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Podstawową zasadą leczenia choroby otyłościowej jest leczenie kompleksowe. Cele terapii powinny być indywidualnie dobierane do pacjenta i zależeć przede wszystkim od chorób współistniejących oraz ewentualnie występujących powikłań. Analogicznie do innych chorób przewlekłych, m.in.: nadciśnienia tętniczego, cukrzycy typu 2, przewlekłych zespołów wieńcowych, strategia leczenia choroby otyłościowej powinna obejmować metody niefarmakologiczne, farmakoterapię oraz, w razie braku skuteczności, leczenie operacyjne. Rekomendowany czas trwania farmakoterapii wynosi min. 12 miesięcy. Liraglutyd działa centralnie na neurony proopiomelanokortyny (POMC)/CART, zwiększając uczucie sytości oraz zmniejszając głód, z przejściowym efektem zmniejszającym opróżnianie żołądka, dzięki czemu kontroluje łaknienie. Spośród wielu korzystnych cech liraglutydu do udokumentowanych i szczególnie ważnych z klinicznego punktu widzenia zalicza się: pozytywny wpływ na zaburzenia gospodarki węglowodanowej, działanie kardioprotekcyjne na zmniejszenie ryzyka zgonu z przyczyn sercowo-naczyniowych, zawału lub udaru niezakończonego zgonem oraz zmniejszenie ciśnienia skurczowego u osób z nieprawidłową glikemią bądź bez niej w stosunku do placebo.

Swine is a common model organism for biomedical research. Epigenetic reprogramming in SCNT embryos does not fully recapitulate the natural DNA demethylation events at fertilisation. This study aimed to conduct a genome-wide methylation profiling to detect differentially methylated regions (DMRs) responsible for epigenetic differences in stem cells that displayed high and low efficiency of SCNT and to elucidate the low efficiency of cloning rate in pigs. Adipose tissue mesenchymal stem cells (AMSC)s lines were isolated from adipose tissue of adult male pigs (n=20; high-efficiency cells=10; low efficiency cells= 10). Reduced representation bisulfite sequencing (RRBS) was performed on an Illumina HiSeq1500. Paired-end reads were filtered to remove the adapter contamination, and low-quality reads using TrimGalore!. Filtered reads were mapped to the reference genome using Bismark. MethylKit was used to identify differentially methylated regions (DMRs) (bases and tiles), showing statistically significant differential methylation between two groups: high and low-efficiency AMSCs. Hierarchical cluster analysis according to methylation patterns clearly defined groups with low and high cloning efficiency. We report 3704 bases with statistically significant differences in methylation and 10062 tiles with statistically significant differences in methylation. Most differentially methylated sites are intergenic 62%, 31% are intronic, 4% are located in exons and 4% in promoters. 37% of differentially methylated sites are located in known CpG islands (CGIs) and 4% in CpG island shores (CGSs).

Background: Resistin action links to conditions such as diabetes, obesity, but its role in hypertension is less well understood. This study aimed to estimate the relationship between resistin (−420G/C) single nucleotide variant (SNV) and markers associated with endothelial dysfunction in hypertension. Methods: The study enrolled 162 hypertensive patients (HT) and 165 non-hypertensive (NHT) patients. Resistin serum concentration was estimated with immuoenzymatic assay. Anthropometric measurements, blood pressure and arterial stiffness index (SI), uric acid (UA) serum concentration, and salty taste preference of normal (NS) or high (HS) were assessed in the study. Genotyping was achieved by polymerase chain reaction-restriction fragment length polymorphism. Results: Resistin concentration and SI do not differ significantly between HT and NHT individuals; UA significantly increased in HT subjects. Resistin, UA, and SI did not differ among particular resistin genotypes in HT, NHT, NS, or HS groups. GG and CG genotypes were more frequent (OR 1.57 (95% CI; 1.01–2.43); p = 0.04) in hypertensive individuals than the NHT group, but less frequent (OR 0.58 (95% CI; 0.37–0.91); p = 0.01) in HS patients compared to NS individuals. Concerning HT patients with different salt preferences, GG + CG genotypes were less frequent (OR 0.50 (95% CI; 0.26–0.97); p = 0.04) in the HS group than in NS individuals. HT carriers of GG and CG genotype have significantly increased UA concentrations compared to the respective NHT subjects. HS individuals carrying GG and CG genotypes have higher SI values than the NS group. Allele G of SNV (−420G/C) adjusted for age, BMI, serum resistin, UA concentration, salt taste preference, SI, and HR values increased the risk of developing hypertensive phenotype 1.8 fold. Conclusions: Resistin SNV (−420G/C) is related to several markers associated with endothelial dysfunction, including salt taste preference in hypertensive patients.

The aim of this study was to identify candidate genes that could be useful predictors of better detection performance in drugs and explosives detection dogs. Single nucleotide polymorphisms in selected canine olfactory receptor genes responsible for olfactory acuity (OR1P2-like, OR51H5-like, OR52N9-like,OR52P3-like, OR9S13-like), and genes related to the serotoninergic (SLC6A4-like, HTR1A, HTR2B-like) and dopaminergic (SLC6A3-like, DRD1-like, DRD2-like) neurotransmission with a documented role in operant conditioning, were analysed. From a total of 91 certified drug and 57 explosives detection dogs, 10 individuals demonstrating the best and 10 with the poorest detection performance, as evaluated by detection speed and style of searching, were chosen for genetic studies. In this work for the first time we show that not only polymorphisms in selected canine olfactory receptor genes, but also polymorphisms in genes encoding the transporter protein for dopamine uptake or the 5-HT2B receptor, are important for canine olfactory detection. The G allele at the OR52N9-like:c.176 A > G and OR52N9-like:c.288 T > G loci had a negative, whereas the A allele at the OR9S13-like:c.592 G > A locus had a positive, effect on the dogs' detection performance measured as mean search time and mean search style. Additionally, the presence of the C allele in the SLC6A3-like:c.181 G > C locus and the A allele in HTR2B-like:c.596 G > A locus was associated with reduced detection performance. We suggest that good candidate dogs for detection training could be chosen for military and civilian service based on favourable genotypes in the olfactory and monoamine neurotransmitter receptor genes. This, however, should be investigated further in studies, particularly using dogs with the alleles of the candidate genes we have identified as correlated with increased performance.

Atg8 family proteins are highly-conserved eukaryotic proteins with diverse autophagy and non-autophagic functions in eukaryotes. While the structural features required for conserved autophagy functions of Atg8 are well-established, little is known about the molecular changes that facilitated acquisition of divergent, non-autophagic functions of Atg8. The malaria parasite Plasmodium falciparum offers a unique opportunity to study non-autophagic functions of Atg8 family proteins because it encodes a single Atg8 homolog whose only essential function is in the inheritance of an unusual secondary plastid called the apicoplast. Here we used functional complementation to investigate the structure-function relationship for this divergent Atg8 protein. We showed that the LC3-interacting region (LIR) docking site (LDS), the major interaction interface of Atg8 protein family, is not sufficient for PfAtg8 apicoplast function. Other regions previously implicated in canonical Atg8 interactions, the ubiquitin-interacting motif (UIM) docking site (UDS) and the N-terminal helix are not required for PfAtg8 function. Finally, the unique Apicomplexan-specific loop previously implicated in interaction with membrane conjugation machinery in vitro, is not required in vivo neither for membrane conjugation nor for the effector function of PfAtg8. These results suggest that the effector function of PfAtg8 is mediated by structural features distinct from those previously identified for macroautophagy and selective autophagy functions.ImportanceThe most extensively studied role of Atg8 proteins is in autophagy. However, it is clear that they have other non-autophagic functions critical to cell function and disease pathogenesis yet understudied compared to their canonical role in autophagy. Mammalian cells contain multiple Atg8 paralogs that have diverse, specialized functions. Gaining molecular insight into their non-autophagic functions is difficult because of redundancy between the homologs and their role in both autophagy and non-autophagic pathways. Malaria parasites such as Plasmodium falciparum are a unique system to study a novel, non-autophagic function of Atg8 separate from its role in autophagy: They have only one Atg8 protein whose only essential function is in the inheritance of the apicoplast, a unique secondary plastid organelle. Insights into the molecular basis of PfAtg8’s function in apicoplast biogenesis will have important implications for the evolution of diverse non-autophagic functions of the Atg8 protein family.

Non-alcoholic fatty liver disease (NAFLD) is a significant clinical and epidemiological problem that affects around 25% of the adult global population. A large body of clinical evidence highlights that NAFLD is associated with increased liver-related morbidity and mortality and an increased risk of cardiovascular disease, extrahepatic cancers, type 2 diabetes, and chronic kidney disease. Recently, a series of studies revealed the pivotal role of gut microbiota (GM) dysbiosis in NAFLD’s pathogenesis. The GM plays an essential role in different metabolic pathways, including the fermentation of diet polysaccharides, energy harvest, choline regulation, and bile acid metabolism. One of the most critical factors in GM stabilization is the diet; therefore, nutritional therapyappearsto be a promising tool in NAFLD therapy. This paper aims to review the current knowledge regardingthe nutritional approach and its implications with GM and NAFLD treatment. We discuss the positive impact of probiotics, prebiotics, and symbiotics in a reverse dysbiosis state in NAFLD and show the potential beneficial effects of bioactive substances from the diet. The full description of the mechanism of action and comprehensive examination of the impact of nutritional interventions on GM modulation may, in the future, be a simple but essential tool supporting NAFLD therapy.

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From our previous research among bus drivers, in difficult, but not extreme situations, we observed an increase in blood pressure (up to 200mm Hg), cardiac arrhythmias, ischemia, etc. Such reactions may be dangerous to healthy people, but they are extremely risky for drivers with a history of cardiovascular or cerebrovascular incidents. Thus, certifying driving ability of such persons is a serious problem for the medical expert. In this case, tests in a driving simulator, where it is possible to arrange a variety of stressful situations and also to monitor the reaction of the cardiovascular system and brain electrical activity may be a great advantage. Therefore we developed a first-in-Poland integrated system for examination and training of road vehicle drivers, including model stand for simulating of driving vehicle under conditions of road traffic, and a set of methods of psychological and physiological tests to be applied for testing drivers. This simulator enables to assess physiological response to different traffic situations, to analyze the effects of work environment on psychical and physical abilities of drivers, to test the feasibility of the physiological methods for assessing the fatigue and drowsiness, to evaluate the effect of monotony and static loads on the development of driver's fatigue, to assess changes in psychomotor abilities of drivers resulting from exposure to harmful and noxious agents at workplace.

A group of professional bus drivers have done two rides on a city bus simulator – the fist one into the city centre and the other one in the suburbs. One dangerous incident was simulated during each ride. The visual strategy was evaluated by the FaceLab system comprising two pairs of cameras, one facing the road and the other to the left side. The main selected criteria of the visual strategy included the number and duration of gaze fixations. Furthermore, eyelid movements (PERCLOS index) and pupil diameter were recorded. The results were subjected to a statistical analysis.

Equine behaviour is crucial for all kinds of equestrian activities, and therefore behavioural traits are considered as selection criteria in horse breeding programs in many countries. Since neither a desired profile of equine personality for particular riding disciplines nor detailed preferences of different groups of equestrians have been clearly established, the aims of the present study were: personality model development, establishing of equestrians preferences regarding this model, and determination of general equestrians’ opinions on the subject. The personality model proposed here, based on the opinions of 16 experienced equestrians (two independent expert groups), classifies equine personality into temperament and character. Combining the results with existing human personality models we define temperament as simple, innate properties of the nervous system, whereas character includes complex features acquired through learning. Four dimensions were distinguished for temperament: energy (tEN), fearfulness (tFR), sensitivity (tSN), adaptability (tAD), and four other dimensions for character: submissiveness (cSB), aggression (cAG), human contact seeking (cCS) and self-reliance (cSR). These dimensions were used to establish a desired equine personality profile. A Survey on Equine Personality was completed by 701 women and 100 men, representing 15 professions and 10 disciplines. Respondents were of the opinion that psychological traits are equally important for success in equestrian sports as physical traits (Chi-square test: X = 3.15; P = 0.21). All dimensions were assessed as important or very important (Median ≥ 4 on 1–5 scale). Our study not only refutes common beliefs that there is some mismatch between leisure and sport riders’ expectations, but also indicates in detail a desired personality profile which includes high tEN, tSN, tAD, cSB, cCS, cSR; low tFR and cAG, regardless a respondent’s discipline, age, gender, profession and level of experience or qualification. Respondents declared that present breeding selection for behavioural traits in Poland, lacking clear criteria like in Germany, is not efficient (X = 478; P

Endosymbiosis has driven major molecular and cellular innovations. Plasmodium spp. parasites that cause malaria contain an essential, non-photosynthetic plastid—the apicoplast—which originated from a secondary (eukaryote–eukaryote) endosymbiosis. To discover organellar pathways with evolutionary and biomedical significance, we performed a mutagenesis screen for essential genes required for apicoplast biogenesis in Plasmodium falciparum. Apicoplast(−) mutants were isolated using a chemical rescue that permits conditional disruption of the apicoplast and a new fluorescent reporter for organelle loss. Five candidate genes were validated (out of 12 identified), including a triosephosphate isomerase (TIM)-barrel protein that likely derived from a core metabolic enzyme but evolved a new activity. Our results demonstrate, to our knowledge, the first forward genetic screen to assign essential cellular functions to unannotated P. falciparum genes. A putative TIM-barrel enzyme and other newly identified apicoplast biogenesis proteins open opportunities to discover new mechanisms of organelle biogenesis, molecular evolution underlying eukaryotic diversity, and drug targets against multiple parasitic diseases., The apicoplast of the malaria parasite Plasmodium falciparum provides critical metabolites during host cell infection. An unbiased forward genetic screen identifies previously unknown genes required for biogenesis of this organelle, potentially yielding novel antimalarial drug targets., Author summary Plasmodium parasites, which cause malaria, and related apicomplexan parasites evolved from photosynthetic algae that acquired their chloroplast through two successive endosymbioses. Although no longer photosynthetic, the apicomplexan plastid—or apicoplast—was retained in these pathogens and provides critical metabolites during host cell infection. The apicoplast is of major interest for its unique biology and potential to yield new antimalarial drug targets. Here, we focused on the critical genes required to grow, divide, and inherit new apicoplasts during parasite replication. Given the apicoplast’s divergent evolution, most of these cannot be recognized by their homology to genes with known functions. Instead, we overcame significant technical challenges in the Plasmodium experimental system to perform an unbiased screen to search for these critical genes. Our screen has uncovered new genes with intriguing evolution and function that open up opportunities to understand and ultimately exploit apicoplast biology. Finally, assigning new, essential gene functions in Plasmodium parasites remains a daunting task. The successful identification of essential gene functions using an unbiased approach in this study provides a viable route for expansion of this screen or developing screens for other novel Plasmodium pathways in the future.

The aim of this preliminary study was to assess whether adult stallions differentiate their olfactory and marking behavior toward the excreta of potential rivals depending on their age, libido, hormonal status, and the season of the year. Five Konik stallions were individually exposed to own and each others' feces in a round pen during 8 observation sessions from February to November. The youngest stallion's feces were sniffed for a significantly longer period and were defecated or urinated on significantly more often, in addition to receiving more flehmen reactions. The stallion with the highest libido sniffed feces significantly longer. Alien feces were sniffed significantly longer than an individual's own feces, except for the youngest stallion. Overmarking of existing feces with urine was significantly less frequent than through defecation and was observed only outside of the reproductive season. Defecations on feces were most frequent after the peak of the reproductive season. A stallion's libido rank correlated perfectly with the number of defecations performed on alien feces (r s = 1.000). Sniffing of feces occurred for a longer time before the peak of the reproductive season, and flehmen was performed primarily on spots around feces and significantly more often in the peak of the reproductive season (May). Fecal testosterone and androstenedione concentrations were significantly higher in April and May but did not differ significantly between stallions. Testosterone concentrations were positively correlated with duration of performed sniffing feces and negatively correlated with the duration the individual's feces were sniffed. It was for the first time shown which individual social information could be mediated by defecation and sniffing feces in adult stallions.

During the illness are released volatile organic compounds with specific smell which could have in diagnosis of diseases. The first aim of the study was qualitative and quantitative analysis of exhaled breath samples obtained from patients with lung cancer, healthy volunteers and people with other lung diseases by gas chromatography-mass spectrometry. This study showed that twenty compounds propane, ethanol, isobutane, butane, propanal, 1-propanol, 2-propanol, 2-methylfuran, 2-butanone, benzene, 2-pentanone, pentanal, hexanal, cyclohexanone, 4-heptanone, 2,4-dimethylheptane, 2,3,4-trimethylhexane, 2,3,5-trimethylhexane, 4-methyloctane, α-pinene separated two research groups of patients and healthy controls. The second goal was to evaluate the sensitivity and specificity of canine scent detection using 5 station scent lineup. Among lung cancer patients and complementary samples, overall sensitivity of canine scent detection was 85.54%, while specificity was 71.84%.

Genetic diseases occur in breeds used for law enforcement. As important team members, dogs are expected to operate at peak performance for several years and are significant investments for both the initial purchase and extensive, specialized training. Previous studies have not focused on causes for retirement or euthanasia as genetic (inherited) versus acquired (environmental). We performed direct mutational analysis for breed-specific conditions on samples from 304 dogs including 267 law enforcement (122 US, 87 Israeli, and 58 Polish) and 37 search and rescue dogs. Genetic testing identified 29% (n = 89) of the dogs tested to be carriers of a genetic mutation and 6% (n = 19) to be at risk for a debilitating inherited condition that may eventually impair the dog's ability to work. At-risk dogs included Labrador Retrievers (n = 4) with exercise-induced collapse, Bloodhounds (n = 2) with degenerative myelopathy (DM), and German Shepherd dogs with DM (n = 12) or leukocyte adhesion deficiency, type III (n = 1). A substantial number of working dogs were shown to be at risk for genetic conditions that may shorten the dog's career. The loss of dogs, due to early retirement or euthanasia, as a result of preventable genetic conditions has an emotional cost to handlers and financial cost to service organizations that can be avoided with genetic screening prior to breeding, buying, or training.

The main aim of the study was qualitative and quantitative analysis of volatile organic compounds (VOCs) occurring in biological samples such as exhaled air obtained from 108 patients with lung cancer, 121 healthy volunteers, and 24 persons with other lung diseases. For determination of VOCs in human breath, solid phase microextraction and gas chromatography–mass spectrometry (SPME/GC–MS) were applied. Statistical methods such as artificial neural network and chi-squared automatic interaction detector (CHAID) were applied for data evaluation. The concentration of acetone, isoprene, ethanol, 1-propanol, 2-propanol, hexanal, and dimethyl sulfide were higher in patients with lung cancer than in case of healthy volunteers and persons with other lung diseases. The second goal was the application of trained dogs for detection of the same breath samples as in GC–MS research and evaluate the sensitivity and specificity of canine scent detection using 5 station scent lineup. Among lung cancer patients and complementary samples, overall sensitivity of canine scent detection was 86%, while specificity was 72%. There is a possibility that in the future these methods could allow for a fast, painless, and noninvasive diagnosis of cancer.

Some recent publications claim that the effectiveness of police canine drug detection is uncertain and likely minimal, and that the deterrent effect of dogs on drug users is low. It is also claimed that more scientific evidence is needed to demonstrate to what extent dogs actually detect drugs. The aim of this research was to assess experimentally, but in actual training and testing environments used by the Polish police, how effective dogs trained by the police were at illicit substance detection depending on factors such as type of drug, dog breed, dog experience with the searching site, and drug odor residuals. 68 Labrador retrievers, 61 German shepherds, 25 Terriers and 10 English Cocker Spaniels, of both sexes in each breed, were used. Altogether 1219 experimental searching tests were conducted. On average, hidden drug samples were indicated by dogs after 64s searching time, with 87.7% indications being correct and 5.3% being false. In 7.0% of trials dogs failed to find the drug sample within 10min. The ranking of drugs from the easiest to the most difficult to detect was: marijuana, hashish, amphetamine, cocaine, heroin. German shepherds were superior to other breeds in giving correct indications while Terriers showed relatively poor detection performance. Dogs were equally efficient at searching in well-known vs. unknown rooms with strange (i.e., non-target novelty) odors (83.2% correct indications), but they were less accurate when searching outside or inside cars (63.5% and 57.9% correct indications respectively). During police examination trials the dogs made more false alerts, fewer correct indications and searching time was longer compared to the final stage of the training. The drug odor may persist at a site for at least 48h. Our experiments do not confirm the recent reports, based on drug users' opinions, of low drug detection efficiency. Usefulness of drug detection dogs has been demonstrated here, even if their effectiveness may not be 100%, but different factors have to be taken into consideration to assure maximum effectiveness.

Autophagy is a conserved process for the bulk degradation of cytoplasmic material. Triggering of autophagy results in the formation of double membrane-bound vesicles termed autophagosomes. The conserved Atg5–Atg12/Atg16 complex is essential for autophagosome formation. Here, we show that the yeast Atg5–Atg12/Atg16 complex directly binds membranes. Membrane binding is mediated by Atg5, inhibited by Atg12 and activated by Atg16. In a fully reconstituted system using giant unilamellar vesicles and recombinant proteins, we reveal that all components of the complex are required for efficient promotion of Atg8 conjugation to phosphatidylethanolamine and are able to assign precise functions to all of its components during this process. In addition, we report that in vitro the Atg5–Atg12/Atg16 complex is able to tether membranes independently of Atg8. Furthermore, we show that membrane binding by Atg5 is downstream of its recruitment to the pre-autophagosomal structure but is essential for autophagy and cytoplasm-to-vacuole transport at a stage preceding Atg8 conjugation and vesicle closure. Our findings provide important insights into the mechanism of action of the Atg5–Atg12/Atg16 complex during autophagosome formation.

Finding a non-invasive, painless and simple screening method for early detection of cancer is a desirable goal. There is evidence that volatile organic compounds (VOCs) detectable in exhaled air and producing specific breath odor could be taken into consideration as possible cancer markers. Chemical analysis of VOCs in the breath that utilizes gas chromatography-mass spectrometry or an array of specific sensors (an electronic nose) could be useful for cancer screening. Preliminary reports show that canines, due to their extraordinary sense of smell and ability to perform well with operant conditioning, could also be used in the future as biological screeners for different forms of cancer. However, the question remains open whether specific VOCs or breath odors appear at very early (sub-clinical) stages of cancer disease or only at advanced stages of the disease during tumor decomposition.

The aim of this study was to assess the progress in operant conditioning of dogs during 3 training phases up to a level where the dogs performed a minimum of 40 correct indications without false alerts and hesitations in at least 100 trials in each phase, and to compare the training results with the working phase. Breath samples from 57, 45, and 118 patients with breast cancer, melanoma, and lung cancer, respectively, were used as patterns, with samples from 305 healthy volunteers as controls. Six dogs in 2 age-groups (20 months vs. 6 months old) were used for the training. In phase I, the dogs were trained to indicate by sitting or lying down before the breath samples taken from cancer patients (pattern odor) coupled with food odor and placed among 4 blank samples (a lineup of 5 samples). In phase II, a pattern sample without food odor was placed among blank samples. In phase III as well as in the working phase, a pattern sample was placed among control samples. Significant individual differences were found in dogs' performance during the training. The percentage of trials with prompts to achieve self-dependent work decreased in older dogs in consecutive training phases, but increased in phase II in the younger dogs. The increasing level of challenge in consecutive training phases resulted in a higher percentage of false alerts and misses, and in younger dogs, decreased motivation for sniffing the odor samples was observed in training phase III. Nonsignificant and negative correlations between the training phases and working phase in the percentage of correct indications and false alerts show that it is difficult to predict the performance of fully trained dogs on the basis of the results achieved during the training. Fully trained dogs discriminated pattern breath samples (cancer) from healthy controls with 79% sensitivity and 78% specificity, or with 50% sensitivity at the probability of correct response by chance of 50% and 20%, respectively. The sensitivity decreased to 68% and 37%, respectively, when each sample was tested only once, although being better than by chance ( P

In this work, a chromatographic method for identification of volatile organic compounds was compared with canine recognition. Gas chromatography and mass spectrometry (GC–TOF MS) were used for determination of concentrations of trace gases present in human breath. The technique enables rapid determination of compounds in human breath, at the parts per billion level. Linear correlations were from 0.83–234.05 ppb, the limit of detection was the range 0.31–0.75 ppb, and precision, expressed as relative standard deviation (RSD), was less than 10.00 %. Moreover, trained dogs are able to discriminate breath samples of patients with diagnosed cancer. We found a positive correlation between dog indications and the ethyl acetate and 2-pentanone content of breath (r = 0.85 and r = 0.97, respectively). The methods presented for detection of lung cancer markers in exhaled air could be used as a potential non-invasive tool for screening. In addition, the canine method is relatively simple and inexpensive in comparison with chromatography.

Scent identification lineups using dogs are a potentially valuable forensic tool, but have been dismissed by some critics because ofcases where a false identification was shown to have occurred. It is not known, however, why dogs appear to make more false indications to theodors of some persons than of others. In this study, human genders were compared as to the degree their individual odors are distinguishable or‘‘attractive’’ to dogs. Six dogs were trained to smell an individual ’s hand odor sample and then find the matching hand odor sample in a lineup offive odors. Using one-gender lineups and two-gender lineups with different gender ratios, it was found that dogs trained for the study identified ind i-vidual women’s hand odors more accurately than those of men. It is hypothesized th at this is either because of differences in chemical compoundsmaking discrimination of women’s odors easier, or because of greater ‘‘odor attractiveness’’ of women’s scents to dogs. KEYWORDS

Rationale Acute calculous cholecystitis is a prevalent disease whose diagnosis and management still face significant debate. Although the overall incidence of gallstone disease is 18.8% in European women aged 30 to 69 years, there is little data and experience in managing acute calculous cholecystitis in populations over 80 years old. The incidence of acute cholecystitis among the elderly is probably increasing. For the reason, we here highlight the advantages and disadvantage of various treatment and management opens based on a 96-year-old patient. Patient concerns We present a rare case in which a 96-year-old woman suffered from abdominal pain, nausea, and lack of appetite for over a month. Diagnoses She was diagnosed with acute calculous cholecystitis and pancreatitis. Interventions She was successfully treated without surgery, regaining her physical health after 5 months. Outcomes The question of how to manage acute calculous cholecystitis is extremely difficult in many aspects. The patient of very advanced age presented in this paper, not very well diagnosed and with a life-threating condition, survived because of careful treatment and reasonable decision-making. Lessons The take-away from this case is that, in a high-risk senile patient, strict conservative therapy of cholecystitis may be successful, as it can avoid the complications of surgery and leave the patient with a good quality of life.

The outstanding sensitivity of the canine olfactory system has been acknowledged by using sniffer dogs in military and civilian service for detection of a variety of odors. It is hypothesized that the canine olfactory ability is determined by polymorphisms in olfactory receptor (OR) genes. We investigated 5 OR genes for polymorphic sites which might affect the olfactory ability of service dogs in different fields of specific substance detection. All investigated OR DNA sequences proved to have allelic variants, the majority of which lead to protein sequence alteration. Homozygous individuals at 2 gene loci significantly differed in their detection skills from other genotypes. This suggests a role of specific alleles in odor detection and a linkage between single-nucleotide polymorphism and odor recognition efficiency.

Cystinuria is a purely renal, rare genetic disease caused by mutations in cystine transporter genes and characterized by defective cystine reabsorption leading to kidney stones. In 14% of cases, patients undergo nephrectomy, but given the difficulty to predict the evolution of the disease, the identification of markers of kidney damage would improve the follow-up of patients with a higher risk. The aim of the present study is to develop a robust, reproducible, and noninvasive methodology for proteomic analysis of urinary exosomes using high resolution mass spectrometry. A clinical pilot study conducted on eight cystinuria patients versus 10 controls highlighted 165 proteins, of which 38 were up-regulated, that separate cystinuria patients from controls and further discriminate between severe and moderate forms of the disease. These proteins include markers of kidney injury, circulating proteins, and a neutrophil signature. Analysis of selected proteins by immunobloting, performed on six additional cystinuria patients, validated the mass spectrometry data. To our knowledge, this is the first successful proteomic study in cystinuria unmasking the potential role of inflammation in this disease. The workflow we have developed is applicable to investigate urinary exosomes in different renal diseases and to search for diagnostic/prognostic markers. Data are available via ProteomeXchange with identifier PXD001430.

Gas chromatography and mass spectrometry (GC/MS) was applied for determination of concentrations volatile organic compounds present in human breath samples. The technique allows to rapid determination compounds in human air, at the level of parts per billion. It showed linear correlations ranging from 0.83-234.05 ppb, limit detection in the range of 0.31-0.75 ppb and precision, expressed as RSD, was less then 10.00%. Moreover, trained dogs are able to discriminate breath samples of patients with diagnosed cancer disease. We found positive correlation between dog indications and content of ethyl acetate and 2- pentanone in breath (r=0.85 and r=0.97, respectively)

Condensin complexes have central roles in the three-dimensional organization of chromosomes during cell divisions, but how they interact with chromatin to promote chromosome segregation is largely unknown. Previous work has suggested that condensin, in addition to encircling chromatin fibers topologically within the ring-shaped structure formed by its SMC and kleisin subunits, contacts DNA directly. Here we describe the discovery of a binding domain for double-stranded DNA formed by the two HEAT-repeat subunits of the Saccharomyces cerevisiae condensin complex. From detailed mapping data of the interfaces between the HEAT-repeat and kleisin subunits, we generated condensin complexes that lack one of the HEAT-repeat subunits and consequently fail to associate with chromosomes in yeast and human cells. The finding that DNA binding by condensin's HEAT-repeat subunits stimulates the SMC ATPase activity suggests a multistep mechanism for the loading of condensin onto chromosomes.

Qualitative and quantitative changes in dogs’ information-seeking behaviours during the subsequent phases of operant conditioning training using a scent lineup, were investigated. Particular interest was paid to behaviours which may have an impact on errors committed by dogs at work in a scent lineup and thus on the reliability of the canine identification of humans on the base of scent. Significant individual differences were found in dogs’ performance in operant conditioning during match-to-sample trials. The style and time of sniffing the pattern scent sample as well as the searching time and number of stations sniffed in the lineup were found to influence the percentage of errors (false positive and false negative indications) made by dogs. The effects of the dogs’ routine e.g. omitting stations, using other cues than olfactory ones (visual) and effects of the non-verbal communications between handler and dog have been discussed.

The aim of the study was to determine the parents view and attitude to the universal neonatal hearing screening.parents of randomly selected 200 infants, who underwent hearing rescreening, were surveyed using the authors questionnaire.the universal neonatal hearing screening and the way it is conducted is accepted by the vast majority of the parents in the region of Wielkopolska. The parents with higher social and economic status express their negative emotions associated with the organisation of hearing screening more often, their expectations towards the system of medical care are rising.the newborn hearing screening has been a good stimulus for parents intently observation of their child auditory reaction.

Experimental studies using trained dogs to identify breath odour markers of human cancer, published in the recent decade, have been analyzed and compared with the authors' own results. Particular published studies differ as regards the experimental setup, kind of odour samples (breath, urine, tumor tissue, serum), sample collection methods, dogs' characteristics and dog training methods as well as in results presented in terms of detection sensitivity and specificity. Generally it can be stated that trained dogs are able to distinguish breath odour samples typical for patients with lung cancer and other cancers from samples typical for healthy humans at a 'better than by chance' rate. Dogs' indications were positively correlated with content of 2-pentanone and ethyl acetate (r = 0.97 and r = 0.85 respectively) and negatively correlated with 1-propanol and propanal in breath samples (r = -0.98 and -0.87 respectively). The canine method has some advantages as a potential cancer-screening method, due to its non-invasiveness, simplicity of odour sampling and storage, ease of testing and interpretation of results and relatively low costs. Disadvantages and limitations of this method are related to the fact that it is still not known exactly to which chemical compounds and/or their combinations the dogs react. So far it could not be confirmed that dogs are able to sniff out early preclinical cancer stages with approximately the same accuracy as already diagnosed cases. The detection accuracy may vary due to failure in conditioning of dogs, decreasing motivation or confounding factors. The dogs' performance should be systematically checked in rigorous double-blind procedures. Recommendations for methodological standardization have been proposed.

Disorders of voice breaking in adolescent boys (mutational dysphonia) could be a result of local, hormonal, neuropsychiatric or sensual factors. The aim of this paper was the voice assessment of three subjects with incomplete mutation with particular additional factors, disturbing hearing, voice and speech: like hearing loss, hyperfunctional childhood dysphonia and speech dysfluency. Diagnostics included complete phoniatric examination with perceptive estimation, videostroboscopy and acoustic voice analysis, done before and after treatment. Rehabilitation process results were well seen in perceptive and objective voice analysis except significant improvement of fundamental frequency average. Analysis of incomplete mutation etiological factors need special attention due to coexist with another voice, speech and hearing disorders, which undergo with high tension of voice organ muscles or with the lack of phonation auditory feedback.

The report presents three patients with coincidence of voice disorders and rheumatoid arthritis. Material consisted of 3 females aged 39, 48 and 74 years. Methods included phoniatric examination, videolaryngoscopy, stroboscopy and acoustic voice analysis MDVP).In the two youngest patients the laryngoscopic changes were located on vocal folds, mostly as yellow nodules. The appropriate mobility of both vocal folds was found. The MDVP analysis particularly revealed changes in parameters describing perturbation of amplitude in both cases. In the third case oedema in the region of the crico-arytenoid joints and vestibular folds were observed. MDVP analysis showed slight disturbances in the parameters describing frequency perturbation.

The activity of the conserved Atg12–Atg5-Atg16 complex is essential for autophagosome formation. However, little is known about its mechanism of action during this process. In our study we employed in vitro systems consisting of purified proteins and giant unilamellar vesicles (GUVs) or small liposomes to investigate membrane binding by the Atg12–Atg5-Atg16 complex and its interplay with the Atg8 conjugation system. We showed that Atg5 directly binds membranes and that this membrane binding is negatively regulated by Atg12 conjugation but activated by Atg16. Membrane binding by the Atg12–Atg5-Atg16 complex is required for efficient promotion of Atg8 lipidation. Additionally, we found that the Atg12–Atg5-Atg16 complex tethered vesicles in an Atg8-independent manner. In yeast, membrane binding by Atg5 is not required for its recruitment to the phagophore assembly site (PAS) but is essential for efficient promotion of autophagy and the cytoplasm-to-vacuole targeting (Cvt) pathway at a stage preceding Atg8 lipidation and autophagosome closure. Our findings provide new insights into the role of the Atg12–Atg5-Atg16 complex during autophagosome formation.

A case of 4-year-old boy with Wildervanck's syndrome and associated profound sensorineural hearing loss is presented. The child was disqualified from cochlear implantation following the CT scan of petrous pyramids which revealed inner ear malformation. The authors emphasize role of CT imaging in the management of profound sensorineural hearing loss in children before final qualification for cochlear implantation.

The authors present phoniatric voice assessment in 9 cases of laryngeal trauma. Vocal cord immobilisation due to iatrogenic cricoarytenoid subluxation was particularly considered.

A case of a 12-year-old boy with Parry-Romberg syndrome was presented. Speech and hearing disorders impairing communicative process and abnormalities in the ENT examination, ultrasonography of parotid salivary glands, radiological changes of sella turcica were particularly considered.

The aim of the paper was to present voice and speech disorders associated with motor neuron disease-MND. Two cases of MND were described. Communication problems--dysphonia and dysartria were one of their early manifestations. It is supposed that sulcus vocalis, which is the result of the degeneration process of the vocal muscle, is the laryngeal presentation of MND.

We report a case of unilateral sensorineural hearing loss due to Borrelia burgdorferi infection and in a patient with haemophilia B and hepatitis C treated with alpha-interferon. An audiological check-up of that kind of patients is indicated in order to exclude hearing loss.