A devastating blow: personal reflections on Argentina's scientific decline.

As an Argentine scientist, the defunding of CONICET and INTA feels like a blow to progress and our future. Despite free education, these cuts force talented researchers to seek opportunities abroad. Argentina's history of scientific achievement, from Nobel Prizes to COVID-19 vaccines, is at risk. Defunding science weakens our ability to solve problems and compete globally.

Specific nanoprobe design for MRI: Targeting laminin in the blood-brain barrier to follow alteration due to neuroinflammation.

Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1ß (IL-1ß) for 3 and 24 hours. IL-1ß for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.

Analysis of the elderly pedestrian traffic accidents in urban scenarios: the case of the Spanish municipalities.

As the elderly population grows, there is a greater concern for their safety on the roads. This is particularly important for elderly pedestrians who are more vulnerable to accidents. In Spain, one of the most aged countries in the world, the elderly accounted for 70% of all pedestrian deaths in 2019. In this study, the focus was on analysing the occurrence of elderly pedestrian-vehicle collisions in Spanish municipalities and how it is related to the built environment. The study used the hurdle negative binomial model to analyse the number of elderly and non-elderly pedestrian accidents per municipality in 2016-2019. The exploratory analysis showed that cities above 50,000 inhabitants were safer for the elderly, and larger provincial capitals had lower elderly pedestrian traffic accident rates. The occurrence of all pedestrian traffic accidents was linked to the socio-demographic features. For elderly pedestrians, land use was found to be influential, with a lower proportion of land covered by manufacturing and service activities linked to a smaller number of accidents. Results showed that improving road safety for older pedestrians may not necessarily compromise the situation for the rest of population. Hence, policymakers should focus on infrastructure improvements adapted to the needs of elderly pedestrians.

Oscillometric devices vs. arterial Doppler in measuring the ankle-arm index for the diagnosis of peripheral arterial disease. / Dispositivos oscilométricos frente a Doppler arterial en la medida del índice tobillo-brazo para el diagnóstico de la enfermedad arterial periférica.

INTRODUCTION: Peripheral arterial disease is a marker of vascular damage that is diagnosed by measuring the ankle-brachial index. The aim of this study was to determine the validity and agreement of the MESI ABPI-MD and Microlife WatchBP® office-ABI oscillometric devices with respect to the gold standard arterial Doppler. MATERIALS AND METHODS: Observational, cross-sectional, descriptive study of inpatients who underwent ABI measurement with the three devices. Values are considered normal between 1-1.4, indeterminate between 0.91-0.99 and pathological ≤0.9 and >1.4. RESULTS: A total of 187 patients (54.4% male) with a mean age of 66 years were included. The Doppler results were inferior to those of the oscillometric devices (median [IQR] 1.1 [0.2] vs. 1.2 [0.2], P<.05), with no significant differences between the automated devices (P=.29 for the right lower limb and P=.342 for the left lower limb). Both devices had high specificity (96.5-99.2%) and low sensitivity (29.5-45.4%). The correlation of the results was good-moderate for MESI and moderate for Microlife. The agreement between the two was acceptable-moderate. CONCLUSION: Automated oscillometric devices could be useful in asymptomatic patients as an alternative to arterial Doppler.

Long-term follow-up of total hip arthroplasty using polyethylene-ceramic composite (sandwich) liner.

INTRODUCTION: Ceramic-on-ceramic bearings have been widely used since their introduction in the 1970s. First-generation ceramics have very high fracture (breakage) rates. To overcome this, in the 1990s, modular cotyloid insert designs were developed, consisting of a ceramic and polyethylene composite (sandwich-type) liner; however, high implant fracture rates were observed in the medium term. We aimed to estimate the cumulative incidences of revision surgery (implant failure) and implant failure due to fractures, survival rates (time-to-revision surgery and time-to-fracture), and the long-term clinical and radiological outcomes in our series. METHODS: This was an observational, longitudinal, ambispective, single-centre study based on patients who underwent primary total hip arthroplasty (THA) using a sandwich-type liner (Cerasul), only available in our tertiary hospital between January 1999 and December 2002. Cumulative incidences were estimated and the 95% confidence interval (95% CI) was calculated. The Kaplan-Meier method was used to assess the time-to-revision surgery and time-to-fracture. RESULTS: 54 patients (49 men) were included, accounting for 59 sandwich-type linear implants. The mean (range) age was 47.4 (22-57) years. The primary THA indications were osteoarthritis (28 patients), osteonecrosis (14), childhood pathology sequelae (11), and inflammatory arthritis (6). The cumulative incidence of revision surgery by implants was 8.5% (5/59, 95% CI, 3.5-19.2%), 9.3% by patients (5/54, 95% CI, 4.0-19.9%), and 5.1% by implant fractures (3/59, 95%CI, 1.7-13.9%). The median (Interquartile Range, IQR) time-to-revision surgery was 158 (72.5-161) months, and the time to fracture was 182 (138-215) months. All primary THAs had good clinical and long-term survival outcomes. All implants had signs of solid fixation. CONCLUSIONS: After a 20-year follow-up period, the polyethylene-ceramic sandwich-type liner showed a long survival rate and low cumulative incidence of implant fracture; however, implant fractures remain the main complication. Orthopaedic surgeons should be aware that some patients still have this type of prosthesis and must be capable of responding quickly if a fracture occurs.

In vitro effect of diazoxon on cell signaling and second messengers in Nile tilapia (Oreochromis niloticus) leukocytes.

The physiological and molecular responses of leukocytes are altered by organophosphate pesticides (OPs). Some reports have shown that diazinon (DZN) causes immunotoxic effects; diazoxon (DZO), the oxon metabolite of DZN, is attributed to influence the immune response by affecting the leukocyte cholinergic system. In this study, the in vitro effects of DZO on molecules involved in cell signaling (cAMP, IP3, DAG, JAK1, and STAT3), which play a crucial role in the activation, differentiation, and survival of leukocytes, were evaluated. Data indicate that DZO leads to a decrease in cAMP concentration and an increase in basal IP3 levels. However, DZO does not affect basal levels of JAK1 and STAT3 phosphorylation. Instead, DZO inhibits leukocyte responsiveness to PMA and ionomycin, substances that, under normal conditions, enhance JAK/STAT signaling. These findings demonstrate that DZO significantly affects key molecular parameters related to cell signaling.

Single clonal tracking on biomimetic microtextured platforms for real-time guided migration analysis of myeloid-derived suppressor cell dissemination characteristics ex vivo.

Current strategies to undermine the deleterious influence of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TME) are lacking effective clinical solutions, in large part, due to insufficient knowledge on susceptible cellular and molecular targets. We describe here the application of biomimetic microfabricated platforms designed to analyze migratory phenotypes of MDSCs in the tumor niche ex vivo, which may enable accelerated therapeutic discovery. By mimicking the guided structural cues present in the physiological architecture of the TME, aligned microtopography substrates can elucidate potential interventions on migratory phenotypes of MDSCs at the single clonal level. Coupled with cellular and molecular biology analysis tools, our approach employs real-time tracking analysis of cell motility to probe the dissemination characteristics of MDSCs under guided migration conditions. These methods allow us to identify cellular subpopulations of interest based on their disseminative and suppressive capabilities. By doing so, we illustrate the potential of applying microscale engineering tools, in concert with dynamic live cell imaging and bioanalysis methods to uncover novel exploitable motility targets for advancing cancer therapy discovery. The inherent simplicity and extended application to a variety of contexts in tumor-associated cell migration render this method widely accessible to existing biological laboratory conditions and interests.

Do the humeral radiographic changes at 5-year follow-up affect the clinical outcomes of press-fit humeral stems in primary reverse shoulder arthroplasties?

INTRODUCTION: The purposes of this study were to analyze and compare the functional outcomes and radiological changes around the press-fit humeral components in two contemporary medialized reverse total shoulder arthroplasty (RTSA) systems at a minimum of 5-year follow-up. MATERIALS AND METHODS: Between December 2003 and December 2015, 249 consecutive RTSAs were performed at our hospital. Of these, 68 primary uncemented RTSA met our inclusion criteria. The Constant-Murley score (CMS), the modified Constant score, a visual analog scale (VAS) and active shoulder range of motion (ROM) were measured pre- and postoperatively. Radiological assessment was performed by plain radiographs at a minimum of 5 years postoperatively. RESULTS: At a mean follow-up of 80.2 months, there was no significant difference (p = .59) between the postoperative functional scores and range of motion of the two groups (Delta Xtend and Lima SMR). Radiological data of stress-shielding were observed in 38 patients (55.9%) being slightly more frequent in the Lima SMR group (21 patients) than in the Delta Xtend group (17 patients) (p = .62). CONCLUSIONS: Our study shows that the good functional results are similar between the two uncemented RTSA systems used and that they do not depend on the presence of radiological changes (stress-shielding) in the humeral stem at a minimum 5-year follow-up.

Implementation of pharmaceutical alternatives to a toxic drug supply in British Columbia: A mixed methods study.

BACKGROUND: North America has been in an unrelenting overdose crisis for almost a decade. British Columbia (BC), Canada declared a public health emergency due to overdoses in 2016. Risk Mitigation Guidance (RMG) for prescribing pharmaceutical opioids, stimulants and benzodiazepine alternatives to the toxic drug supply ("safer supply") was implemented in March 2020 in an attempt to reduce harms of COVID-19 and overdose deaths in BC during dual declared public health emergencies. Our objective was to describe early implementation of RMG among prescribers in BC. METHODS: We conducted a convergent mixed methods study drawing population-level linked administrative health data and qualitative interviews with 17 prescribers. The Consolidated Framework for Implementation Research (CFIR) informs our work. The study utilized seven linked databases, capturing the characteristics of prescribers for people with substance use disorder to describe the characteristics of those prescribing under the RMG using univariate summary statistics and logistic regression analysis. For the qualitative analysis, we drew on interpretative descriptive methodology to identify barriers and facilitators to implementation. RESULTS: Analysis of administrative databases demonstrated limited uptake of the intervention outside large urban centres and a highly specific profile of urban prescribers, with larger and more complex caseloads associated with RMG prescribing. Nurse practitioners were three times more likely to prescribe than general practitioners. Qualitatively, the study identified five themes related to the five CFIR domains: 1) RMG is helpful but controversial; 2) Motivations and challenges to prescribing; 3) New options and opportunities for care but not enough to 'win the arms race'; 4) Lack of implementation support and resources; 5) Limited infrastructure. CONCLUSIONS: BC's implementation of RMG was limited in scope, prescriber uptake and geographic scale up. Systemic, organizational and individual barriers and facilitators point to the importance of engaging professional regulatory colleges, implementation planning and organizational infrastructure to ensure effective implementation and adaptation to context.

Functional proteomics of colon cancer Consensus Molecular Subtypes.

BACKGROUND: The Colorectal Cancer Subtyping Consortium established four Consensus Molecular Subtypes (CMS) in colorectal cancer: CMS1 (microsatellite-instability [MSI], Immune), CMS2 (Canonical, epithelial), CMS3 (Metabolic), and CMS4 (Mesenchymal). However, only MSI tumour patients have seen a change in their disease management in clinical practice. This study aims to characterise the proteome of colon cancer CMS and broaden CMS's clinical utility. METHODS: One-hundred fifty-eight paraffin samples from stage II-III colon cancer patients treated with adjuvant chemotherapy were analysed through DIA-based mass-spectrometry proteomics. RESULTS: CMS1 exhibited overexpression of immune-related proteins, specifically related to neutrophils, phagocytosis, antimicrobial response, and a glycolytic profile. These findings suggested potential therapeutic strategies involving immunotherapy and glycolytic inhibitors. CMS3 showed overexpression of metabolic proteins. CMS2 displayed a heterogeneous protein profile. Notably, two proteomics subtypes within CMS2, with different protein characteristics and prognoses, were identified. CMS4 emerged as the most distinct group, featuring overexpression of proteins related to angiogenesis, extracellular matrix, focal adhesion, and complement activation. CMS4 showed a high metastatic profile and suggested possible chemoresistance that may explain its worse prognosis. CONCLUSIONS: DIA proteomics revealed new features for each colon cancer CMS subtype. These findings provide valuable insights into potential therapeutic targets for colorectal cancer subtypes in the future.

Impact of sex on humoral immunity with live influenza B virus vaccines in mice.

Influenza B virus (FLUBV) poses a significant infectious threat, with frequent vaccine mismatch limiting its effectiveness. Our previous work investigated the safety and efficacy of modified live attenuated FLUBV vaccines with rearranged genomes (FluB-RAM and FluB-RANS) or a temperature-sensitive PB1 segment with a C-terminal HA tag (FluB-att). In this study, we compared the immune responses of female and male DBA/2J mice vaccinated with these vaccines, including versions containing a chimeric HA segment with an N-terminal IgA-inducing peptide (IGIP). Importantly, both recombinant viruses with and without IGIP remained genetically stable during egg passage. We found that introducing IGIP strengthened vaccine attenuation, particularly for FluB-RAM/IGIP. Prime-boost vaccination completely protected mice against lethal challenge with a homologous FLUBV strain. Notably, recombinant viruses induced robust neutralizing antibody responses (hemagglutination inhibition titers ≥40) alongside antibodies against NA and NP. Interestingly, female mice displayed a consistent trend of enhanced humoral and cross-reactive IgG and IgA responses against HA, NA, and NP compared to male counterparts, regardless of the vaccine used. However, the presence of IGIP generally led to lower anti-HA responses but higher anti-NA and anti-NP responses, particularly of the IgA isotype. These trends were further reflected in mucosal and serological responses two weeks after challenge, with clear distinctions based on sex, vaccine backbone, and IGIP inclusion. These findings hold significant promise for advancing the development of universal influenza vaccines.

Nucleoprotein reassortment enhanced transmissibility of H3 1990.4.a clade influenza A virus in swine.

The increased detection of H3 C-IVA (1990.4.a) clade influenza A viruses (IAVs) in US swine in 2019 was associated with a reassortment event to acquire an H1N1pdm09 lineage nucleoprotein (pdmNP) gene, replacing a TRIG lineage NP (trigNP). We hypothesized that acquiring the pdmNP conferred a selective advantage over prior circulating H3 viruses with a trigNP. To investigate the role of NP reassortment in transmission, we identified two contemporary 1990.4.a representative strains (NC/19 and MN/18) with different evolutionary origins of the NP gene. A reverse genetics system was used to generate wild-type (wt) strains and swap the pdm and TRIG lineage NP genes, generating four viruses: wtNC/19-pdmNP, NC/19-trigNP, wtMN/18-trigNP, and MN/18-pdmNP. The pathogenicity and transmission of the four viruses were compared in pigs. All four viruses infected 10 primary pigs and transmitted to five indirect contact pigs per group. Pigs infected via contact with MN/18-pdmNP shed virus 2 days earlier than pigs infected with wtMN/18-trigNP. The inverse did not occur for wtNC/19-pdmNP and NC/19-trigNP. This suggests that pdmNP reassortment resulted in a combination of genes that improved transmission efficiency when paired with the 1990.4.a hemagglutinin (HA). This is likely a multigenic trait, as replacing the trigNP gene did not diminish the transmission of a wild-type IAV in swine. This study demonstrates how reassortment and evolutionary change of internal genes can result in more transmissible viruses that influence HA clade detection frequency. Thus, rapidly identifying novel reassortants paired with dominant hemagglutinin/neuraminidase may improve the prediction of strains to include in vaccines.IMPORTANCEInfluenza A viruses (IAVs) are composed of eight non-continuous gene segments that can reassort during coinfection of a host, creating new combinations. Some gene combinations may convey a selective advantage and be paired together preferentially. A reassortment event was detected in swine in the United States that involved the exchange of two lineages of nucleoprotein (NP) genes (trigNP to pdmNP) that became a predominant genotype detected in surveillance. Using a transmission study, we demonstrated that exchanging the trigNP for a pdmNP caused the virus to shed from the nose at higher levels and transmit to other pigs more rapidly. Replacing a pdmNP with a trigNP did not hinder transmission, suggesting that transmission efficiency depends on interactions between multiple genes. This demonstrates how reassortment alters IAV transmission and that reassortment events can provide an explanation for why genetically related viruses with different internal gene combinations experience rapid fluxes in detection frequency.

Amino acid 138 in the HA of a H3N2 subtype influenza A virus increases affinity for the lower respiratory tract and alveolar macrophages in pigs.

Influenza A virus (FLUAV) infects a wide range of hosts and human-to-swine spillover events are frequently reported. However, only a few of these human viruses have become established in pigs and the host barriers and molecular mechanisms driving adaptation to the swine host remain poorly understood. We previously found that infection of pigs with a 2:6 reassortant virus (hVIC/11) containing the hemagglutinin (HA) and neuraminidase (NA) gene segments from the human strain A/Victoria/361/2011 (H3N2) and internal gene segments of an endemic swine strain (sOH/04) resulted in a fixed amino acid substitution in the HA (A138S, mature H3 HA numbering). In silico analysis revealed that S138 became predominant among swine H3N2 virus sequences deposited in public databases, while 138A predominates in human isolates. To understand the role of the HA A138S substitution in the adaptation of a human-origin FLUAV HA to swine, we infected pigs with the hVIC/11A138S mutant and analyzed pathogenesis and transmission compared to hVIC/11 and sOH/04. Our results showed that the hVIC/11A138S virus had an intermediary pathogenesis between hVIC/11 and sOH/04. The hVIC/11A138S infected the upper respiratory tract, right caudal, and both cranial lobes while hVIC/11 was only detected in nose and trachea samples. Viruses induced a distinct expression pattern of various pro-inflammatory cytokines such as IL-8, TNF-α, and IFN-ß. Flow cytometric analysis of lung samples revealed a significant reduction of porcine alveolar macrophages (PAMs) in hVIC/11A138S-infected pigs compared to hVIC/11 while a MHCIIlowCD163neg population was increased. The hVIC/11A138S showed a higher affinity for PAMs than hVIC/11, noted as an increase of infected PAMs in bronchoalveolar lavage fluid (BALF), and showed no differences in the percentage of HA-positive PAMs compared to sOH/04. This increased infection of PAMs led to an increase of granulocyte-monocyte colony-stimulating factor (GM-CSF) stimulation but a reduced expression of peroxisome proliferator-activated receptor gamma (PPARγ) in the sOH/04-infected group. Analysis using the PAM cell line 3D4/21 revealed that the A138S substitution improved replication and apoptosis induction in this cell type compared to hVIC/11 but at lower levels than sOH/04. Overall, our study indicates that adaptation of human viruses to the swine host involves an increased affinity for the lower respiratory tract and alveolar macrophages.

Low-Scaling GW Algorithm Applied to Twisted Transition-Metal Dichalcogenide Heterobilayers.

The GW method is widely used for calculating the electronic band structure of materials. The high computational cost of GW algorithms prohibits their application to many systems of interest. We present a periodic, low-scaling, and highly efficient GW algorithm that benefits from the locality of the Gaussian basis and the polarizability. The algorithm enables G0W0 calculations on a MoSe2/WS2 bilayer with 984 atoms per unit cell, in 42 h using 1536 cores. This is 4 orders of magnitude faster than a plane-wave G0W0 algorithm, allowing for unprecedented computational studies of electronic excitations at the nanoscale.

Photooxidation driven formation of Fe-Au linked ferrocene-based single-molecule junctions.

Metal-metal contacts, though not yet widely realized, may provide exciting opportunities to serve as tunable and functional interfaces in single-molecule devices. One of the simplest components which might facilitate such binding interactions is the ferrocene group. Notably, direct bonds between the ferrocene iron center and metals such as Pd or Co have been demonstrated in molecular complexes comprising coordinating ligands attached to the cyclopentadienyl rings. Here, we demonstrate that ferrocene-based single-molecule devices with Fe-Au interfacial contact geometries form at room temperature in the absence of supporting coordinating ligands. Applying a photoredox reaction, we propose that ferrocene only functions effectively as a contact group when oxidized, binding to gold through a formal Fe3+ center. This observation is further supported by a series of control measurements and density functional theory calculations. Our findings extend the scope of junction contact chemistries beyond those involving main group elements, lay the foundation for light switchable ferrocene-based single-molecule devices, and highlight new potential mechanistic function(s) of unsubstituted ferrocenium groups in synthetic processes.

FLUAV RAM-IGIP: A modified live influenza virus vaccine that enhances humoral and mucosal responses against influenza.

Current influenza A vaccines fall short, leaving both humans and animals vulnerable. To address this issue, we have developed attenuated modified live virus (MLV) vaccines against influenza using genome rearrangement techniques targeting the internal gene segments of FLUAV. The rearranged M2 (RAM) strategy involves cloning the M2 ORF downstream of the PB1 ORF in segment 2 and incorporating multiple early stop codons within the M2 ORF in segment 7. Additionally, the IgA-inducing protein (IGIP) coding region was inserted into the HA segment to further attenuate the virus and enhance protective mucosal responses. RAM-IGIP viruses exhibit similar growth rates to wild type (WT) viruses in vitro and remain stable during multiple passages in cells and embryonated eggs. The safety, immunogenicity, and protective efficacy of the RAM-IGIP MLV vaccine against the prototypical 2009 pandemic H1N1 strain A/California/04/2009 (H1N1) (Ca/04) were evaluated in Balb/c mice and compared to a prototypic cold-adapted live attenuated virus vaccine. The results demonstrate that the RAM-IGIP virus exhibits attenuated virulence in vivo. Mice vaccinated with RAM-IGIP and subsequently challenged with an aggressive lethal dose of the Ca/04 strain exhibited complete protection. Analysis of the humoral immune response revealed that the inclusion of IGIP enhanced the production of neutralizing antibodies and augmented the antibody-dependent cellular cytotoxicity response. Similarly, the RAM-IGIP potentiated the mucosal immune response against various FLUAV subtypes. Moreover, increased antibodies against NP and NA responses were observed. These findings support the development of MLVs utilizing genome rearrangement strategies in conjunction with the incorporation of immunomodulators. IMPORTANCE: Current influenza vaccines offer suboptimal protection, leaving both humans and animals vulnerable. Our novel attenuated MLV vaccine, built by rearranging FLUAV genome segments and incorporating the IgA-inducing protein, shows promising results. This RAM-IGIP vaccine exhibits safe attenuation, robust immune responses, and complete protection against lethal viral challenge in mice. Its ability to stimulate broad-spectrum humoral and mucosal immunity against diverse FLUAV subtypes makes it a highly promising candidate for improved influenza vaccines.

Swine influenza A virus isolates containing the pandemic H1N1 origin matrix gene elicit greater disease in the murine model.

Since the 1990s, endemic North American swine influenza A viruses (swFLUAVs) contained an internal gene segment constellation, the triple reassortment internal gene (TRIG) cassette. In 2009, the H1N1 pandemic (pdmH1N1) virus spilled back into swine but did not become endemic. However, the pdmH1N1 contributed the matrix gene (pdmM) to the swFLUAVs circulating in the pig population, which replaced the classical swine matrix gene (swM) found in the TRIG cassette, suggesting the pdmM has a fitness benefit. Others have shown that swFLUAVs containing the pdmM have greater transmission efficiency compared to viruses containing the swM gene segment. We hypothesized that the matrix (M) gene could also affect disease and utilized two infection models, resistant BALB/c and susceptible DBA/2 mice, to assess pathogenicity. We infected BALB/c and DBA/2 mice with H1 and H3 swFLUAVs containing the swM or pdmM and measured lung virus titers, morbidity, mortality, and lung histopathology. H1 influenza strains containing the pdmM gene caused greater morbidity and mortality in resistant and susceptible murine strains, while H3 swFLUAVs caused no clinical disease. However, both H1 and H3 swFLUAVs containing the pdmM replicated to higher viral titers in the lungs and pdmM containing H1 viruses induced greater histological changes compared to swM H1 viruses. While the surface glycoproteins and other gene segments may contribute to swFLUAV pathogenicity in mice, these data suggest that the origin of the matrix gene also contributes to pathogenicity of swFLUAV in mice, although we must be cautious in translating these conclusions to their natural host, swine. IMPORTANCE: The 2009 pandemic H1N1 virus rapidly spilled back into North American swine, reassorting with the already genetically diverse swFLUAVs. Notably, the M gene segment quickly replaced the classical M gene segment, suggesting a fitness benefit. Here, using two murine models of infection, we demonstrate that swFLUAV isolates containing the pandemic H1N1 origin M gene caused increased disease compared to isolates containing the classical swine M gene. These results suggest that, in addition to other influenza virus gene segments, the swFLUAV M gene segment contributes to pathogenesis in mammals.

Antiproliferative and Antimigratory Activity of Poly-gallic Acid in Cancer Cell Lines.

BACKGROUND/AIM: Enzyme-mediated grafting of poly (gallic acid) (PGAL) and L-arginine and a-L-lysine onto PGAL produces reactive oxygen species (ROS)-suppressor multiradical molecules with low cytotoxicity, high thermostability and water solubility with cancer treatment potential. This study examined the anticancer effects of these molecules in hepatic (HepG2, ATCC HB-8065), breast (MCF7, ATCC HTB-22), and prostate (PC-3, ATCC CRL-1435 and DU 145, ATCC HTB-81) cancer cell lines, as well as in fibroblasts from healthy human skin as control cells. MATERIALS AND METHODS: PGAL was synthesized by the oxidative polymerization of the naturally abundant GA using laccase from Trametes versicolor. Insertions of amino acids L-arginine and α-L-lysine on the PGAL chain were carried out by microwave. The cells of dermal fibroblast (Fb) were obtained from primary skin cultures and isolated from skin biopsies. The cancer cells lines of hepatic (HepG2), breast (MCF7), and prostate (PC-3, DU 145) were obtained from ATCC. The viability of the cancer cells and the primary culture was obtained by the MTT assay. Proliferation was demonstrated by crystal violet assay. Cell migration was determined by Wound healing assay. Finally, cell cycle analysis was carried out with cells. RESULTS: The results show that 200 µg/ml of PGAL cultured in vitro with prostate cancer cells decreased viability, proliferation, and migration, as well as arrested cells in the G1 and S phases of the cell cycle. In contrast, the dermal fibroblasts and the hepatic line remained unaffected. The random grafting of L-Arg and a-L-Lys onto the PGAL chain also decreased the viability of prostate cancer cells. CONCLUSION: PGAL and PGAL-grafted amino acids are potential adjuvants for prostate cancer treatment, with improved physicochemical characteristics compared to GA.

The postsurgical pancreas. / Das postoperative Pankreas.

BACKGROUND: Partial pancreatic resections are among the most complex surgical procedures in visceral tumor medicine and are associated with a high postoperative morbidity with a complication rate of 40-50 % of patients even in specialized centers. METHODS: Description of typical surgical resection procedures and the resulting postoperative anatomy, typical normal postoperative findings, common postoperative complications, and radiological findings. RESULTS AND CONCLUSION: CT is the most appropriate imaging technique for rapid and standardized visualization of postoperative anatomy and detection of clinically suspected complications after partial pancreatic resections. The most common complications are delayed gastric emptying, pancreatic fistula, acute pancreatitis, bile leakage, abscess, and hemorrhage. Radiologists must identify the typical surgical procedures, the postoperative anatomy, and normal postoperative findings as well as possible postoperative complications and know interventional treatment methods for common complications. KEY POINTS: · Morbidity after pancreatic surgery remains high.. · CT is the best method for visualizing postoperative anatomy and is used for early detection of complications.. · Pancreatic fistula is the most common relevant complication after pancreatic resection.. · The ability of a center to manage complications is crucial to ensure the success of therapy.. CITATION FORMAT: · Fischbach R, Peller M, Perez D et al. The postsurgical pancreas. Fortschr Röntgenstr 2024; DOI: 10.1055/a-2254-5824.