Could Capsule Endoscopy Be Useful in Detection of Suspected Small Bowel Bleeding and IBD-10 Years of Single Center Experience.

A retrospective study in patients who underwent video capsule endoscopy (VCE) between 2006 and 2016 was conducted in the Clinic for gastroenterology and Hepatology, University Clinical Center of Serbia. A total of 245 patients underwent VCE. In 198 patients the indication was obscure gastrointestinal bleeding (OGIB), with 92 patients having overt and the other 106 occult bleeding. The remaining 47 patients underwent VCE due to suspected small bowel (SB) disease (i.e., Von Hippel-Lindau syndrome, familial adenomatous polyposis, Peutz Jeghers syndrome, Crohn's disease, prolonged diarrhea, abdominal pain, congenital lymphangiectasia, protein-losing enteropathy, tumors, refractory celiac disease, etc.). VCE identified a source of bleeding in 38.9% of patients (in the obscure overt group in 48.9% of patients, and in the obscure occult group in 30.2% of patients). The most common findings were angiodysplasias, tumors, Meckel's diverticulum and Crohn's disease. In the smaller group of patients with an indication other than OGIB, 38.3% of patients had positive VCE findings. The most common indication is OGIB, and the best candidates are patients with overt bleeding; patients with IBD should be evaluated in this setting.

Neuroactive steroids in the neuroendocrine control of food intake, metabolism, and reproduction.

Neuroactive steroids are a type of steroid hormones produced within the nervous system or in peripheral glands and then transported to the brain to exert their neuromodulatory effects. Neuroactive steroids have pleiotropic effects, that include promoting myelination, neuroplasticity, and brain development. They also regulate important physiological functions, such as metabolism, feeding, reproduction, and stress response. The homoeostatic processes of metabolism and reproduction are closely linked and mutually dependent. Reproductive events, such as pregnancy, bring about significant changes in metabolism, and metabolic status may affect reproductive function in mammals. In females, the regulation of reproduction and energy balance is controlled by the fluctuations of oestradiol and progesterone throughout the menstrual cycle. Neurosteroids play a key role in the neuroendocrine control of reproduction. The synthesis of neuroestradiol and neuroprogesterone within the brain is a crucial process that facilitates the release of GnRH and LH, which in turn, regulate the transition from oestrogen-negative to oestrogen-positive feedback. In addition to their function in the reproductive system, oestrogen has a key role in the regulation of energy homoeostasis by acting at central and peripheral levels. The oestrogenic effects on body weight homoeostasis are primarily mediated by oestrogen receptors-α (ERα), which are abundantly expressed in multiple brain regions that are implicated in the regulation of food intake, basal metabolism, thermogenesis, and brown tissue distribution. The tight interplay between energy balance and reproductive physiology is facilitated by shared regulatory pathways, namely POMC, NPY and kisspeptin neurons, which are targets of oestrogen regulation and likely participate in different aspects of the joint control of energy balance and reproductive function. The aim of this review is to present a summary of the progress made in uncovering shared regulatory pathways that facilitate the tight coupling between energy balance and reproductive physiology, as well as their reciprocal interactions and the modulation induced by neurosteroids.

GSTM1 and GSTP1 Polymorphisms Affect Outcome in Colorectal Adenocarcinoma.

Background and Objectives: Despite improvements in screening programs, a large number of patients with colorectal cancer (CRC) are diagnosed in an advanced disease stage. Previous investigations imply that glutathione transferases (GSTs) might be associated with the development and progression of CRC. Moreover, the detoxification mechanism of oxaliplatin, which represents the first line of treatment for advanced CRC, is mediated via certain GSTs. The aim of this study was to evaluate the significance of certain GST genetic variants on CRC prognosis and the efficacy of oxaliplatin-based treatment. Materials and Methods: This prospective study included 523 patients diagnosed with CRC in the period between 2014 and 2016, at the Digestive Surgery Clinic, University Clinical Center of Serbia, Belgrade. Patients were followed for a median of 43.47 ± 17.01 months (minimum 1-63 months). Additionally, 109 patients with advanced disease, after surgical treatment, received FOLFOX6 treatment as a first-line therapy between 2014 and 2020. The Kaplan-Meier method was used to analyze cumulative survival, and the Cox proportional hazard regression model was used to study the effects of different GST genotypes on overall survival. Results: Individuals with the GSTM1-null genotype and the GSTP1 IleVal+ValVal (variant) genotype had significantly shorter survival when compared to referent genotypes (GSTM1-active and GSTP1 IleIle) (log-rank: p = 0.001). Moreover, individuals with the GSTM1-null genotype who received 5-FU-based treatment had statistically significantly shorter survival when compared to individuals with the GSTM1-active genotype (log-rank: p = 0.05). Conclusions: Both GSTM1-null and GSTP1 IleVal+ValVal (variant) genotypes are associated with significantly shorter survival in CRC patients. What is more, the GSTM1-null genotype is associated with shorter survival in patients receiving FOLOFOX6 treatment.

Multi- and Gray-Scale Thermal Lithography of Silk Fibroin as Water-Developable Resist for Micro and Nanofabrication.

Silk fibroin (SF) is a natural material with polymorphic structures that determine its water solubility and biodegradability, which can be altered by exposing it to heat. Here, a hybrid thermal lithography method combining scalable microscale laser-based patterning with nanoscale patterning based on thermal scanning probe lithography is developed. The latter enables in addition grayscale patterns to be made. The resolution limit of the writing in silk fibroin is studied by using a nanoscale heat source from a scanned nanoprobe. The heat thereby induces local water solubility change in the film, which can subsequently be developed in deionized water. Nanopatterns and grayscale patterns down to 50 nm lateral resolution are successfully written in the silk fibroin that behaves like a positive tone resist. The resulting patterned silk fibroin is then applied as a mask for dry etching of SiO2 to form a hard mask for further nano-processing. A very high selectivity of 42:1 between SiO2 and silk fibroin is obtained allowing for high-aspect ratio structure to be fabricated. The fabricated nanostructures have very low line edge roughness of 5 ± 2 nm. The results demonstrate the potential of silk fibroin as a water-soluble resist for hybrid thermal lithography and precise micro/nanofabrication.

Measurement of chromosomal instability and level of DNA damage in peripheral blood mononuclear cells of endometrial cancer patients.

Endometrial cancer is one of the most common invasive gynecologic malignancies in developed countries. The aim of this study was to evaluate chromosomal instability and level of DNA damage in peripheral blood mononuclear cells (PBMCs) of newly diagnosed endometrial cancer patients in relation to health status (diagnosis), age, histological grade of cancer, residence, smoking, number of pregnancies, miscarriages, and abortions. The analyzed sample consisted of 60 individuals, 30 endometrial cancer patients with an average age of 64.37 ±â€…7.08, and 30 healthy control women with an average age of 60.23 ±â€…11.55. Chromosomal instability was evaluated by the cytokinesis-block micronucleus (CBMN) assay, and the level of DNA damage by the single-cell gel electrophoresis (comet) assay in PBMCs. The average frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs) as well as nuclear buds (NBUDs) were significantly higher in cancer patients compared to controls (P < .0005). There was no difference in the nuclear division index (NDI) among the analyzed samples. The comet assay showed that the patients had a significantly increased genetic damage index (GDI) compared with controls (P < .0005). Using linear regression analysis, we found that health status (diagnosis) had the strongest influence on the MN frequency as well as GDI (P < .0005). Our results indicated that there is a high level of genetic damage in both the level of DNA and the level of chromosomes in the PBMCs of newly diagnosed patients with endometrial cancer, where the frequency and level of damage were significantly affected by health status, grade of cancer, residence, number of pregnancies, miscarriages, and abortions.

Oxidative stress and DNA damage in critically ill patients with sepsis.

The aim of our study was to assess the oxidative stress and inflammatory status in critically ill patients with sepsis as well as their relationship with the level of DNA damage. The study also evaluated the influence of all analyzed parameters on the outcome of the patients. The study included 27 critically ill patients with sepsis and 20 healthy subjects. Comet Assay was used for the measurement of the level of DNA damage, expressed as genetic damage index (GDI). Both oxidative stress parameters and the antioxidant parameters were obtained spectrophotometrically. The standard laboratory methods and the appropriate autoanalyzers were performed for determination the parameters of inflammation. A higher level of oxidative stress and more pronounced inflammation were found in the patients with sepsis compared to healthy subjects. The activity of the antioxidant enzymes was statistically declined in patients with sepsis, so that the most notable differences between two groups of participants were found for the activity of superoxide dismutase (SOD) (p = 0.004). Comet assay indicated that patients with sepsis had significantly higher GDI compared to healthy subjects (p < 0.001), which positively correlated with the concentration of superoxide anion radical (О2-) (r = 0.497, p = 0.010), and nitrites (NО2-) (r = 0.473, p = 0.015), as well with the concentration of C reactive protein (CRP) (r = 0.460, p = 0.041). Regression analysis confirmed that patients' age (p = 0.033), the level of О2- (p = 0.007), CRP concentration (p = 0.029) and GDI (p = 0.001) increased the risk of lethal outcome in critically ill patients with sepsis. In conclusion, critically ill patients with sepsis have a higher degree of oxidative stress and inflammation which contribute to a higher level of DNA damage. Consequently, above mentioned parameters, including patients' age, adversely affect the outcome of critically ill patients with sepsis.

Assessment of Three Breast Volume Measurement Techniques: Single Marking, MRI and Crisalix 3D Software®.

INTRODUCTION: Measuring breast volume is important to obtain satisfactory breast surgery results, and many techniques are used for this purpose. Thus, the aim of the present study was to compare 3 breast volume techniques: Pessoa's single marking technique, magnetic resonance imaging (MRI) and Crisalix 3D software®. METHODS: Fourteen patients indicated for mammoplasty were selected. Three breast volume measurement techniques were compared: Pessoa's single marking technique, MRI and Crisalix 3D software®. The volumes were tabulated and analyzed using R software. RESULTS: Average age was 30.93 ± 10.25 years. The breast volume was 1554.54 ± 512.54 cm3, as measured by the MRI technique (considered the gold standard), 1199.64 ± 403.13 cm3 using Crisalix 3D software® and 1518.04 ± 468.72 cm3 by Pessoa's single marking technique. Comparison between the Crisalix 3D software® and MRI techniques using the pairwise t test demonstrated a statistically significant difference (t = 4.3957, df = 27, p value = 0001543), but no significant difference between the single marking and MRI techniques (t = 1.3841, df = 27, p value = 0.1777). CONCLUSION: When compared to MRI, breast volume measurement using Pessoa's single marking technique showed no statistically significant difference between them. However, the Crisalix 3D® technique exhibited a difference in relation to MRI. Anthropometric measurements are useful in measuring breast volume because they are easy to obtain, practical and inexpensive, and should be part of a plastic surgeon's arsenal. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Putative application of Najas marina L. extracts as a source of bioactive compounds and their antioxidant, antimicrobial, antibiofilm, and genotoxic properties.

In this research paper, the total phenols (TP), flavonoids (TF), and tannins (TT) content in the acetone and ethyl acetate extracts of Najas marina L. and the identification and quantification of phenolic acids and flavonoids from the ethyl acetate extract were performed. Antioxidant, antimicrobial, and antibiofilm properties of the mentioned extracts were investigated in vitro. The genotoxic potential was analyzed in cultured human peripheral blood lymphocytes (PBL). The TP and TF content was higher in the ethyl acetate extract, dominated by quercetin (172.4 µg mg-1) and ferulic acid (22.74 µg mg-1), while the TT content was slightly higher in the acetone extract. Both extracts tested showed limited antioxidant effects compared to ascorbic acid. The strongest antibacterial activity was observed with Gram-positive bacteria, particularly Staphylococcus aureus (MIC and MMC at 0.31 mg ml-1) and S. aureus ATCC 25923 (MIC at <0.02 mg ml-1), while antifungal activity was limited. Both extracts tested showed better activity on preformed biofilms. Acetone extract had no genotoxic activity but showed significant genoprotective activity against mitomycin C-induced DNA damage in cultured PBLs. Results of our research demonstrate the potential for the development of plant-based antibacterial and biofilm agents.

Chronic Prostatitis/Chronic Pelvic Pain Syndrome Induces Depression-Like Behavior and Learning-Memory Impairment: A Possible Link with Decreased Hippocampal Neurogenesis and Astrocyte Activation.

Pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) remains unclear since it represents an interplay between immunological, endocrine, and neuropsychiatric factors. Patients suffering from CP/CPPS often develop mental health-related disorders such as anxiety, depression, or cognitive impairment. The aim of this study was to investigate depression-like behavior, learning, and memory processes in a rat model of CP/CPPS and to determine the alterations in hippocampal structure and function. Adult male Wistar albino rats (n = 6 in each group) from CP/CPPS (single intraprostatic injection of 3% λ-carrageenan, day 0) and Sham (0.9% NaCl) groups were subjected to pain threshold test (days 2, 3, and 7), depression-like behavior, and learning-memory tests (both on day 7). Decreased pain threshold in the scrotal region and histopathological presence of necrosis and inflammatory infiltrate in prostatic tissue confirmed the development of CP/CPPS. The forced swimming test revealed the depression-like behavior evident through increased floating time, while the modified elevated plus maze test revealed learning and memory impairment through prolonged transfer latency in the CP/CPPS group in comparison with Sham (p < 0.001 and p < 0.001, respectively). Biochemical analysis showed decreased serum levels of testosterone in CP/CPPS group vs. the Sham (p < 0.001). The CP/CPPS induced a significant upregulation of ICAM-1 in rat cortex (p < 0.05) and thalamus (p < 0.01) and increased GFAP expression in the hippocampal astrocytes (p < 0.01) vs. Sham, suggesting subsequent neuroinflammation and astrocytosis. Moreover, a significantly decreased number of DCX+ and Ki67+ neurons in the hippocampus was observed in the CP/CPPS group (p < 0.05) vs. Sham, indicating decreased neurogenesis and neuronal proliferation. Taken together, our data indicates that CP/CPPS induces depression-like behavior and cognitive declines that are at least partly mediated by neuroinflammation and decreased neurogenesis accompanied by astrocyte activation.

Environmental factors affecting pregnancy outcomes.

INTRODUCTION: Pregnancy represents a fragile period in the life of a woman, vulnerable to hazardous environmental substances which might affect maternal and fetal metabolism. The possible influence of environmental factors, including endocrine disrupting chemicals (EDCs), upon the mother and the fetus before and/or during pregnancy might be associated directly and/or indirectly to deleterious pregnancy outcomes. Because the existence of such associations would be, to our view, of major importance to the scientific community, their investigation is the scope of this critical review. METHODS: This critical review includes in vivo animal and human studies regarding the role of environmental factors, including EDCs, on pregnancy outcomes complying with the SANRA (a scale for the quality assessment of narrative review articles) questions for narrative reviews. Studies were identified by searching the MEDLINE (PubMed and PubMed Central), the Cochrane library and the Google Scholar databases till October 2022 with the combinations of the appropriate key words (detailed environmental factors including EDCs AND detailed negative pregnancy outcomes) as well as by scanning references from already included articles and relevant reviews manually. Because environmental factors and EDCs have been associated to epigenetic alterations, special care has been given to EDC-induced transgenerational effects on pregnancy outcomes. RESULTS: The existing evidence suggests positive associations between specific environmental factors and negative pregnancy outcomes such as ectopic pregnancies, pregnancy losses, gestational diabetes, hypertensive disorders of pregnancy, preterm births, birth defects, intrauterine growth restriction, and small or large for gestational age babies. CONCLUSION: Environmental factors and EDCs may have a catalytic effect on the course and the outcomes of pregnancy.

DNA damage in peripheral blood lymphocytes of severely ill COVID-19 patients in relation to inflammatory markers and parameters of hemostasis.

Bearing in the mind that a variety of agents can contribute to genome instability, including viral infections, the aim of this study was to analyze DNA damage in hospitalized COVID-19 patients and its relationship with certain laboratory parameters. The potential impact of applied therapy and chest X-rays on DNA damage was also estimated. The study population included 24 severely COVID-19 patients and 15 healthy control subjects. The level of DNA damage was measured as genetic damage index (GDI) by comet assay. The standard laboratory methods and certified enzymatic reagents for the appropriate autoanalyzers were performed for the determination of the biochemical and hematological parameters. COVID-19 patients had significantly higher level of DNA damage compared with control subjects. The absolute number of neutrophil leukocytes was statistically higher, while the absolute number of lymphocytes was statistically lower in COVID-19 patients than in healthy controls. The analysis of the relationship between DNA damage and laboratory parameters indicated that GDI was positively correlated with interleukin 6 (IL-6) concentration and negatively with platelet count in COVID-19 patients. The level of DNA damage was slightly higher in female patients, in whom it was demonstrated a positive correlation of GDI with C-reactive protein (CRP) and procalcitonin. Likewise, there was a negative relationship of GDI and platelet count, and positive relationship of GDI and activated partial thromboplastin time (aPTT) in female population. The applied therapy (antibiotics, corticosteroid, anticoagulant, and antiviral therapy) as well as chest X rays has been shown to have genotoxic potential. The level of DNA damage significantly corresponds to the inflammatory markers and parameters of hemostasis in COVID-19 patients. In conclusion, inflammation, smoking habit, applied therapy, and chest X rays contribute to a higher level of DNA damage in COVID-19 patients.

Orally administered fluorescent nanosized polystyrene particles affect cell viability, hormonal and inflammatory profile, and behavior in treated mice.

Commercially manufactured or generated through environmental degradation, microplastics (MPs) and nanoplastics (NPs) considerably contribute to environmental pollution. There is a knowledge gap in how exposure to MPs/NPs changes cellular function and affects animal and human health. Here, we demonstrate that after oral uptake, fluorescent polystyrene (PS) nanoparticles pass through the mouse digestive system, accumulate and aggregate in different organs, and induce functional changes in cells and organs. Using cochlear explant as a novel in vitro system, we confirmed the consequences of PS-MP/NP interaction with inner ear cells by detecting aggregates and hetero-aggregates of PS particles in hair cells. The testes of treated males accumulated MPs/NPs in the interstitial compartment surrounding the seminiferous tubules, which was associated with a statistically significant decrease in testosterone levels. Male mice showed increased secretion of interleukins (IL-12p35 and IL-23) by splenocytes while cyto- and genotoxicity tests indicated impaired cell viability and increased DNA damage in spleen tissue. Males also showed a broad range of anxiogenic responses to PS nanoparticles while hippocampal samples from treated females showed an increased expression of Bax and Nlrp3 genes, indicating a pro-apoptotic/proinflammatory effect of PS treatment. Taken together, induced PS effects are also gender-dependent, and therefore, strongly motivate future research to mitigate the deleterious effects of nanosized plastic particles.

Genetic Complementation of ATP Synthase Deficiency Due to Dysfunction of TMEM70 Assembly Factor in Rat.

Mutations of the TMEM70 gene disrupt the biogenesis of the ATP synthase and represent the most frequent cause of autosomal recessive encephalo-cardio-myopathy with neonatal onset. Patient tissues show isolated defects in the ATP synthase, leading to the impaired mitochondrial synthesis of ATP and insufficient energy provision. In the current study, we tested the efficiency of gene complementation by using a transgenic rescue approach in spontaneously hypertensive rats with the targeted Tmem70 gene (SHR-Tmem70ko/ko), which leads to embryonic lethality. We generated SHR-Tmem70ko/ko knockout rats expressing the Tmem70 wild-type transgene (SHR-Tmem70ko/ko,tg/tg) under the control of the EF-1α universal promoter. Transgenic rescue resulted in viable animals that showed the variable expression of the Tmem70 transgene across the range of tissues and only minor differences in terms of the growth parameters. The TMEM70 protein was restored to 16-49% of the controls in the liver and heart, which was sufficient for the full biochemical complementation of ATP synthase biogenesis as well as for mitochondrial energetic function in the liver. In the heart, we observed partial biochemical complementation, especially in SHR-Tmem70ko/ko,tg/0 hemizygotes. As a result, this led to a minor impairment in left ventricle function. Overall, the transgenic rescue of Tmem70 in SHR-Tmem70ko/ko knockout rats resulted in the efficient complementation of ATP synthase deficiency and thus in the successful genetic treatment of an otherwise fatal mitochondrial disorder.

Interplay between chronic hepatitis B and atherosclerosis: Innovative perspectives and theories.

Elaboration of carotid atherosclerosis in the setting of hepatitis B virus (HBV) infection should emphasize the significance of extrahepatic manifestations of the infection pathogenesis. Diverse processes comprise the pathoevolution of HBV infection, rendering it a multi-systemic disease in its essence. Our work not only exemplified atherosclerosis as an often-underestimated contributor to the severity of HBV infection but has also highlighted the bidirectional relationship between the two. Therefore, it is suggested that HBV-induced inflammation is one of the root causes of atherosclerosis, which in turn has a consequent effect on the severity of the chronic infection disease state, creating a vicious cycle. Additionally, we coupled prior data with the current concepts of HBV infection to postulate intriguing perspectives and theories.

Anemia as a Problem: GP Approach.

BACKGROUND: Anemia is a presentation of an underlying disease or deficiency. As stated by the WHO, anemia is defined as hemoglobin (Hb) levels <12.0 g/dL in women and <13.0 g/dL in men. This review of clinical practice aimed to determine the diagnostic approach to anemia in primary care patients. SUMMARY: Nutritional deficiencies, medications, chronic inflammatory conditions, malignancy, renal dysfunction, and bone marrow and inherent disorders contribute to anemia development. Anemia is classified and diagnosed by the values of hematological parameters, underlying pathological mechanism, and patient history. The diagnostic approach of anemia in primary care settings is focused on history, physical examination, laboratory findings including complete blood cell count, reticulocyte count, and peripheral smear examination, fecal occult blood test, and ultrasound findings. KEY MESSAGES: Anemia is the most common hematological disorder that represents a major health burden worldwide. Hb levels alter with gender, ethnicity, and physiological status. Anemia is often multifactorial. The evaluation of a patient with anemia in primary care includes clinical history, physical examination, and laboratory findings with fecal occult blood test and abdominal ultrasound. The wide variations in general practice in European countries are based on different health care systems but also knowledge of GPs that reflect educational and research policy.

Methanol extracts of Teucrium arduini L. and Teucrium flavum L. induce protective effect against mitomycin C in human lymphocytes in vitro.

The study was designed to evaluate antigenotoxic effect of methanol Teucrium arduini and Teucrium flavum extracts against mitomycin C (MMC)-induced chromosome and DNA damage in vitro. Cytokinesis-block micronucleus (CBMN) and comet assays were used to investigate effect of plant extracts in different concentrations (125, 250, 500 and 1000 µg/mL) on human peripheral blood lymphocytes (PBLs). The obtained results showed that the all tested concentrations of T. arduini and the highest concentration of T. flavum significantly reduced the MMC-induced micronucleus (MN) frequency in comparison to positive control (only MMC). There were significantly negative correlations between the extracts concentrations and MN frequencies (Pearson, r = -0.905, p = 0.0001 for T. arduini; r = -0.861, p = 0.0001 for T. flavum). The extracts of both plants further lowered the MMC-decreased nuclear division index (NDI) in a dose dependent-manner (Pearson, r = -0.837, p = 0.001 for T. arduini; r = -0.598, p = 0.040 for T. flavum), but significantly only in the highest concentration (1000 µg/mL). Comet assay showed that extracts reduced MMC-increased genetic damage index (GDI), significantly in the concentrations of 500 and 1000 µg/mL, in comparison with positive control. Based on our results, it can be concluded that methanol T. arduini and T. flavum extracts possess protective proapoptotic and antigenotoxic effect which is indication of their medicinal relevance and use in treatment.

Jaundice as a Diagnostic and Therapeutic Problem: A General Practitioner's Approach.

BACKGROUND: Jaundice is a common clinical finding in clinical practice of hepatologists and general practitioners. It occurs when serum bilirubin levels exceed 3 mg/dL. SUMMARY: In this review, we summarize the pathophysiological mechanism of jaundice, clinical approach to the patient with jaundice, and laboratory and imaging techniques. Clinical presentation of jaundice manifests through yellow skin and sclera coloration. Evaluation of every patient includes detailed medical history and examination. In the laboratory, evaluation of enzymes of hepatic inflammation as well as cholestatic enzymes with serum bilirubin must be included. Additional laboratory analysis and imaging modalities are needed in order to differentiate jaundice etiology. Moreover, imaging is available and needed in further evaluation, and treatment is dependent on the underlying cause. KEY MESSAGES: In this review, we will outline the pathophysiological mechanism of jaundice, clinical approach to the patient with jaundice, and diagnostic and treatment approach to these patients.

Abnormal Liver Blood Tests: Primary Care Approach.

BACKGROUND: According to recent epidemiological data, annual deaths due to liver disease have increased dramatically, while predictions show that trends will continue to rise in the upcoming years. SUMMARY: Abnormal liver blood tests are one of the most common challenges encountered in the primary care setting. The prevalence of mildly elevated transaminase levels is around 10-20% in the general population. The most common causes for the rising burden of liver disease are nonalcoholic fatty liver disease (NAFLD), alcohol-related liver disease (ARLD), and viral hepatitis. With improvements in the management of viral hepatitis over the last decades, the causes for the rising burden of liver disease are shifting toward ARLD and NAFLD. It is well-known that liver disease usually progresses silently for years or decades until the complications of cirrhosis occur. The majority of patients will not require referral to a specialist but will need further assessment in primary care. They should be evaluated for the etiology of liver disease irrespective of the duration of abnormal liver blood tests or unmarked clinical presentation. The evaluation should include a history of alcohol use, a history of medicines or herbal supplements, testing for viral hepatitis, and assessment for NAFLD, especially in obese patients and patients with type 2 diabetes. Abdominal ultrasound should be performed. Key Messages: The general practitioner may contribute significantly by identifying and screening patients at risk for chronic liver disease, as well as prioritize individuals with symptoms or signs of advanced liver disease to the specialist clinic.

Diarrhea as a Clinical Challenge: General Practitioner Approach.

BACKGROUND: Diarrhea is defined as the passage of loose stools and increase in stool frequency, weight, or volume. Diarrhea is an important health issue since it accounts for 2.5 million deaths in the world each year. SUMMARY: Diarrhea can be acute, persistent, or chronic. Acute diarrhea (AD) is usually infectious, caused by viruses, less frequently by bacteria and parasites. The majority of cases of AD are self-limiting and do not require diagnostic workup. The use of diagnostic tests in AD should be limited to patients with signs of severe dehydration, bloody stools, persistent fever and those suffering from immunodeficiencies using immunosuppressive therapy or to cases of suspected nosocomial infection. These patients should be referred to gastroenterologists or infectious disease specialists. Therapy in AD consists of early oral refeeding, antidiarrheal medications, antibiotics, and probiotics. Chronic diarrhea (CD) has diverse etiology. The majority of patients have self-limiting symptoms or functional gastrointestinal disorders. Patients with blood in stool, weight loss, clinical and laboratory signs of anemia, and palpable mass in the abdomen (red flag symptoms) need urgent gastroenterology referral. Therapy in CD is possible when the underlying cause of symptoms is identified. KEY MESSAGES: The general practitioner should identify high-risk patients with AD and/or red flag symptoms for urgent gastroenterology referral.

Relating environmental pressures to littoral biological water quality indicators in Western Balkan lakes: Can we fill the largest gaps?

Along six transects in each of six lakes across the Western Balkans, we collected data for three groups of littoral biological water quality indicators: epilithic diatoms, macrophytes, and benthic invertebrates. We assessed the relationships between them and three environmental pressures: nutrient load (eutrophication), hydro-morphological alteration of the shoreline, and water level variation, separating the effect of individual lakes and continuous explanatory variables. Lake water total phosphorus concentration (TP) showed substantial variation but was not related to any of the tested biological indicators, nor to any of the tested pressures. We suggest that this may be due to feedback processes such as P removal in the lake littoral zone. Instead, we found that a gradient in surrounding land-use towards increasing urbanization, and a land-use-based estimate of P run-off, served as a better descriptor of eutrophication. Overall, eutrophication and water level fluctuation were most important for explaining variation in the assessed indicators, whereas shoreline hydro-morphological alteration was less important. Diatom indicators were most responsive to all three pressures, whereas macrophyte biomass and species number responded only to water level fluctuation. The Trophic Diatom Index for Lakes (TDIL) was negatively related to urbanization and wave exposure. This indicates that it is a suitable indicator for pressures related to urbanization, although a confounding effect of wave exposure is possible. Invertebrate abundance responded strongly to eutrophication, but the indicator based on taxonomic composition (Average Score Per Taxon) did not. Our results suggest that our metrics can be applied in Western Balkan lakes, despite the high number of endemic species present in some of these lakes. We argue that local water management should focus on abating the causes of eutrophication and water level fluctuation, whilst preserving sufficient lengths of undeveloped shoreline to ensure good water quality in the long run.