECMO were 14.1 ± 19.9 days and 9.4 ± 16.6 days, respectively. The number of PCC visits was correlated with the length of ICU stay. The average duration of ICU stay (40.3 ± 33.2 days vs 27.8 ± 19.3 days, P = .05) and ECMO treatment (31.9 ± 27 days vs 18.6 ± 16.1 days, P = .01) were significantly longer in patients receiving PCC than those not receiving PCC. However, the frequency of life sustaining measures or the underlying reasons for WOLST did not significantly differ between the two groups (P > .05). Conclusion: Among ICU patients requiring ECMO support, longer duration of ICU stay and treatment with a higher number of life-sustaining measures seemed to be correlated with the number of PCC visits. The underlying reasons for WOLST seem not to be affected by PCC.