Analysis of efficacy and safety of vismodegib therapy in patients with advanced basal cell carcinoma - real world multicenter cohort study.

BACKGROUND: Basal cell carcinoma (BCC) is the most frequent non-melanoma skin cancer. The basis of treatment is surgical resection. The treatment of locally advanced and metastatic disease is currently based on sonidegb or vismodegib, small molecule inhibitors of the hedgehog signalling pathway. OBJECTIVES: The study aimed to retrospectively analyse the efficacy and safety of treatment with vismodegib in 108 patients with locally advanced or metastatic disease treated from August 1st, 2017 to December 31st, 2020. The primary objective was to evaluate the objective response rate (ORR), overall survival (OS) and progression-free survival rates. The secondary aims of the study were the disease control rate, the incidence of adverse events (AEs) and the estimation of the factors that potentially impact the treatment outcome and patient survival. METHODS: Patients treated in national drug programme were enrolled into this retrospective cohort study. Evaluation of the treatment efficacy was performed according to CT/MRI scans and by the response evaluation criteria in solid tumours (RECIST) 1.1. The safety evaluation was performed according to the Common Terminology Criteria for Adverse Events v. 5.0 (CTCAE) classification and severity assessment. RESULTS: The median duration of treatment was 14 months (range 1-94 months). The median progression-free survival reached 30.5 months (95% CI; 24.8-36.3), and the progression-free survival rate after 6, 12 and 24-months were 92%, 78% and 61%, respectively. The median overall survival was 41.5 months (95% CI; 31.6-51.3), and the overall survival rate after 1, 2 and 3 years accordingly 86%, 73% and 60%. The univariant and multivariant analysis indicated that the female gender is an independent positive prognostic factor of progression-free survival. CONCLUSIONS: The response to treatment is the prognostic factor for response maintenance and better overall survival. The therapy was well tolerated with the safety profile consistent in general with known from previous studies.

Secondary sexual traits and semen characteristic of chicken germline chimeras.

Birds obtained by embryo engineering are used to study embryo development and to produce transgenic birds. As this method of producing birds still generate strong emotions of the public opinion head ornaments, testes and semen characteristics of sex chimera roosters were examined to check whether they differ from chickens obtained by non-manipulated methods. Measurements of head ornaments, testes and semen were correlated with each other. Semen quality factor (SQF) was calculated, as well as the level of fluctuating asymmetry (FA) of bilateral traits (wattles and testes). Positive correlation was found for comb width and wattle length and comb thickness and sperm concentration. Semen characteristics and FA did not exceed the level encounter in other chicken lines. Results obtained indicate that germline chimeras are similar in appearance of secondary sexual traits, and semen and testes characteristics to chickens produced in non-manipulated way.

The sonographic morphology of musculus palmaris longus in humans.

BACKGROUND: The aim of this work was to describe morphology and morphometry of musculus palmaris longus and compare the outcome of Shaeffer's test with ultrasound imaging. MATERIALS AND METHODS: Forty forearms of 20 healthy volunteers (11 females, 9 males) were tested by Shaeffer's test and ultrasound imaging. Anthropological measurements of the forearm and ultrasound guided measurements of musculus palmaris longus were taken. The outcome was tested for statistical significance by Fisher's test. RESULTS: The examination revealed agenesis of palmaris longus in 6 cases, as well as 6 muscles showing quality variations. The Shaeffer's test gave 4 false-negative results. 28 muscles were described as spindle-shaped and 8 as pennated or bipennated. However, all the spindle-shaped muscles demonstrated a tendon going inside of the muscle's belly ranging from 2 cm to 11.5 cm. The relation between the circumference of the forearm right below the elbow (mean: 15.38 cm, SD: 1.83 cm) and the approximated volume of the palmaris longus muscle's belly (mean: 4.72 cm3, SD: 1.57 cm3) proved to be statistically significant (Fisher's test p-value < 0.05). CONCLUSIONS: Uncommon morphological variations have been shown. Spindle-shaped muscles have proved to have their tendons continued inside them. Palmaris longus muscle's belly has proved to take significant amount of volume within the proximal forearm. Shaeffer's test has shown to have 10% false-negative ratio.

Effect of selenium and vitamin E addition to the extender on liquid stored capercaillie (Tetrao urogallus) semen quality.

Captive breeding has become an important tool in species conservations programmes, maintaining genetic diversity and restoring wild, endangered populations. In order to improve the reproductive efficiency of captive kept capercaillie, the purpose of the study was to determine the effect of selenium and vitamin E addition to semen extender on sperm characteristic during short-term storage. Ejaculates collected individually from four capercaillie were divided into two parts, diluted threefold with basic EK extender and EK enriched with 1 mg/ml of organic selenium and 8 mg/ml of vitamin E (EK+Se+E) and stored 24 hr at temp. +4°C. Spermatozoa morphology, motility and motility parameter were evaluated in net, diluted and stored semen samples. Significant (p < .05) differences between individual males were stated in relation to the majority of traits evaluated in the freshly collected semen. Comparing to the fresh semen, a significant (p < .05) decrease in percentage of live sperm in total (by 3.8% points on average) has been observed in samples diluted by EK extender, while in semen diluted with EK+Se+E extender this decrease was lower (1.5%pts on average) and not significant. Also per cent of motile sperm in EK+Se+E extender was higher (p < .05) then in EK (71.6% vs. 58.9%), but taking into account the values of individual males, both extender and male effect on liquid semen storage become apparent. Obtained data allow concluding that selenium and vitamin E addition to EK extender had positive effect on morphology and motility of capercaillie semen stored 24 hr at 4°C and can be recommended for similar studies carried out on other Galliformes species.

Development of cross-priming amplification for direct detection of the African Swine Fever Virus, in pig and wild boar blood and sera samples.

UNLABELLED: African swine fever (ASF) is considered a major threat to the production of pigs worldwide. The ASF aetiological agent, ASFV, is the sole member of the Asfivirus genus, belonging to the Asfarviridae family. An effective ASF vaccine is not currently available, thus the only measures of ASF spread control include, reliable and fast diagnosis. Officially approved, diagnostic methods include, virus isolation, serological assays, including enzyme-linked immunosorbent assay and immunoperoxidase assay (IPT) and different modifications of the polymerase chain reaction (PCR). This paper describes the first development and application of a cross-priming amplification method (CPA) for the direct detection of genetic ASFV material, in blood and sera from pigs and wild boars. This method is specific only to ASFV DNA. The study showed that CPA had equal sensitivity, in comparison to the official, universal probe library (UPL) real-time PCR and reached 7·2 copies of standard plasmid DNA, containing a p72 gene fragment. This method was capable of detecting ASFV DNA in all examined blood samples, originating from pigs; n = 10 and wild boars; n = 76. The obtained results were also confirmed by the officially approved, real-time PCR. The developed CPA might be further used by local and county veterinary officers, hunters or pig farmers, for preliminary ASF diagnosis. SIGNIFICANCE AND IMPACT OF THE STUDY: The spread of the African swine fever virus (ASFV) among infected pigs and wild boars, is currently one of the most important facets of virus transmission in eastern Europe. Cross-priming amplification (CPA) has been developed, for fast and direct development of genetic ASFV material in the blood and sera of infected pigs and wild boars. It has been shown that CPA is a rapid, sensitive and specific isothermal method for the detection of ASFV DNA, in directly collected blood or sera from pigs and wild boars.

Usage of Over-the-Counter and Herbal Products in Common Cold in Poland: Findings from Consumer Survey.

Upper respiratory tract infections are usually self-treated with synthetic and herbal over-the-counter products. The aim of the study was to assess the reasons for the purchase of those medications in Poland. We examined 413 adults, aged 18 and over (70.5% of them were women) using a questionnaire. The findings demonstrate that oral synthetic products were used by 76% of respondents, while herbal products by 30%. Synthetic products were used mainly by educated people under 65 years of age, students, and the employed. Herbal products were used mainly by older people. In conclusion, synthetic products against common cold are perceived as more effective. Such medications are used by people who probably would like to recover and return to professional activity as quickly as possible. As they generally use more medications, they are at increased risk of adverse effects resulting from drug interactions, and they should be a target group for health education programs.

The Usefulness of Captive Kept Capercaillie (Tetrao urogallus L.) as the Semen Donors for Artificial Insemination and Gene Pool Preservation In vitro.

Captive breeding of birds threatened by extinction in zoological gardens or other closed aviary centres is one of the methods allowing their protection and gene pool preservation ex situ in vivo. Such birds are usually kept in captivity lifelong and serve as parents of several new generations that can be further released into natural environment, or males are used as semen donors for artificial insemination and gene banking. Therefore, the fecundity of such flocks (number of laid egg and spermatozoa quantity and quality) is very important. The aim of this study was to evaluate the usefulness of captive kept capercaillie (Tetrao urogallus L.) as semen donors in three subsequent reproductive seasons, based on the assessment of manually collected semen quality. Male response to dorso-abdominal massage, ejaculate volume, sperm concentration, motility and morphology were evaluated individually at three succeeding years. Depending on individual male properties and year of collection, the number of positive reactions to semen collection attempts (i.e. ending with ejaculation) varied from 44.4% to 100.0%; single ejaculate volume ranged from 10 to 300 µl, spermatozoa concentration from 10 × 10(6) per ml to 3520 × 10(6) per ml and percentage of live morphologically normal spermatozoa from 19.3 to 80.3%. The highest average value (66.7) of semen quality factor (SQF) was noted for a 2-year-old male (varying from 1.9 to 258.1), while the lowest for ten- (4.8; varying from 0.1 to 17.0) and 7-year-old (6.6; varying between 0.6 and 13.6). Assuming that for AI purposes, the ejaculate quality has to be at minimum 10 SQF, obtained results indicate that majority of capercaillie kept in captivity, both young (2-3 years old) and older (up to 10 years old), can be valuable semen producers in succeeding seasons.

High order kinoforms as a broadband achromatic diffractive optics for terahertz beams.

We discuss thin optical structures that allow chromatic aberrations to be avoided in the THz domain. The paper contains the theoretical considerations, computer modeling and experimental evaluation of the high order kinoform diffractive elements in the THz range. According to the obtained results application of the high order kinoforms enables broadband operation in the THz range.

A fully capable pianist with a congenital bilateral agenesis of extensor pollicis brevis muscle.

A 28-year-old male musical student has been presented with visible inability of active abduction and extension of the thumbs in both hands beyond the neutral position. The student has not been previously diagnosed and claimed no history of trauma or surgical procedures in the area of hands and no family history of such disabilities. The student remained capable of playing on keyboard instruments on high level due to compensation by hyperextension of the interphalangeal joint of both thumbs and showed no increased frequency of the injuries or playing-related disorders. The ultrasound and magnetic resonance imaging showed complete bilateral agenesis of extensor pollicis brevis muscles and was classified as isolated congenital clasped thumb syndrome. Due to the age of the student and the agenesis of the muscles the conservative treatment was deemed inadequate and due to high functionality of the student as a musician and unforeseeable results it might have on a musician's career, surgical treatment has been disadvised.

Peer assessment as a method for measuring harmful internet use.

Harmful Internet use (HIU) describes unintended use of the Internet. It could be both self-harm and harming others. Our research goal is to develop a more accurate method for measuring HIU by this novel peer assessment. As such, it may become, with our call for more research, a paradigm shift supplementing every rating scale or other type of Internet use assessment. In addition to classic statistical analysis, structural equations have been employed. Results indicate that the true positive rate (TPR) is substantially higher than assessed in other studies.•Peer assessment improvement.•AUC for ROC was computed to establish cut-off points for the used scale.•Results obtained by the Structural Equation model indicate that parental care has a moderate influence on subjects' attempts to fight HIU.

Effects of sex and inclusion of dried distillers grains with solubles on slaughter yield and meat characteristics of Pekin ducks.

1. The effects of dried distillers grains with solubles (DDGS) dietary inclusion concentration, and sex, on body weight, slaughter efficiency and meat characteristics of Pekin ducks (Anas platyrhynchos f. domestica, strain P55) were studied. 2. Sexed ducklings (n = 160) were divided randomly into 4 groups (each with 4 replicates). From d 1 to d 21, all the birds received the same commercial feed, then from 22 to 49 d of age the ducks were fed in the following groups: control (commercial feed) and three experimental groups (15%, 25% and 30% inclusion of DDGS). All ducks were weighed individually at d 1, 21 and 49. On the day of slaughter, 5 males and 5 females, of body weight close to the average weight for group and sex, were selected from each group, slaughtered and the following parameters were evaluated: slaughter yield, weight, and percentage of particular elements of carcase, physical and chemical characteristics of meat. 3. The results obtained showed that DDGS included from 22 to 49 d of rearing, at concentrations up to 30%, in a commercial Pekin duck diet did not affect the live body weight, slaughter yield, weight, and percentage of breast and leg muscle, skin with subcutaneous fat, and abdominal fat. There were no differences in physical characteristics (pH(15), pH(24,) meat colour values L*, a*and b*, and hygroscopicity) of breast muscle, as well as in cholesterol content. DDGS addition at 30% significantly increased fat content in male, and crude protein in female, breast meat. Sex effect was observed only in a few traits and was diet dependent. Final body weight of females fed 30% DDGS was significantly lower than males; in the control and 15% DDGS group females had higher percentage of skin with subcutaneous fat. 4. The results obtained, and relative costs of feeds produced, allows the recommendation of DDGS addition at up to 30% to commercial Pekin duck diets from 22 d of age.

Morphology of sesamoid bones in keyboard musicians.

BACKGROUND: The sesamoid bones are small, usually oval bone structures often found in joints and under the tendons. Although their precise function is not fully understood, it is agreed upon that they protect the joints and make movements faster and less energy consuming. Sesamoid bones are found in hands, especially around first, second and fifth metacarpophalangeal joint and the interphalangeal joint of the thumb. MATERIALS AND METHODS: This study compares a group of 32 young musicians to 30 non-musicians of similar age and posture. The hands of the subjects were examined by ultrasound imaging for the presence of sesamoid bones. The results were noted and observed sesamoids were measured. RESULTS: The results seem to prove that although there are no difference in the amount or the location of the sesamoid bones between the musicians and the non-musicians, there is statistically significant tendency for the musicians to have bigger sum of the sesamoid's volume per hand (Fisher's test p-value = 0.034 < 0.05). CONCLUSIONS: There was also observed an unusually shaped "Bactrian" sesamoid bone at the interphalangeal joint of the thumb in 8 cases in the musicians' group and 1 case in the control group. All participants with the aforementioned structure were female.

IL-23 in the pathogenesis of rheumatoid arthritis.

Interleukin-23 (IL-23) is a heterodimeric cytokine belonging to the IL-6/IL-12 family that plays a key role in several of autoimmune and inflammatory disorders. This family contains the 34 type I cytokine receptor chains and 27 ligands, which share structural and functional similarities, but on the other hand they display distinct roles in shaping Th cells responses. IL-12 family cytokines have not only proinflammatory effects but they also promote inflammatory responses. IL-23 is composed of the p40 subunit in common with IL-12, and with a unique p19 subunit. IL-23 binding to an IL-23 receptor expressed on dendritic cells, macrophages and monocytes triggers the activation of Jak2 and Tyk2, which in turn phosphorylates STAT1, STAT3, STAT4 and STAT5 as well as induce formation of STAT3-STAT4 heterodimers. IL-23 is one of the essential factors required for the survival and/or expansion of Th17 cells, which produce IL-17, IL-17F, IL-6 and TNF-alpha. Th17 cells stimulated by the IL-23 promote osteoclastogenesis through production of IL-17, which induce receptor activator of NF-kappa B ligand on mesenchymal cells. The IL-23-IL-17 axis includes Th17 cells and plays a key role in the development of autoimmune arthritis.

Phylogenetic analysis of swine influenza viruses isolated in Poland.

Swine influenza virus (SIV) of H1N1 and H3N2 subtypes are dominated in European pigs population. "Classical swine" H1N1 subtype was replaced by "avian-like" H1N1 subtype. It co-circulates with H3N2 reassortant possessing "avian" genes. In the present study, 41 SIV strains isolated from pigs with pneumonia, raised in 20 Polish farms, were identified and characterised. Since it was evidenced that isolates from the same geographic district and the same year of isolation are in 100% similar, 15 strains representing different district and different year of isolation were chosen to construct phylogenetic trees. Two genes, conservative matrix 1 (M1) and the most variable, haemagglutynin (HA), were sequenced and subjected into phylogenetic analysis. The results of the analysis confirmed that "avian-like" swine H1N1 strains evolved faster than classical SIV strains. HA gene of these isolates have been derived from contemporary strains of "avian-like" SIV. In contrast, the M1 gene segment may have originated from avian influenza viruses. H3N2 strain is located in swine cluster, in the main prevalent European group of H3N2 isolates called A/Port Chalmers/1/73-like Eurasian swine H3N2 lineage, which has evolved separately from the human H3N2 virus lineage around 1973.

Phylogenetic evolution of swine-origin human influenza virus: a pandemic H1N1 2009.

The knowledge of the genome constellation in pandemic influenza A virus H1N1 2009 from different countries and different hosts is valuable for monitoring and understanding of the evolution and migration of these strains. The complete genome sequences of selected worldwide distributed influenza A viruses are publicly available and there have been few longitudinal genome studies of human, avian and swine influenza A viruses. All possible to download SIV sequences of influenza A viruses available at GISAID Platform (Global Initiative on Sharing Avian Influenza Data) were analyzed firstly through the web servers of the Influenza Virus Resource in NCBI. Phylogenetic study of circulating human pandemic H1N1 virus indicated that the new variant possesses a distinctive evolutionary trait. There is no one way the pandemic H1N1 have acquired new genes from other distinguishable viruses circulating recently in local human, pig or domestic poultry populations from various geographic regions. The extensive genetic diversity among whole segments present in pandemic H1N1 genome suggests that multiple introduction of virus have taken place during the period 1999-2009. The initial interspecies transmission could have occurred in the long-range past and after it the reassortants steps lead to three lineages: classical SIV prevalent in the North America, avian-like SIV in Europe and avian-like related SIV in Asia. This analysis contributes to the evidence that pigs are not the only hosts playing the role of "mixing vessel", as it was suggested for many years.

Genotype-dependent development of cellular and humoral immunity in the spleen and cecal tonsils of chickens stimulated in ovo with bioactive compounds.

Prebiotics, probiotics, and synbiotics, delivered in ovo influence the colonization and development of the peripheral immune system in poultry. This study aimed to investigate the influence of the host genotype (broiler chickens [Ross 308] and old native Polish breed Green-legged Partridgelike [GP] chickens) on the number of B and T cells in the spleen and cecal tonsils (CT). The solution of a bioactive compound was injected in ovo on day 12 of egg incubation: prebiotics (galactooligosaccharides [GOS]), probiotics (Lactococcus lactis subsp. cremoris IBB477), and synbiotics (GOS + L. lactis). The samples were collected on day 7, day 21, and day 42 after hatching (n = 8). The number of Bu-1+ (B) cells, CD4+ cells, and CD8+ cells in the spleen and CT was estimated using immunohistochemistry. The number of germinal centers (GC) was determined in the spleen. In broilers, probiotics increased (P < 0.05) the number of CD4+ cells in the CT on day 7. On day 21, prebiotics raised (P < 0.01) the number of cells involved in cellular immunity in the CT (CD4+ and CD8+ cells) and spleen (CD8+ cells). On day 42, it was synbiotics that stimulated the colonization of both the CT and spleen by B cells, but colonization of the spleen only by CD4+ and CD8+ cells. In GP chickens, synbiotics enforced the cellular immunity (CD4+ or CD8+ cells) in the spleen at all time points. Synbiotics also stimulated the GC appearance on day 21 and day 42. In GP chickens, the influence of bioactive compounds on colonization of the CT was very limited. In broilers, we determined pronounced and age-dependent effects of prebiotics and synbiotics on the number of B and T cells in both the CT and spleen. In GP chickens, the most potent compound was synbiotics, which stimulated cellular immunity in the spleen but not in the CT. However, given the long-term effects on adaptive immune cells, synbiotics were the most potent compounds in both chicken genotypes.

The amino-terminal domain of desmoplakin binds to plakoglobin and clusters desmosomal cadherin-plakoglobin complexes.

The desmosome is a highly organized plasma membrane domain that couples intermediate filaments to the plasma membrane at regions of cell-cell adhesion. Desmosomes contain two classes of cadherins, desmogleins, and desmocollins, that bind to the cytoplasmic protein plakoglobin. Desmoplakin is a desmosomal component that plays a critical role in linking intermediate filament networks to the desmosomal plaque, and the amino-terminal domain of desmoplakin targets desmoplakin to the desmosome. However, the desmosomal protein(s) that bind the amino-terminal domain of desmoplakin have not been identified. To determine if the desmosomal cadherins and plakoglobin interact with the amino-terminal domain of desmoplakin, these proteins were co-expressed in L-cell fibroblasts, cells that do not normally express desmosomal components. When expressed in L-cells, the desmosomal cadherins and plakoglobin exhibited a diffuse distribution. However, in the presence of an amino-terminal desmoplakin polypeptide (DP-NTP), the desmosomal cadherins and plakoglobin were observed in punctate clusters that also contained DP-NTP. In addition, plakoglobin and DP-NTP were recruited to cell-cell interfaces in L-cells co-expressing a chimeric cadherin with the E-cadherin extracellular domain and the desmoglein-1 cytoplasmic domain, and these cells formed structures that were ultrastructurally similar to the outer plaque of the desmosome. In transient expression experiments in COS cells, the recruitment of DP-NTP to cell borders by the chimera required co-expression of plakoglobin. Plakoglobin and DP-NTP co-immunoprecipitated when extracted from L-cells, and yeast two hybrid analysis indicated that DP-NTP binds directly to plakoglobin but not Dsg1. These results identify a role for desmoplakin in organizing the desmosomal cadherin-plakoglobin complex and provide new insights into the hierarchy of protein interactions that occur in the desmosomal plaque.

Stage of goose embryo development at oviposition depending on genotype, flock age, and period of laying.

Embryo development and chick quality are influenced by parental genotype, age, nutrition, environment, and flock management. The aim of study was to determine if genotype, age of goose or eggs laid near the onset of egg production vs. eggs laid near the end of reproduction influence the stage of embryo at oviposition. Three experiments were undertaken. To compare genotypes (Experiment 1) 150 eggs were collected from 3-year-old commercial line White Koluda (WK) geese and from two breeds involved in a genetic resources conservation program, Zatorska (Za) and Bilgoraj (Bi). Age comparison (Experiment 2) was conducted with 200 eggs collected from 1-, 2-, 3-, and 4-year-old WK geese. To compare laying periods (Experiment 3), 150 WK eggs were collected at the first week of March and 100 at the second half of June. Eggs were stored for 72 h at 16°C, staged using Eyal-Giladi and Kochav (EGK, Roman numerals) and Hamburger and Hamilton (HH, Arabic numerals) procedures. Experiment 1: Individual breed differences were evident with Stage X EGK embryos comprising 42.4, 33.3, and 38.7% in the eggs examined from the WK, Bi, and Za, respectively. For all breeds combined, 38.8% of the embryos were in Stage X, but in the next order in WK there was stage XI (18.2%), while in geese from the genetic reserve it was stage XIII (Bi - 33.3; Za - 29.0%). Experiment 2: In eggs of 1-, 2-, and 3-year-old WK geese, the majority of embryos (38.7, 32.4 and 42.2%, respectively) were in Stage X. In contrast, in 4-year-old geese the embryos were in Stage XI (36.1%). Experiment 3: In eggs collected in March and in June most of embryos were in Stage X (33.7% and 43.6%, respectively). In addition, more developmentally advanced stages (XI-XIII) were similar in both periods. However, embryos in Stage 2 HH were only observed in eggs collected at the end of laying season. Interestingly, earlier stages (VI-IX) were observed exclusively in the eggs collected in March.