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Abstract Background Due to increasing older populations worldwide, injuries, disabilities and deaths caused by falls among the elderly represent a growing human and societal problem. We aimed to improve health among men of at least 70 years of age with low‐normal to low testosterone and mobility problems by using testosterone undecanoate (TU) injections, progressive strength training, and oral supplements of vitamin D, calcium and protein. Methods This was a single‐centre, randomized, placebo‐controlled, double‐blind trial with 148 older men with a median age of 77 (73–81) years, testosterone levels at median 8 (5–9) nmol/L (full range from 1.1 to 12.9 nmol/L) and mobility problems, recruited at University Hospital of Copenhagen, Herlev Hospital, Denmark. Participants were randomized into four arms for 20 weeks: (1) TU therapy (n = 37); (2) progressive resistance training with supplements of calcium, vitamin D and protein (n = 36); (3) both interventions combined (n = 36); or (4) no intervention (n = 39). The main outcome measure was the 30‐s chair stand test, due to test performance correlating with the risk of serious fall injuries and lower extremity muscle strength. Outcome measurements were performed at baseline and after 20 weeks. Results After the intervention, the combination group receiving progressive resistance training, TU and supplements achieved a median score of 13 (11–15) compared to the control group at 10 (0–14) in the 30‐s chair stand test (P = 0.003). This median improvement of 3.0 was clinically important. Compared to the control group, participants in the combination group also increased quality of life (P

Abstract Adhesins are crucial factors in the virulence of bacterial pathogens such as Escherichia coli. However, to date no resources have been dedicated to the detailed analysis of E. coli adhesins. Here, we provide adhesiomeR software that enables characterization of the complete adhesin repertoire, termed the adhesiome. AdhesiomeR incorporates the most comprehensive database of E. coli adhesins and facilitates an extensive analysis of adhesiome. We demonstrate that adhesiomeR achieves 98% accuracy when compared with experimental analyses. Based on analysis of 15,000 E. coli genomes, we define novel adhesiome profiles and clusters, providing a nomenclature for a unified comparison of E. coli adhesiomes.

Abstract Introduction Tranexamic acid has been widely used in plastic surgery. However, its efficacy has yet to be fully established. This meta-analysis aimed to determine its effectiveness in aesthetic plastic surgery. Methods Following PRISMA guidelines, we conducted a meta-analysis of prospective randomised clinical trials that compared the effects of topical or systematic administration of tranexamic acid versus the control group in aesthetic plastic surgeries. The study was registered on the International Register of Systematic Reviews (PROSPERO) and is available online ( www.crd.york.uk/prospero , CRD42023492585). Results Eleven studies encompassing 960 patients were included for the synthesis after critical evaluation. Systematic (MD − 18.05, 95% Cl, − 22.01, − 14.09, p

ABSTRACT Phage therapy appears to be a promising approach to tackle multidrug-resistant bacteria, including staphylococci. However, most anti-staphylococcal phages have been characterized in Staphylococcus aureus, while a limited number of studies investigated phage activity against S. epidermidis. We studied the potential of phage training to extend the host range of two types of anti-S. aureus phages against S. epidermidis isolates. The Appelmans protocol was applied to a mixture of Kayvirus and a mixture of Silviavirus phages repeatedly exposed to seven S. epidermidis strains representative of nosocomial-associated sequence types (ST), including the world-wide disseminated ST2. We observed increased activity only for the Kayvirus mixture against two of these strains (ST2 or ST35). Phage subpopulations isolated from the training mixture using these two strains (five/strain) exhibited different evolved phenotypes, active only against their isolation strain or strains of the same ST. Of note, 16/47 ST2 strains were susceptible to one of the groups of trained phages. A comparative genomic analysis of ancestral and trained phage genomes, conducted to identify potential bacterial determinants of such specific activity, found numerous recombination events between two of the three ancestors. However, a small number of trained phage genes had nucleotide sequence modifications impacting the corresponding protein compared to ancestral phages, two to four of them per phage genome being specific of each group of phage subpopulations exhibiting different host range. The results suggest that anti-S. aureus phages can be adapted to S. epidermidis isolates but with inter- and intra-ST specificity.ImportanceS. epidermidis is increasingly recognized as a threat for public health. Its clinical importance is notably related to multidrug resistance. Phage therapy is one of the most promising alternative therapeutic strategies to antibiotics. Nonetheless, only very few phages active against this bacterial species have been described. In the present study, we showed that phage training can be used to extend the host range of polyvalent Kayvirus phages within the Staphylococcus genera to include S. epidermidis species. In the context of rapid development of phage therapy, in vitro forced adaptation of previously characterized phages could be an appealing alternative to fastidious repeated isolation of new phages to improve the therapeutic potential of a phage collection.

Colorectal cancer is the third most common cancer worldwide and the second cause of death from malignant tumors. Colorectal cancers are treated with surgery, chemotherapy, gene therapy and immunotherapy. PD-1 and PD-L1 proteins have recently been considered as potential targets of anticancer therapy in colorectal cancer. The aim of this study was to evaluate the association of immunohistochemical expression of PD-1 and PD-L1 proteins in colorectal cancer patients with selected clinical and morphological parameters and their survival. Ninety-eight cases of colorectal cancer were studied. Immunohistochemistry was used to evaluate the expression of PD-1 and PD-L1 proteins. Correlations were found between the expression of PD-L1 protein in lymphocytes and lack of lymph node metastases and a lower clinical stage. There was also a correlation between PD-L1 protein expression in cancer cells and a higher grade of histological malignancy.

Abstract Adaptation of avian pathogenic E. coli (APEC) to changing host environments including virulence factors expression is vital for disease progression. FdeC is an autotransporter adhesin that plays a role in uropathogenic Escherichia coli (UPEC) adhesion to epithelial cells. Expression of fdeC is known to be regulated by environmental conditions in UPEC and Shiga toxin-producing E. coli (STEC). The observation in a previous study that an APEC strain IMT5155 in which the fdeC gene was disrupted by a transposon insertion resulted in elevated adhesion to chicken intestinal cells prompted us to further explore the role of fdeC in infection. We found that the fdeC gene prevalence and FdeC variant prevalence differed between APEC and nonpathogenic E. coli genomes. Expression of the fdeC gene was induced at host body temperature, an infection relevant condition. Disruption of fdeC resulted in greater adhesion to CHIC-8E11 cells and increased motility at 42 °C compared to wild type (WT) and higher expression of multiple transporter proteins that increased inorganic ion export. Increased motility may be related to increased inorganic ion export since this resulted in downregulation of YbjN, a protein known to supress motility. Inactivation of fdeC in APEC strain IMT5155 resulted in a weaker immune response in chickens compared to WT in experimental infections. Our findings suggest that FdeC is upregulated in the host and contributes to interactions with the host by down-modulating motility during colonization. A thorough understanding of the regulation and function of FdeC could provide novel insights into E. coli pathogenesis.

Objective To improve health conditions among hypogonadal men ≥70 years of age using testosterone undecanoate (TU) injections, progressive strength training, and oral supplements of vitamin D, calcium, and protein.Methods This study is a 1-year follow-up of a double-blind RCT lasting 20 weeks, including 148 older men ≥70 years old with low testosterone levels and mobility problems. During 52 weeks, 4 groups received either testosterone therapy (TU) or progressive resistance training (Training), both (Combo), or no intervention (Controls). Physiotherapists supported the training groups until week 20, while these participants continued trained on their own during weeks 21 to 52. The main outcome measure was the 30-s chair stand test.Results The following numbers of participants completed the trial: 20 (Combo), 20 (Controls), 24 (TU), and 14 (Training). When examining 30-s chair stand test performance within each group at baseline, and at weeks 4, 20 and 52, only the Combo group improved (p = 0.001, Friedman Test). Compared to controls, only the Combo group experienced reduced fatigue and tiredness (p

Two water frog species: the pool frog Pelophylax lessonae (L) and the marsh frog P. ridibundus (R) occur sympatrically in Central Europe and form mixed populations (genetic systems) with their hybrid, the edible frog P. esculentus (E). The aim of the study was to assess the species composition of water frogs in urban and rural populations and compare our current findings with the results of previous studies. We surveyed the same sites that were investigated by Berger et al. in 1962–1970 (Poznań, urban landscape) and 1977–1997 (Dezydery Chłapowski Landscape Park, rural landscape). Because some ponds surveyed in the past were destroyed or dried-up, we also explored others located in the adjacent areas. We captured frogs during breeding seasons 2020 and 2021 and identified them by the nuclear marker gene SAI-1. We found three types of populations in the urban area: R-E, E-E and R-E-L and four in the rural area: R-E, L-E, E-E and R-E-L. Compared to the historical data, we found a drastic decrease in the frequency of P. lessonae in urban and rural landscapes: from 89.1% and 68% to 2.7% and 1.8%, respectively. At the same time, the frequency of P. ridibundus increased from 2.2% and 0.1% to 40% and 29.6%, respectively. A similar pattern was found for P. esculentus whose frequency increased from 8.7% and 31.9% to 57.3% and 68.6%, respectively. Additionally, we confirmed the presence of a cryptogenic Balkan water frog, P. kurtmuelleri, which was recently discovered in south-western Poland. The frequency of SAI-1 allele specific for this taxon reached 7.3%. The patterns found in both types of landscapes are in line with the current situation of both parental species in Europe. Such dynamic changes show the need for long-term monitoring of the population compositions of water frogs, what is crucial for their conservation management.

ABSTRACTEscherichia coli intestinal infection pathotypes are characterized by distinct adhesion patterns, including the recently described clumpy adhesion phenotype. Here, we identify and characterize the genetic factors contributing to the clumpy adhesion of E. coli strain 4972. In this strain, the transcriptome and proteome of adhered bacteria were found to be distinct from planktonic bacteria in the supernatant. A total of 622 genes in the transcriptome were differentially expressed in bacteria present in clumps relative to the planktonic bacteria. Seven genes targeted for disruption had variable distribution in different pathotypes and nonpathogenic E. coli, with the pilV and spnT genes being the least frequent or absent from most groups. Deletion (Δ) of five differentially expressed genes, flgH, ffp, pilV, spnT, and yggT, affected motility, adhesion, or antibiotic stress. ΔflgH exhibited 80% decrease and ΔyggT depicted 184% increase in adhesion, and upon complementation, adhesion was significantly reduced to 13%. ΔflgH lost motility and was regenerated when complemented, whereas Δffp had significantly increased motility, and reintroduction of the same gene reduced it to the wild-type level. The clumps produced by Δffp and ΔspnT were more resistant and protected the bacteria, with ΔspnT showing the best clump formation in terms of ampicillin stress protection. ΔyggT had the lowest tolerance to gentamicin, where the antibiotic stress completely eliminated the bacteria. Overall, we were able to investigate the influence of clump formation on cell surface adhesion and antimicrobial tolerance, with the contribution of several factors crucial to clump formation on susceptibility to the selected antibiotics.IMPORTANCEThe study explores a biofilm-like clumpy adhesion phenotype in Escherichia coli, along with various factors and implications for antibiotic susceptibility. The phenotype permitted the bacteria to survive the onslaught of high antibiotic concentrations. Profiles of the transcriptome and proteome allowed the differentiation between adhered bacteria in clumps and planktonic bacteria in the supernatant. The deletion mutants of genes differentially expressed between adhered and planktonic bacteria, i.e., flgH, ffp, pilV, spnT, and yggT, and respective complementations in trans cemented their roles in multiple capacities. ffp, an uncharacterized gene, is involved in motility and resistance to ampicillin in a clumpy state. The work also affirms for the first time the role of the yggT gene in adhesion and its involvement in susceptibility against another aminoglycoside antibiotic, i.e., gentamicin. Overall, the study contributes to the mechanisms of biofilm-like adhesion phenotype and understanding of the antimicrobial therapy failures and infections of E. coli.

Melanoma is a cancer with a high incidence rate that, despite the significant development of therapeutic options, still remains a major problem. The identification of biomarkers to select the right therapy for the right patient is one of the possibilities to improve the prognosis of patients. Potentially, the function of biomarkers could be played long non-coding RNAs (lncRNAs). The expression of selected 90 lncRNAs in serum from 30 metastatic melanoma patients with confirmed mutations in the BRAF V600 E or K gene was studied. Serum was collected prior to BRAF and MEK inhibitor therapy. The control group consisted of 16 healthy volunteers. A total of 41 lncRNAs were identified the expression of which differed statistically significantly between the patient group and the healthy volunteers. In addition, it was shown that the expression of HOXA3as (p = 0.033), PRINS (p = 0.036) and RNCR3 (p = 0.045) is higher in patients with the presence of CNS metastases, PFS inhibiting RNA (p = 0.048) is higher among patients with the presence of hepatic metastases, UCA1 (p = 0.008) expression is lower in patients with increased lactate dehydrogenase levels, while HOTAIRM1 (p = 0.044) and E2F4 antisense (p = 0.040) expression is lower in patients over 60 years of age. In addition, patients with high lincRNASFMBT2 expression showed longer median PFS (8.75 vs. 17.5 months, p = 0.0319) and OS (9.75 vs. 38 months (open observation, p = 0.0253). The obtained results require validation on a larger group of patients. If the results are confirmed, the indicated lncRNAs may play an important role as diagnostic and prognostic markers.

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer and the fifth cause of cancer-related deaths worldwide with a poor 5-year survival. SOX family genes play a role in the processes involved in cancer development such as epithelial–mesenchymal transition (EMT), the maintenance of cancer stem cells (CSCs) and the regulation of drug resistance. We analyzed the expression of SOX2-OT, SOX6, SOX8, SOX21, SOX30 and SRY genes in HNSCC patients using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, to assess their biological role and their potential utility as biomarkers. We demonstrated statistically significant differences in expression between normal and primary tumor tissues for SOX6, SOX8, SOX21 and SOX30 genes and pointed to SOX6 as the one that met the independent diagnostic markers criteria. SOX21 or SRY alone, or the panel of six SRY-related genes, could be used to estimate patient survival. SRY-related genes are positively correlated with immunological processes, as well as with keratinization and formation of the cornified envelope, and negatively correlated with DNA repair and response to stress. Moreover, except SRY, all analyzed genes were associated with a different tumor composition and immunological profiles. Based on validation results, the expression of SOX30 is higher in HPV(+) patients and is associated with patients’ survival. SRY-related transcription factors have vast importance in HNSCC biology. SOX30 seems to be a potential biomarker of HPV infection and could be used as a prognostic marker, but further research is required to fully understand the role of SOX family genes in HNSCC.

Abstract The gastric human pathogen Helicobacter pylori has developed mechanisms to combat stress factors, including reactive oxygen species (ROS). Here, we present a comprehensive study on the redox switch protein HP1021 regulon combining transcriptomic, proteomic and DNA-protein interactions analyses. Our results indicate that HP1021 modulates H. pylori’s response to oxidative stress. HP1021 controls the transcription of 497 genes, including 407 genes related to response to oxidative stress. 79 proteins are differently expressed in the HP1021 deletion mutant. HP1021 controls typical ROS response pathways (katA, rocF) and less canonical ones, particularly DNA uptake and central carbohydrate metabolism. HP1021 is a molecular regulator of competence in H. pylori, as HP1021-dependent repression of the comB DNA uptake genes is relieved under oxidative conditions, increasing natural competence. Furthermore, HP1021 controls glucose consumption by directly regulating the gluP transporter and has an important impact on maintaining the energetic balance in the cell.

Reproductive traits in dairy cattle are crucial for herd productivity and profitability. This study investigates the influence of relatedness to high immune response (HIR) Immunity+ sires on reproductive performance indicators in Polish Holstein-Friesian cows. A total of 5094 cows were analyzed, categorized based on their relatedness to HIR Immunity+ sires, and assessed for various reproductive parameters, including age at first insemination, gestation length, days open, calving interval, and calving ease. The results showed that the level of relatedness to HIR Immunity+ sires influenced certain reproductive traits, such as service period, gestation length, and age at first and second calving. Additionally, cows related to HIR Immunity+ sires exhibited a higher frequency of twin pregnancies and more complicated births. While some benefits were observed in certain reproductive traits among cows related to HIR Immunity+ sires, such as reduced age at first insemination and shortened gestation length, the overall impact on reproductive efficiency remains inconclusive. Further studies are needed to fully elucidate the effects of using semen from HIR Immunity+ sires on reproductive performance in dairy cattle.

Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Although the incidence is decreasing in developed countries, the treatment results are still unsatisfactory. The standard treatment for locally advanced gastric cancer (LAGC) is gastrectomy with perioperative chemotherapy. The association of selected microRNAs (miRNAs) with chemoresistance was assessed using archival material of patients with LAGC. Histological material was obtained from each patient via a biopsy performed during gastroscopy and then after surgery, which was preceded by four cycles of neoadjuvant chemotherapy (NAC) according to the FLOT or FLO regimen. The expression of selected miRNAs in the tissue material was assessed, including miRNA-21-3p, miRNA-21-5p, miRNA-106a-5p, miRNA-122-3p, miRNA-122-5p, miRNA-143-3p, miRNA-143-5p, miRNA-203a-3p, miRNA-203-5p, miRNA-551b-3p, miRNA-551b-5p, and miRNA-574-3p. miRNA expression was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The response to NAC was assessed using computed tomography of the abdomen and chest and histopathology after gastrectomy. The statistical analyses were performed using GraphPad Prism 9. The significance limit was set at p < 0.05. We showed that the expression of miR-143-3p, miR-143-5p, and miR-574-3p before surgery, and miR-143-5p and miR-574-3p after surgery, decreased in patients with GC. The expression of miR-143-3p, miR-143-5p, miR-203a-3p, and miR-551b-5p decreased in several patients who responded to NAC. The miRNA most commonly expressed in these cases was miRNA-551b-5p. Moreover, it showed expression in a patient whose response to chemotherapy was inconsistent between the histopathological results and computed tomography. The expression of miR-143-3p, miR-143-5p, miR-203a-3p, and miR-551b-5p in formalin-fixed paraffin-embedded tissue (FFPET) samples can help differentiate between the responders and non-responders to NAC in LAGC. miR-143-3p, miR-143-5p, and miR-574-3p expression may be used as a potential diagnostic tool in GC patients. The presence of miR-551b-5p may support the correct assessment of a response to NAC in GC via CT.

Melanoma is the most aggressive form of skin cancer. In the advanced stage of development, it is resistant to currently available therapeutic modalities. Increased invasiveness and metastatic potential depend on several proteins involved in various signal transduction pathways. Hippo signaling plays a vital role in malignant transformation. Dysfunctions of the Hippo pathway initiate the expression of tumor growth factors and are associated with tumor growth and metastasis formation. This review summarizes the recent achievements in studying the role of the Hippo pathway in melanoma pathogenesis and points to the potential specific targets for anti-melanoma therapy.

Abstract Background Infections caused by avian pathogenic Escherichia coli (APEC) result in significant economic losses in poultry industry. APEC strains are known to form biofilms in various conditions allowing them to thrive even under harsh and nutrient-deficient conditions on different surfaces, and this ability enables them to evade chemical and biological eradication methods. Despite knowing the whole genome sequences of various APEC isolates, little has been reported regarding their biofilm-associated genes. A random transposon mutant library of the wild-type APEC IMT 5155 comprising 1,300 mutants was analyzed for biofilm formation under nutrient deprived conditions using Videoscan technology coupled with fluorescence microscopy. Seven transposon mutants were found to have reproducibly and significantly altered biofilm formation and their mutated genes were identified by arbitrary PCR and DNA sequencing. The intact genes were acquired from the wild-type strain, cloned in pACYC177 plasmid and transformed into the respective altered biofilm forming transposon mutants, and the biofilm formation was checked in comparison to the wild type and mutant strains under the same conditions. Results In this study, we report seven genes i.e., nhaA, fdeC, yjhB, lysU, ecpR, AJB35136 and fdtA of APEC with significant contribution to biofilm formation. Reintroduction of AJB35136 and fdtA, reversed the altered phenotype proving that a significant role being played by these two O-antigen related genes in APEC biofilm formation. Presence of these seven genes across nonpathogenic E. coli and APEC genomes was also analyzed showing that they are more prevalent in the latter. Conclusions The study has elucidated the role of these genes in APEC biofilm formation and compared them to adhesion expanding the knowledge and understanding of the economically significant pathogens.

IntroductionMultidrug resistance in bacteria is a pressing concern, particularly among clinical isolates. Gram-negative bacteria like Salmonella employ various strategies, such as altering membrane properties, to resist treatment. Their two-membrane structure affects susceptibility to antibiotics, whereas specific proteins and the peptidoglycan layer maintain envelope integrity. Disruptions can compromise stability and resistance profile toward xenobiotics. In this study, we investigated the unexplored protein SanA’s role in modifying bacterial membranes, impacting antibiotic resistance, and intracellular replication within host cells.MethodsWe generated a sanA deletion mutant and complemented it in trans to assess its biological function. High-throughput phenotypic profiling with Biolog Phenotype microarrays was conducted using 240 xenobiotics. Membrane properties and permeability were analyzed via cytochrome c binding, hexadecane adhesion, nile red, and ethidium bromide uptake assays, respectively. For intracellular replication analysis, primary bone marrow macrophages served as a host cells model.ResultsOur findings demonstrated that the absence of sanA increased membrane permeability, hydrophilicity, and positive charge, resulting in enhanced resistance to certain antibiotics that target peptidoglycan synthesis. Furthermore, the sanA deletion mutant demonstrated enhanced replication rates within primary macrophages, highlighting its ability to evade the bactericidal effects of the immune system. Taking together, we provide valuable insights into a poorly known SanA protein, highlighting the complex interplay among bacterial genetics, membrane physiology, and antibiotic resistance, underscoring its significance in understanding Salmonella pathogenicity.

Automatic milking systems (AMSs) give cows relative freedom to choose the time and frequency of milking throughout the day. Feeding stations also may improve the management of farms. Combining milking robots and feeding stations (FS) may improve milking efficiency and milk yield. Therefore, combining AMS and FS may be beneficial for farmers. The objective of the research was to compare selected automatic milking parameters (daily indices per cow) registered by an AMS in relation to selected features including the presence of concentrate feeding stations. We analysed 931 cows born in 2013–14, in lactations 1–8. In total, we collected data from 357 318 milking days. The following parameters were examined: milking frequency (n/24 h), number of rejected milking (n/24 h), the average number of nipple attempts (n/milking), milking speed (kg/min), time spent in the milking box (s/24 h), milk yield (kg/24 h), milking efficiency (kg/min), rumination time (min/24 h), and concentrate intake (kg) per 100 kg of milk produced. The statistical analysis was conducted using a multi-factor analysis of variance. The analysis confirmed a statistical effect of the concentrate feeding system on most of the investigated traits, except for nipple attempts, box time and rumination time. In cows in barns with an FS, the following parameters were statistically higher compared to cows in non-FS barns: milking frequency (3.04 vs 2.73n/24 h), number of rejected milking (2.24 vs 1.51n/24 h), milking speed (2.98 vs 2.64 kg/min), milk yield (33.48 vs 30.14 kg/24 h), milking efficiency (1.80 vs 1.67 kg/min), and concentrate intake per 100 kg of milk produced (14.67 vs 12.67 kg). The study results indicate that using feeding stations in combination with an AMS can increase milking efficiency, hence the milk output from a milking robot.

Alopecia constitutes one of the most common dermatological disorders, and its steadily increasing prevalence is a cause for concern. Alopecia can be divided into two main categories, cicatricial/scarring and non-cicatricial/non-scarring, depending on the causes of hair loss and its patterns. The aim of this study was to investigate the relationship between anthropometric and nutritional laboratory parameters in Caucasian adult women and men with non-cicatricial alopecia. A total of 50 patients (37 with non-cicatricial alopecia and 13 healthy controls) were included in the study. Clinical examination and scalp trichoscopy were performed. The anthropometric and nutritional laboratory parameters were collected and analyzed. No statistically significant differences in the laboratory findings were found. The patients with non-cicatricial alopecia were statistically significantly younger as compared to the controls. An elevated risk of hair loss, which was detected among the younger participants, might be associated with a modern lifestyle and the so-called ‘Western diet’. It seems safe to assume that suboptimal nutrition and poor eating habits during childhood might constitute risk factors for early hair loss.

Head and neck squamous cell carcinoma (HNSCC) is one of the ten most common cancers. Most cancer cases originate from alcohol and tobacco consumption. However, studies have demonstrated that human papillomavirus (HPV) infection, particularly HPV-16, may also significantly influence disease progression. The KRAB-ZNF family of genes is involved in epigenetic suppression, and its involvement in carcinogenesis is the subject of extensive studies. The available literature data demonstrate that they may play different roles, both as tumor suppressors and oncogenes. In this study, six ZNF genes, ZFP28, ZNF132, ZNF418, ZNF426, ZNF540, and ZNF880, were tested using several in silico approaches based on the TCGA and GEO datasets. Our analyses indicate that the expression of the analyzed ZNFs was significantly downregulated in tumor tissues and depended on tumor localization. The expression levels of ZNFs differed between HPV-positive vs. HPV-negative patients depending on the clinical-pathological parameters. More specifically, the patients with higher levels of ZNF418 and ZNF540 showed better survival rates than those with a lower expression. In addition, the level of ZNF540 expression in HPV-positive (HPV(+)) patients was higher than in HPV-negative (HPV(−)) patients (p < 0.0001) and was associated with better overall survival (OS). In conclusion, we demonstrate that ZNF540 expression highly correlates with HPV infection, which renders ZNF540 a potential biomarker for HNSCC prognosis and treatment.

Among carbapenem-resistant Enterobacterales, metallo-beta-lactamase producing strains represent a growing therapeutic challenge. While the association of aztreonam and ceftazidime-avibactam has been investigated in recent years for the treatment of infections involving these strains, little to no clinical data support the use of this association for the treatment of bone and joint infections. We report two cases of complex bone and joint infections involving metallo-beta-lactamase-producing Enterobacterales, successfully treated at our referral center with aztreonam and ceftazidime-avibactam for 12 weeks in continuous infusions through elastomeric infusors.

Non-collinearly-seeded, KTA-based NOPCPA is used to generate multicolor, angularly separated pump pulses above 2 μm wavelength. These multicolor pump channels are used to amplify LWIR pulses in a non-collinearly-pumped ZGP NOPCPA to sub-mJ level, with potential scalability beyond 10 mJ. © 2024 The Authors.

One of the more interesting discoveries in neuroscience in recent years is the impact that the use of non-directive forms of communication, including stories and metaphors, has on our brain. In this article, we will review the most important literature of recent research in this area, and address both the benefits and risks of the new knowledge gained from these discoveries.

Here, the authors describe a patient with a pandrug-resistant Pseudomonas aeruginosa spinal abscess successfully treated with a personalized combination of phage therapy and antibiotics.

We present four cases of rare developmental anomalies in the smooth snake Coronella austriaca Laurenti, 1768 from western Poland. These include brachycephaly, lordosis, a supernumerary row of ‘ventral’ scales, and the third reported case of dicephalism in snakes from Poland. All the cases are supported by X-ray radiography. One of the possible explanations for these anomalies is a low genetic variation in populations from western Poland.

The objective of our study was to evaluate the predictive ability of a multi-trait genomic prediction model that accounts for interactions between marker effects to estimate heritability and genetic correlations of traits including 305-day milk yield, milk fat percentage, milk protein percentage, milk lactose percentage, and milk dry matter percentage in the Polish Holstein Friesian cow population. For this aim, 14,742 SNP genotype records for 586 Polish Holstein Friesian dairy cows from Poland were used. Single-Trait-ssGBLUP (ST) and Multi-Trait-ssGBLUP (MT) methods were used for estimation. We examined 305-day milk yield (MY, kg), milk fat percentage (MF, %), milk protein percentage (MP, %), milk lactose percentage (ML, %), and milk dry matter percentage (MDM, %). The results showed that the highest marker effect rank correlation was found between milk fat percentage and milk dry matter. The weakest marker effect rank correlation was found between ML and all other traits. Obtained accuracies of this study were between 0.770 and 0.882, and 0.773 and 0.876 for MT and ST, respectively, which were acceptable values. All estimated bias values were positive, which is proof of underestimation. The highest heritability value was obtained for MP (0.3029) and the lowest heritability value was calculated for ML (0.2171). Estimated heritability values were low for milk yield and milk composition as expected. The strongest genetic correlation was estimated between MDM and MF (0.4990) and the weakest genetic correlation was estimated between MY and ML (0.001). The genetic relations with milk yield were negative and can be ignored as they were not significant. In conclusion, multi-trait genomic prediction can be more beneficial than single-trait genomic prediction.

BackgroundThe main objective was to evaluate the efficacy of intranasal photodynamic therapy (PDT) in SARS-CoV-2 mildly symptomatic carriers on decreasing the infectivity period. SARS-CoV-2-specific immune-stimulating effects and safety were also analysed.MethodsWe performed a randomized, placebo-controlled, clinical trial in a tertiary hospital (NCT05184205). Patients with a positive SARS-CoV-2 PCR in the last 48 hours were recruited and aleatorily assigned to PDT or placebo. Patients with pneumonia were excluded. Participants and investigators were masked to group assignment. The primary outcome was the reduction in in vitro infectivity of nasopharyngeal samples at days 3 and 7. Additional outcomes included safety assessment and quantification of humoral and T-cell immune-responses.FindingsPatients were recruited between December 2021 and February 2022. Most were previously healthy adults vaccinated against COVID-19 and most carried Omicron variant. 38 patients were assigned to placebo and 37 to PDT. Intranasal PDT reduced infectivity at day 3 post-treatment when compared to placebo with a β-coefficient of -812.2 (CI95%= -478660 – -1.3, p34) at day 7 was higher on the PDT-group, with an OR of 0.15 (CI95%=0.04-0.58). There was a decay in anti-Spike titre and specific SARS-CoV-2 T cell immunity in the placebo group 10 and 20 weeks after infection, but not in the PDT-group. No serious adverse events were reported.InterpretationIntranasal-PDT is safe in pauci-symptomatic COVID-19 patients, it reduces SARS-CoV-2 infectivity and decelerates the decline SARS-CoV-2 specific immune-responses.

Enthusiasm for long-acting reversible contraception (LARC) is growing among donors and NGOs throughout the global reproductive health field. There is an emerging concern, however, that the push to insert these methods has not been accompanied by a commensurate push for access to method removal. We use data from 17 focus group discussions with women of reproductive age in an anonymized African setting to understand how users approach providers to request method removal, and how they understand whether or not such a request will be granted. Focus group participants described how providers took on a gatekeeping role to removal services, adjudicating which requests for LARC removal they deemed legitimate enough to be granted. Participants reported that providers often did not consider a simple desire to discontinue the method to be a good enough reason to remove LARC, nor the experience of painful side-effects. Respondents discussed the deployment of what we call legitimating practices, in which they marshalled social support, medical evidence, and other resources to convince providers that their request for removal was indeed serious enough to be honored. This analysis examines the starkly gendered nature of contraceptive coercion, in which women are expected to bear the brunt of contraceptive side-effects, while men are expected to tolerate no inconvenience at all, even vicarious. This evidence of contraceptive coercion and medical misogyny demonstrates the need to center contraceptive autonomy not only at the time of method provision, but at the time of desired discontinuation as well.

Abstract Background Immune involvement is well-described in Parkinson’s disease (PD), including an adaptive T lymphocyte response. Given the increasing prevalence of Parkinson’s disease in older age, age-related dysregulation of T lymphocytes may be relevant in this disorder, and we have previously observed changes in age-associated CD8+ T cell subsets in mid-stage PD. This study aimed to further characterise T cell immunosenescence in newly diagnosed PD patients, including shifts in CD4+ and CD8+ subpopulations, and changes in markers of cellular ageing in CD8+ T lymphocytes. Methods Peripheral blood mononuclear cells were extracted from the blood of 61 newly diagnosed PD patients and 63 age- and sex-matched controls. Flow cytometric analysis was used for immunophenotyping of CD8+ and CD4+ lymphocyte subsets, and analysis of recent thymic emigrant cells. Telomere length within CD8+ T lymphocytes was assessed, as well as the expression of the telomerase reverse transcriptase enzyme (hTERT), and the cell-ageing markers p16INK4a and p21CIP1/Waf1. Results The number of CD8+ TEMRA T cells was found to be significantly reduced in PD patients compared to controls. The expression of p16INK4a in CD8+ lymphocytes was also lower in patients versus controls. Chronic latent CMV infection was associated with increased senescent CD8+ lymphocytes in healthy controls, but this shift was less apparent in PD patients. Conclusions Taken together, our data demonstrate a reduction in CD8+ T cell replicative senescence which is present at the earliest stages of Parkinson’s disease.

Abstract Background The host-unrestricted, non-typhoidal Salmonella enterica serovar Enteritidis (S. Enteritidis) and the serovar Typhimurium (S. Typhimurium) are major causative agents of food-borne gastroenteritis, and the host-restricted Salmonella enterica serovar Gallinarum (S. Gallinarum) is responsible for fowl typhoid. Increasing drug resistance in Salmonella contributes to the reduction of effective therapeutic and/or preventive options. Bacteriophages appear to be promising antibacterial tools, able to combat infectious diseases caused by a wide range of Salmonella strains belonging to both host-unrestricted and host-restricted Salmonella serovars. Methods In this study, five novel lytic Salmonella phages, named UPWr_S1-5, were isolated and characterized, including host range determination by plaque formation, morphology visualization with transmission electron microscopy, and establishment of physiological parameters. Moreover, phage genomes were sequenced, annotated and analyzed, and their genomes were compared with reference Salmonella phages by use of average nucleotide identity, phylogeny, dot plot, single nucleotide variation and protein function analysis. Results It was found that UPWr_S1-5 phages belong to the genus Jerseyvirus within the Siphoviridae family. All UPWr_S phages were found to efficiently infect various Salmonella serovars. Host range determination revealed differences in host infection profiles and exhibited ability to infect Salmonella enterica serovars such as Enteritidis, Gallinarum, Senftenberg, Stanley and Chester. The lytic life cycle of UPWr_S phages was confirmed using the mitomycin C test assay. Genomic analysis revealed that genomes of UPWr_S phages are composed of 51 core and 19 accessory genes, with 33 of all predicted genes having assigned functions. UPWr_S genome organization comparison revealed 3 kinds of genomes and mosaic structure. UPWr_S phages showed very high sequence similarity to each other, with more than 95% average nucleotide identity. Conclusions Five novel UPWr_S1-5 bacteriophages were isolated and characterized. They exhibit host lysis range within 5 different serovars and are efficient in lysis of both host-unrestricted and host-restricted Salmonella serovars. Therefore, because of their ability to infect various Salmonella serovars and lytic life cycle, UPWr_S1-5 phages can be considered as useful tools in biological control of salmonellosis.

IntroductionIn neonatal intensive care units (NICUs), the standard chemical-based disinfection procedures do not allow a complete eradication of pathogens from environmental surfaces. In particular, the clone Staphylococcus capitis NRCS-A, a significant pathogen in neonates, was shown to colonize neonatal incubators. The aim of this study was to evaluate the in vitro effect of a bacteriophage cocktail on NRCS-A eradication.MethodsThree bacteriophages were isolated, genetically characterized and assessed for their host range using a collection of representative clinical strains (n=31) belonging to the clone NRCS-A. The efficacy of a cocktail including these three bacteriophages to eradicate the reference strain S. capitis NRCS-A CR01 was determined in comparison or in combination with the chemical disinfectant Surfanios Premium on either dry inoculum or biofilm-embedded bacteria. The emergence of bacterial resistance against the bacteriophages alone or in cocktail was evaluated by growth kinetics.ResultsThe three bacteriophages belonged to two families and genera, namely Herelleviridae/Kayvirus for V1SC01 and V1SC04 and Rountreeviridae/Andhravirus for V1SC05. They were active against 17, 25 and 16 of the 31 tested strains respectively. Bacteriophage cocktails decreased the bacterial inoculum of both dry spots and biofilms, with a dose dependent effect. The sequential treatment with bacteriophages then Surfanios Premium did not show enhanced efficacy. No bacterial resistance was observed when using the bacteriophage cocktail.DiscussionThis study established a proof-of-concept for the use of bacteriophages to fight against S. capitis NRCS-A. Further investigations are needed using a larger bacterial collection and in real-life conditions before being able to use such technology in NICUs