Novel Gluconobacter oxydans strains selected from Kombucha with potential postbiotic activity.

Gastric and colorectal cancer are among the most frequently diagnosed malignancies of the gastrointestinal tract. Searching for methods of therapy that complements treatment or has a preventive effect is desirable. Bacterial metabolites safe for human health, which have postbiotic effect, are of interest recently. The study aimed to preliminary assessment of the safety, antimicrobial, and anti-cancer activity of cell-free metabolites of Gluconobacter oxydans strains isolated from Kombucha beverages as an example of the potential postbiotic activity of acetic acid bacteria (AAB). The study material consisted of five AAB strains of Kombucha origin and three human cell lines (gastric adenoma-AGS, colorectal adenoma-HT-29, and healthy cells derived from the endothelium of the human umbilical vein-HUVEC). Results of the study confirms the health safety and functional properties of selected AAB strains, including their potential postbiotic properties. The best potential anticancer activity of the AAB cell-free supernatants was demonstrated against AGS gastric adenoma cells. The conducted research proves the postbiotic potential of selected acetic acid bacteria, especially the KNS30 strain. KEY POINTS: •The beneficial and application properties of acetic acid bacteria are poorly studied. •Gluconobacter oxydans from Kombucha show a postbiotic activity. •The best anticancer activity of the G. oxydans showed against gastric adenoma.

Clinical Significance of Nectins in HCC and Other Solid Malignant Tumors: Implications for Prognosis and New Treatment Opportunities-A Systematic Review.

The nectin family comprises four proteins, nectin-1 to -4, which act as cell adhesion molecules. Nectins have various regulatory functions in the immune system and can be upregulated or decreased in different tumors. The literature research was conducted manually by the authors using the PubMed database by searching articles published before 2023 with the combination of several nectin-related keywords. A total of 43 studies were included in the main section of the review. Nectins-1-3 have different expressions in tumors. Both the loss of expression and overexpression could be negative prognostic factors. Nectin-4 is the best characterized and the most consistently overexpressed in various tumors, which generally correlates with a worse prognosis. New treatments based on targeting nectin-4 are currently being developed. Enfortumab vedotin is a potent antibody-drug conjugate approved for use in therapy against urothelial carcinoma. Few reports focus on hepatocellular carcinoma, which leaves room for further studies comparing the utility of nectins with commonly used markers.

Direct-Acting Oral Anticoagulant Therapy in Cancer Patients-A Review.

Venous thromboembolism (VTE) is an important aspect in cancer patients. There are various pharmacological methods used for thrombotic event treatment. DOACs (direct-acting oral anticoagulants) are gaining popularity among both physicians and researchers and are slowly starting to replace VKAs (vitamin K antagonists), thus becoming a substitute or alternative option for LMWHs (low-molecular-weight heparins). In this article, we present DOACs' main therapeutic advantages and disadvantages in patients with cancer. The only major concern with using DOACs is the higher risk of bleeding; however, there are discrepancies in this matter. There are still some types of cancer for which DOACs are not recommended. Specific cancer types may influence the efficacy of DOAC therapy. Additionally, race and ethnicity may affect therapy in cancer patients with DOACs. A sizeable number of clinical trials are focused on comparing DOACs with other anticoagulants. The current guidelines of different scientific associations are not unanimous in their DOAC assessments. There is still a need for more evidence of DOACs' potential advantages over other methods of anticoagulation in cancer patients to facilitate their position in this recommendation. This literature review presents the current state of knowledge about the use of DOACs in patients with neoplastic growth.

Development of Ready-to-Eat Organic Protein Snack Bars: Assessment of Selected Changes of Physicochemical Quality Parameters and Antioxidant Activity Changes during Storage.

Novel organic high-protein bars (HPB) were developed and produced from organic ingredients such as prebiotic and pro-healthy additives or whey protein concentrate (WPC-80). The influence of temperature and time on the selected physicochemical parameters and antioxidant activity of three formulations of HPBs when stored (at 4 °C and 22 °C for 3 months) was investigated. The fresh products varied on the basis of available carbohydrates, crude lipids, amino acid profile, and fatty acid profile resulting from the used formulations. A total of 17 amino acids (AA), including 10 essential amino acids (EAA), were identified in HPBs. The concentrations of all essential amino acids determined by EAA scores (AAS), except Histidine (His), were higher than the FAO/WHO/UNU (2007) pattern; for the WPC-80 however, in the case of the developed HPB, the scores were lower (0.21-0.48). The first limiting amino acid in HPB was Val (Valine). The temperature and time of storage significantly affected the proximate chemical composition and an assessment of the products' antioxidant activity. The amino acid and fatty acid composition of stored products slightly changed. However, stored HPBs had a low content of trans fatty acids (TFAs). The optimal method of storage for the investigated bars was at the temperature of 4 °C for 3 months.

The Usefulness of the C2HEST Risk Score in Predicting Clinical Outcomes among Hospitalized Subjects with COVID-19 and Coronary Artery Disease.

BACKGROUND: Even though coronary artery disease (CAD) is considered an independent risk factor of an unfavorable outcome of SARS-CoV-2-infection, the clinical course of COVID-19 in subjects with CAD is heterogeneous, ranging from clinically asymptomatic to fatal cases. Since the individual C2HEST components are similar to the COVID-19 risk factors, we evaluated its predictive value in CAD subjects. MATERIALS AND METHODS: In total, 2183 patients hospitalized due to confirmed COVID-19 were enrolled onto this study consecutively. Based on past medical history, subjects were assigned to one of two of the study arms (CAD vs. non-CAD) and allocated to different risk strata, based on the C2HEST score. RESULTS: The CAD cohort included 228 subjects, while the non-CAD cohort consisted of 1956 patients. In-hospital, 3-month and 6-month mortality was highest in the high-risk C2HEST stratum in the CAD cohort, reaching 43.06%, 56.25% and 65.89%, respectively, whereas in the non-CAD cohort in the high-risk stratum, it reached: 26.92%, 50.77% and 64.55%. Significant differences in mortality between the C2HEST stratum in the CAD arm were observed in post hoc analysis only for medium- vs. high-risk strata. The C2HEST score in the CAD cohort could predict hypovolemic shock, pneumonia and acute heart failure during hospitalization, whereas in the non-CAD cohort, it could predict cardiovascular events (myocardial injury, acute heart failure, myocardial infract, carcinogenic shock), pneumonia, acute liver dysfunction and renal injury as well as bleedings. CONCLUSIONS: The C2HEST score is a simple, easy-to-apply tool which might be useful in risk stratification, preferably in non-CAD subjects admitted to hospital due to COVID-19.

Acceptance of illness, quality of life and nutritional status of patients after lower limb amputation due to diabetes mellitus.

INTRODUCTION: Diabetes mellitus is one of the most common chronic diseases with a high number of sufferers worldwide. Diabetic neuropathy and diabetic angiopathy lead to serious infectious complications which are very difficult to combat and may finally lead to the amputation of a lower limb. The aim of the study was to evaluate the quality of life, the level of acceptance of the illness and the nutritional status of patients after lower limb amputation due to diabetes. METHODS: Ninety-nine patients (23 men and 76 women) were enrolled into the study. They had all undergone lower limb amputation due to diabetic foot and were treated in the Department of General and Oncological Surgery. The following questionnaires were used: the WHO Quality of Life-BREF (WHOQOL-BREF), the Mini Nutritional Assessment (MNA), the Acceptance of Illness Scale (AIS) and the anonymous specific socio-demographic characteristics questionnaire. RESULTS: The diabetes-related amputees were revealed to have a higher QoL within the social domain (mean score 64.48), an intermediate QoL - within the environmental domain (mean score 63.04) and the mental domain (mean score 59.61), and a lower QoL - within physical (somatic) domain (mean score 54.69). There was no statistical correlation between genders or between all the domains of QoL (P > 0.05). The mean MNA score was 22.66, which means that patients were at risk of malnutrition. There were statistical differences between women and men as regards nutritional status (P = 0.034). The mean AIS score was 27.65 (27.09 women and 29.48 men), which means that the respondents accept their disease. There was no statistical correlation between gender and the acceptance of the disease (P = 0.288). There was not statistical correlation between age and QoL (P > 0.05). There were statistical differences between age and nutritional status (P < 0.05), and between age and acceptance of the illness (P = 0.044). CONCLUSIONS: The better the quality of life was in all the domains, the better the level of acceptance of illness was. The less malnourished the patient was, the better their quality of life was in all the domains.

Exhausted Capacity of Bicarbonate Buffer in Renal Failure Diagnosed Using Point of Care Analyzer.

BACKGROUND: Metabolic acidosis in patients with chronic kidney disease (CKD) is a common complication. A bicarbonate concentration in venous blood (V-HCO3-) is a key index for diagnosis and treatment initiation. The aim of our study is to evaluate usability of acid-base balance parameters of in blood taken simultaneously from peripheral artery and the vein. METHODS: A total of 49 patients (median age 66 years [interquartile range IQR 45-75]), with CKD stage G4 or G5 were enrolled in this cross-sectional study. All patients were qualified for arteriovenous fistula creation in pre-dialysis period. The samples were taken during surgery, directly after dissection, and evaluated in a point of care testing analyzer. The arteriovenous difference in bicarbonate levels (Δ-HCO3-) was calculated. According to glomerular filtration rate (eGFR) the group was divided into Group A eGFR ≥ 10 mL/min/1.73 m2) and Group B eGFR < 10 mL/min/1.73 m2). RESULTS: In Group A Δ-HCO3- was significantly higher compared to Group B. No such differences were observed in the case of V-HCO3-. Δ-HCO3- positively correlated with eGFR. The discriminative power of Δ-HCO3- for predicting eGFR < 10 mL/min/1.73 m2 was 0.72 (95% confidence interval [CI] = 0.551-0.88; p = 0.01) which provided 67% sensitivity and 75% specificity. The best cut-off was 0.5 mmol/L. CONCLUSIONS: The Δ-HCO3- lower than 0.5 mmol/L may be used as predictor of exhaust buffer capacity. The value of this tool should be tested in larger population.

Growth and adhesion inhibition of pathogenic bacteria by live and heat-killed food-origin Lactobacillus strains or their supernatants.

The study aimed to evaluate qualitatively and quantitatively the antimicrobial capacity of 10 potential probiotic Lactobacillus strains against model enteropathogens and spoilage microorganisms. The probiotic strains (live and heat-killed forms) were also assessed for their ability to inhibit adhesion of selected pathogens to Caco-2 cells. The largest inhibition zones (the diffusion method) were connected with the usage of whole bacteria cultures (WBC), also high and moderate with cell-free supernatant (CFS) and the lowest with cell-free neutralized supernatant (CNS). The highest antagonistic activity of Lactobacillus strains was observed against L. monocytogenes strains, moderate activity against Salmonella, Shigella, Escherichia coli, Pseudomonas and, the lowest against S.aureus, Bacillus and Enterococcus. The inhibition of adhesion to Caco-2 cells was very high in the case of E. coli, Salmonella and L. monocytogenes, and moderate in the case of S.aureus. On average, the inhibition effect was higher when pathogenic bacteria were treated by WBC, than heat-killed Lactobacillus. Although, in most samples, the effect was not significantly different (P> 0.05). The strains Lb. brevis O24 and Lb. rhamnosus K3 showed the biggest overall antimicrobial properties, and were most effective in adherence inhibition of investigated indicator strains. These bacteria or their metabolites can be used for the production of various foods or pharmaceutical products.

Turmeric and Its Major Compound Curcumin on Health: Bioactive Effects and Safety Profiles for Food, Pharmaceutical, Biotechnological and Medicinal Applications.

Curcumin, a yellow polyphenolic pigment from the Curcuma longa L. (turmeric) rhizome, has been used for centuries for culinary and food coloring purposes, and as an ingredient for various medicinal preparations, widely used in Ayurveda and Chinese medicine. In recent decades, their biological activities have been extensively studied. Thus, this review aims to offer an in-depth discussion of curcumin applications for food and biotechnological industries, and on health promotion and disease prevention, with particular emphasis on its antioxidant, anti-inflammatory, neuroprotective, anticancer, hepatoprotective, and cardioprotective effects. Bioavailability, bioefficacy and safety features, side effects, and quality parameters of curcumin are also addressed. Finally, curcumin's multidimensional applications, food attractiveness optimization, agro-industrial procedures to offset its instability and low bioavailability, health concerns, and upcoming strategies for clinical application are also covered.

The use of different dialysis membranes in therapy of patients with multiple myeloma.

Free light chains accumulation is the reason of kidney injury in patients with multiple myeloma. The removal of free light chains can improve patients prognosis and survival, and in some cases allows for dialysotherapy discontinuation. Unfortunately, conventional dialysis is not effective enough in terms of free light chains removal. New high cut-off (HCO) techniques remove free light chains more effectively than conventional dialysis. In some cases, this technique may turn out better than hemodiafiltration. However, there are some differences between specific techniques in the removal of kappa and lambda light chains. Lambda light chains are better removed by polymethyl methacrylate membranes with a change of filter during dialysis. Kappa light chains are thoroughly removed by polymethyl methacrylate membranes and HCO (35,000 Da) polysulfone membranes. Unfortunately, it is very difficult to differentiate between the effect of HCO dialysis therapy and concomitant chemotherapy because some of the data is not fully conclusive. Using the proper technique for an individual patient may give optimally effective treatment results.

Functional Properties of Food Origin Lactobacillus in the Gastrointestinal Ecosystem-In Vitro Study.

In the current study, the probiotic activity of ten Lactobacillus (Lb.) strains, previously isolated from the traditional Polish fermented vegetable, was characterized. Strains were assessed for adhesion to human intestinal epithelial Caco-2 cells and regulation of selected cytokine production (IL-1ß, IL-6, IL-10, IL-23, and TNF-α) by THP-1 macrophages. The effect of tested strains on Caco-2 cell apoptosis was also investigated using a caspase-3 assay. Adhesion capacity was strain-dependent (1.29-8.24% of initial population). Highest adhesion was observed for Lb. brevis O24. All Lactobacillus strains investigated in this study stimulated two- to threefold increase in TNF-α, IL-1ß, and IL-6 production, compared to the control. Additionally, selected strains of Lactobacillus caused a significant decrease of pro-inflammatory cytokine production by lipopolysaccharide (LPS)-stimulated THP-1 cells. Almost all Lactobacillus investigated in this study are potent stimulators of IL-10 production. All tested Lactobacillus cells slightly increased the caspase-3 activity in Caco-2 cells. Lb. casei O18 was the most inducing strain. The tested strains had no effect on staurosporine (STS)-induced caspase-3 activity. According to these results, the most promising strains are Lb. plantarum O20, two strains Lb. brevis O22 and O24, and Lb. rhamnosus K3. These newly identified lactobacilli hold promise for use as probiotics in functional food applications.

Food-Origin Lactic Acid Bacteria May Exhibit Probiotic Properties: Review.

One of the most promising areas of development in the human nutritional field over the last two decades has been the use of probiotics and recognition of their role in human health and disease. Lactic acid-producing bacteria are the most commonly used probiotics in foods. It is well known that probiotics have a number of beneficial health effects in humans and animals. They play an important role in the protection of the host against harmful microorganisms and also strengthen the immune system. Some probiotics have also been found to improve feed digestibility and reduce metabolic disorders. They must be safe, acid and bile tolerant, and able to adhere and colonize the intestinal tract. The means by which probiotic bacteria elicit their health effects are not understood fully, but may include competitive exclusion of enteric pathogens, neutralization of dietary carcinogens, production of antimicrobial metabolites, and modulation of mucosal and systemic immune function. So far, lactic acid bacteria isolated only from the human gastrointestinal tract are recommended by the Food and Agriculture Organization (FAO) and World Health Organization (WHO) for use as probiotics by humans. However, more and more studies suggest that strains considered to be probiotics could be isolated from fermented products of animal origin, as well as from non-dairy fermented products. Traditional fermented products are a rich source of microorganisms, some of which may exhibit probiotic properties. They conform to the FAO/WHO recommendation, with one exception; they have not been isolated from human gastrointestinal tract. In light of extensive new scientific evidence, should the possibility of changing the current FAO/WHO requirements for the definition of probiotic bacteria be considered?

Prophylactic salpingo-oophorectomy in BRCA1 mutation carriers and postoperative incidence of peritoneal and breast cancers.

BACKGROUND: There are no effective methods of diagnosis of early-stage ovarian cancer. Conservative care over patients at high risk of ovarian and breast cancers is ineffective. Prophylactic surgery is considered the best prophylaxis among BRCA1/BRCA2 carriers. METHODS: One hundred ninety-five patients, carriers of one of three most common mutations of the BRCA1 gene (Am J Hum Genet: 66: (6)1963-1968, 2000) in the Polish population (5382insC, 4153delA and C61G), who undergone prophylactic salpingo-oophorectomy. The study group consisted of consecutive mutation carriers living in Poland, in the West Pomeranian province. Histopathological examination of the surgical material failed to reveal presence of malignancy. RESULTS: During follow-up we diagnosed two peritoneal cancers and 14 breast cancers. Diagnosis of breast cancer before prophylactic surgery increased the risk of peritoneal cancer almost three times. Time from diagnosis of breast cancer to prophylactic surgery increased the risk of peritoneal cancer after prophylactic surgery. This was strongly expressed (HR = 5.0; p = 0.030) in cases of over five-year-long delay in prophylactic surgery. Diagnosis of breast cancer before prophylactic surgery correlated with the risk of death (p = 0.00010). Presence of 5382insC mutation decreased and C61G mutation increased the risk of peritoneal cancer (p = 0.049 vs. p = 0.013). CONCLUSIONS: Occurrence of primary peritoneal cancer after prophylactic surgery is similar to that reported in international literature. Primary breast cancer occurred less often than in international literature. We suspect that the risk of development of breast cancer among BRCA1 carriers undergoing prophylactic surgery can differ in a population. The next goal should be to study the molecular basis for the risk of development of malignancies in any population. Carriers of BRCA1 gene diagnosed with breast cancer should undergo prophylactic surgery within five years from the diagnosis of breast cancer.

A clinical psychologist's perspective of mental disorders in patients of 70 years of age or more, who underwent digestive tract cancer surgeries.

INTRODUCTION: Behavioural and psychological disorders in surgical patients treated for malignant diseases are not always adequately appreciated and often neglected. However, they are very important in the therapeutic process because they may severely disturb physical and psychological rehabilitation, the patient's effective struggle with malignancy, environmental relationships and quality of life. Professional preoperative psychological assessment is necessary to facilitate therapy for malignant diseases in those patients who are specifically exposed to a severely stressful situation. AIM: To investigate the incidence of depression, hallucinations and anxiety in patients undergoing surgery for malignancy of the digestive tract. The influence of those disorders on the period of hospitalisation, cooperation with medical staff and postoperative quality of life was analysed. MATERIAL AND METHODS: A routine program of psychological and psychiatric care for patients with malignancy, who undergo extensive surgical procedures, was implemented in our department several years ago. The program allows for identification of patients with a high risk of psychiatric disorders to provide them with special psychological support. Sixty-nine patients with advanced malignancy were followed after the surgery between 2009 and 2010. All were examined by a professional psychologist. A QLQ C-30 (EORTC) questionnaire was used to assess the quality of life. RESULTS: Psychotic disorders were present in 53.6% of examined patients. Depression was dominating (57%), followed by anxiety (28%) and hallucinations (15%). The mean hospital stay was different between those, respectively, with and without psychotic disorders (17 days vs. 15 days). Quality of life index for patients at risk was 3.8 vs. 5.1 for more psychologically stable patients. CONCLUSIONS: Approximately 50% of patients undergoing surgery for malignant diseases develop severe psychotic disorders in the postoperative period. Preoperative psychological assessment seems to be extremely useful in providing adequate postoperative psychological support for individual patients.

[Characteristics of selected clinical features in BRCA1 mutation carriers affected with breast cancer undergoing preventive female genital tract surgeries]. / Charakterystyka wybranych aspektów klinicznych u kobiet, nosicielek mutacji genu BRCA1 poddanych operacjom profilaktycznym narzadu plciowego leczonych uprzednio z powodu raka piersi.

AIM: Evaluation of patient age and time of the prophylactic surgery as well as incidence of genital cancers and precancerous states observed in histopathology of the postoperative material from BRCA1 gene mutation carriers previously treated for breast cancer. MATERIAL AND METHODS: 206 carriers of one of the three most common BRCA1 gene mutations (5382insC, C61G and 4153delA) in the Polish population, who were offered the option of prophylactic salpingo-oophorectomy The study group comprised 85 patients with the diagnosis of breast cancer before gynecological preventive surgery The study group was further divided into two subgroups for more detailed assessment of the tested variables. The first subgroup included 67 patients with breast cancer (unilateral or bilateral synchronous). The second subgroup included 18 patients with bilateral metachronous (the second diagnosis of breast cancer was at least 12 months after the first breast cancer diagnosis). The control group consisted of 121 patients with no cancerous lesions before preventive gynecologic surgery The patients undergoing prophylactic treatment had no prior symptoms in female sexual organ and no changes in the diagnostic tests. RESULTS: The patients with a history of breast cancer underwent genetic testing and preventive surgery of the genital tract at a significantly later age than controls (respectively p = 0.0003, p = 0.0006). The patients with bilateral metachronous breast cancer underwent preventive surgery significantly earlier (p = 0.03). There was a trend indicating a 2.5 times higher risk of developing ovarian cancer among BRCA1 mutation carriers who had already been diagnosed and treated for breast cancer when compared to women without breast cancer diagnosis. The incidence of other genital cancers and precancerous states in BRCA1 gene mutation carriers with history of breast cancer was not statistically significant as compared to controls. Data on the clinical stage, morphological grade, histological type, age and type of pathology and the type of BRCA1 gene mutation did not show a statistically significant difference between the groups. CONCLUSIONS: Each patient diagnosed with breast cancer should be strongly recommended a genetic test to reduce adverse consequences resulting from postponing the test and, if applicable, the preventive operation until later in life. Preventive surgery should be considered especially in BRCA1 gene mutation carriers previously treated for breast cancer because of the increased risk of ovarian cancer

Extensive quantitative remodeling of the proteome between normal colon tissue and adenocarcinoma.

We report a proteomic analysis of microdissected material from formalin-fixed and paraffin-embedded colorectal cancer, quantifying > 7500 proteins between patient matched normal mucosa, primary carcinoma, and nodal metastases. Expression levels of 1808 proteins changed significantly between normal and cancer tissues, a much larger fraction than that reported in transcript-based studies. Tumor cells exhibit extensive alterations in the cell-surface and nuclear proteomes. Functionally similar changes in the proteome were observed comparing rapidly growing and differentiated CaCo-2 cells. In contrast, there was minimal proteomic remodeling between primary cancer and metastases, suggesting that no drastic proteome changes are necessary for the tumor to propagate in a different tissue context. Additionally, we introduce a new way to determine protein copy numbers per cell without protein standards. Copy numbers estimated in enterocytes and cancer cells are in good agreement with CaCo-2 and HeLa cells and with the literature data. Our proteomic data set furthermore allows mapping quantitative changes of functional protein classes, enabling novel insights into the biology of colon cancer.

[Features of pubescence in patients with pure gonadal dysgenesis in the course of a hormonally active tumor--case report]. / Cechy dojrzewania plciowego u pacjentek z czysta dysgenezja gonad w przebiegu hormonalnie czynnego guza--opis przypadków.

Germ cell tumors are the most frequent ovarian neoplasms among girls and young women under the age of 25. Female patients with gonadal dysgenesis are at higher risk of germ cell tumors. Two cases of women with pure gonadal dysgenesis were described. A hormonally active tumor secreting estrogens, caused the development of sexual features and genital tract bleeding what imitated premature puberty. It needs to be emphasized that the presence of sexual features does not exclude dysgenesis - a pathology that is connected with an increased risk of gonadal tumors--and that the ultrasound evaluation, during which the presence of follicles in gonads is evaluated, is essential.

Comparison of ultrafiltration units for proteomic and N-glycoproteomic analysis by the filter-aided sample preparation method.

The filter-aided sample preparation (FASP) method allows gel-free processing of biological samples solubilized with detergents for proteomic analysis by mass spectrometry. In FASP detergents are removed by ultrafiltration, and after protein digestion peptides are separated from undigested material. Here we compare the effectiveness of different filtration devices for analysis of proteomes and glycoproteomes. We show that Microcon and Vivacon filtration units with nominal molecular weight cutoffs of 30,000 and 50,000 (30 and 50k, respectively) are equally suitable for FASP, whereas Microcon 30k units are most appropriate for mapping of N-glycosylation sites. The use of filters with these relatively large cutoffs facilitates depletion of detergents.

[Isolated fallopian tube torsion in a teenager--a case report]. / Izolowany skret jajowodu u nastolatki--opis przypadku.

Adnexal torsion belongs to the group of urgent cases in gynecology Early diagnosis and management can prevent the loss of an ovary and the Fallopian tube. The case of the 14.5-year-old girl was described by the authors. The symptoms were moderate and caused diagnostics problems. During clinical assessment current literature knowledge, differentiation and treatment of the adnexa were taken into account.

Caenorhabditis elegans has a phosphoproteome atypical for metazoans that is enriched in developmental and sex determination proteins.

In eukaryotic species, signal transduction is often mediated by posttranslational modifications that can serve as regulatory switches. Although nematodes have usually been studied by genetic rather than biochemical methods, PTMs such as phosphorylation are thought to control all aspects of biological functions including sex determination and development. Here, we apply high accuracy mass spectrometry and comprehensive bioinformatic analysis to determine and characterize the in vivo Caenorhabditis elegans phosphoproteome for the first time. We detect nearly 7000 phosphorylation sites on 2400 proteins, which are disproportionately involved in development and sex determination. Interestingly, the worm phosphoproteome turns out to be very distinct from phosphoproteomes of other multicellular eukaryotes as judged by its phylogenetic conservation, kinase substrate motifs and site analysis by a support vector machine. This result agrees with the large proportion of worm specific kinases previously discovered by genome sequencing. Furthermore, our data show that the C. elegans specific dosage complex can be phosphorylated on most subunits, suggesting its regulation by kinases. Availability of the C. elegans phosphoproteome should add a novel dimension to functional data obtained by genetic screens in this organism.