Significance The moon provides highly reliable time information to organisms. Whereas sunlight is known to set daily animal timing systems, mechanistic insight into the impact of moonlight on such ...systems remains scarce. We establish that the marine bristleworm
times the precise hours of mass spawning by integrating lunar light information into a plastic daily timing system able to run with circadian (∼24 h) or circalunidian (∼24.8 h) periodicity. The correct interpretation of moonlight is mediated by the interplay of two light sensors: a cryptochrome and a melanopsin ortholog provide information on light valence and moonrise time, respectively. Besides its ecological relevance, our work provides a plausible explanation for long-standing observations of light intensity-dependent differences in circadian clock periods.
The circadian clock controls behavior and metabolism in various organisms. However, the exact timing and strength of rhythmic phenotypes can vary significantly between individuals of the same ...species. This is highly relevant for rhythmically complex marine environments where organismal rhythmic diversity likely permits the occupation of different microenvironments. When investigating circadian locomotor behavior of Platynereis dumerilii, a model system for marine molecular chronobiology, we found strain-specific, high variability between individual worms. The individual patterns were maintained for several weeks. A diel head transcriptome comparison of behaviorally rhythmic versus arrhythmic wild-type worms showed that 24-h cycling of core circadian clock transcripts is identical between both behavioral phenotypes. While behaviorally arrhythmic worms showed a similar total number of cycling transcripts compared to their behaviorally rhythmic counterparts, the annotation categories of their transcripts, however, differed substantially. Consistent with their locomotor phenotype, behaviorally rhythmic worms exhibit an enrichment of cycling transcripts related to neuronal/behavioral processes. In contrast, behaviorally arrhythmic worms showed significantly increased diel cycling for metabolism- and physiology-related transcripts. The prominent role of the neuropeptide pigment-dispersing factor (PDF) in Drosophila circadian behavior prompted us to test for a possible functional involvement of Platynereis pdf. Differing from its role in Drosophila, loss of pdf impacts overall activity levels but shows only indirect effects on rhythmicity. Our results show that individuals arrhythmic in a given process can show increased rhythmicity in others. Across the Platynereis population, rhythmic phenotypes exist as a continuum, with no distinct "boundaries" between rhythmicity and arrhythmicity. We suggest that such diel rhythm breadth is an important biodiversity resource enabling the species to quickly adapt to heterogeneous or changing marine environments. In times of massive sequencing, our work also emphasizes the importance of time series and functional tests.
Abstract
Access to newer, fast, and cheap sequencing techniques, particularly on the single-cell level, have made transcriptomic data of tissues or single cells accessible to many researchers. As a ...consequence, there is an increased need for in situ visualization of gene expression or encoded proteins to validate, localize, or help interpret such sequencing data, as well as put them in context with cellular proliferation. A particular challenge for labeling and imaging transcripts are complex tissues that are often opaque and/or pigmented, preventing easy visual inspection. Here, we introduce a versatile protocol that combines in situ hybridization chain reaction, immunohistochemistry, and proliferative cell labeling using 5-ethynyl-2′-deoxyuridine, and demonstrate its compatibility with tissue clearing. As a proof-of-concept, we show that our protocol allows for the parallel analysis of cell proliferation, gene expression, and protein localization in bristleworm heads and trunks.
The moon's monthly cycle synchronizes reproduction in countless marine organisms. The mass-spawning bristle worm Platynereis dumerilii uses an endogenous monthly oscillator set by full moon to phase ...reproduction to specific days. But how do organisms recognize specific moon phases? We uncover that the light receptor L-Cryptochrome (L-Cry) discriminates between different moonlight durations, as well as between sun- and moonlight. A biochemical characterization of purified L-Cry protein, exposed to naturalistic sun- or moonlight, reveals the formation of distinct sun- and moonlight states characterized by different photoreduction- and recovery kinetics of L-Cry's co-factor Flavin Adenine Dinucleotide. In Platynereis, L-Cry's sun- versus moonlight states correlate with distinct subcellular localizations, indicating different signaling. In contrast, r-Opsin1, the most abundant ocular opsin, is not required for monthly oscillator entrainment. Our work reveals a photo-ecological concept for natural light interpretation involving a "valence interpreter" that provides entraining photoreceptor(s) with light source and moon phase information.
The circadian clock controls behavior and metabolism in various organisms. However, the exact timing and strength of rhythmic phenotypes can vary significantly between individuals of the same ...species. This is highly relevant for rhythmically complex marine environments where organismal rhythmic diversity likely permits the occupation of different microenvironments. When investigating circadian locomotor behavior of Platynereis dumerilii, a model system for marine molecular chronobiology, we found strain-specific, high variability between individual worms. The individual patterns were maintained for several weeks. A diel head transcriptome comparison of behaviorally rhythmic versus arrhythmic wild-type worms showed that 24-h cycling of core circadian clock transcripts is identical between both behavioral phenotypes. While behaviorally arrhythmic worms showed a similar total number of cycling transcripts compared to their behaviorally rhythmic counterparts, the annotation categories of their transcripts, however, differed substantially. Consistent with their locomotor phenotype, behaviorally rhythmic worms exhibit an enrichment of cycling transcripts related to neuronal/behavioral processes. In contrast, behaviorally arrhythmic worms showed significantly increased diel cycling for metabolism- and physiology-related transcripts. The prominent role of the neuropeptide pigment-dispersing factor (PDF) in Drosophila circadian behavior prompted us to test for a possible functional involvement of Platynereis pdf. Differing from its role in Drosophila, loss of pdf impacts overall activity levels but shows only indirect effects on rhythmicity. Our results show that individuals arrhythmic in a given process can show increased rhythmicity in others. Across the Platynereis population, rhythmic phenotypes exist as a continuum, with no distinct "boundaries" between rhythmicity and arrhythmicity. We suggest that such diel rhythm breadth is an important biodiversity resource enabling the species to quickly adapt to heterogeneous or changing marine environments. In times of massive sequencing, our work also emphasizes the importance of time series and functional tests.
Based on the statistics the population in Bosnia and Herzegovina is getting older. In 2013 the average life span for women was 73.6 years and 68.1 for men. The chronic hemodialysis program is mainly ...reserved for elderly patients with high mortality risk. The most common cause of hemodialysis mortality relates to cardiovascular diseases (60.2%), regardless of frequent innovations and improvement of hemodialysis procedures.
was to determine the mortality rate by age groups with comments on the presence of non-traditional predictors (anemia, hypoalbuminemia, CRP, vascular access and PTH) in dialysis patients in the follow-up period of 36 months.
The study included all patients undergoing chronic hemodialysis treatment at the Clinic of Hemodialysis of the Clinical Center University of Sarajevo (CCUS).
Out of a total number of hemodialysis patients (n=232), the specific mortality rate in patients under 65 years of age was 16.8%, and 50.5% in patients over 65 years of age. According to the age groups the mortality rate in elderly patients is as follows: from 65 to 74 years (45.1%), from 75 to 84 years (55.0%), over ≥85 years (75.0%). The most frequent vascular access in patients under and above 65 is arteriovenous fistula (79.6% and 62.1 %), temporary hemodialysis catheter (11.7% and 43.8 %) and long-term hemodialysis catheter (8.8% and 4.2 %). In the age group under 65 years of age the temporary hemodialysis catheter is significantly and more frequently used in diseased patients in respect to survivors (34.8% vs. 7.0%) χ(2)(2)=15.769, p=0.001. Diseased patients from the age group over 65 had a significantly lower mean value of haemoglobin in blood (M=100.9±17.5 g/L) in respect to survivors (M=109.2±17.1)t(93)=2.339; p=0.021, lower mean value of albumin in blood (Me=32.0; IQR=29.0 do 35.0) in respect to survivors (Me=34.0; IQR=32.0 to 38.0) U=762.5; p=0.006, and higher mean value of CRP in blood (Me=19.3 mg/L; IQR=6.6 to 52.0) in respect to survivors (Me=7.8; IQR=4.0 to 16.7) U=773.5; p=0.008. Diseased patients belonging to the age group over 65 had lower mean value of PTH, but without statistical significance (p>0.05).
older age, temporary vascular access, anaemia and hypoalbuminemia are strong predictors of mortality in hemodialysis patients. Old age does not present contraindication for hemodialysis treatment, and treatment of terminal renal illness should not be abandoned.
Abstract
Background and Aims
The occurance of mid- and longterm uremic complications is related to the low clearance rate of middle and large molecule uremic toxins when hemodialysis (HD) alone is ...adopted. As the uremic toxins and their corresponding biological effects become increasingly clear, blood purification treatment that aims to remove these toxins, has developed from a stage of life-sustaining to improving the quality of life.
The objective of this study was to evaluated demographic, clinical and laboratory data in patients who underwent the combination of maintenance hemodialysis with hemoperfusion (HP) and in those who recieved HD alone and to investigate whether this combination could improve the clearance rate of middle and large molecule uremic toxins.
Method
A total of 26 patients, who underwent routine hemodialysis, were assessed in this study. Those patients were randomly divided into three groups: Group 1 (7 patients) received combined treatment of HD with HP biweekly (HD 2 times a week with HD+HP once a week), whereas Group 2 (10 patients) was given HD with high flux dialyzer and Group 3 (9 patients) was given HD with low flux dialyzer 3 times a week. This study was followed for 4 months. Before and after the observational period demographic and clinical data were taken from the medical history and blood samples were taken for hemoglobin (Hb), iron (Fe), total iron binding capacity (TIBC), albumin (Alb), calcium (Ca), phosphorus (P04) and parathyroid hormone (PTH).
Results
This study included 13 female and 13 male patients with a mean age of 41, 62 + 11.12 and a mean dialysis duration of 62, 78+53, 33 months. When it comes to baseline characteristics, patients of the group 3 were significantly older than patients in other groups (p=0.001). At the end of the four months observation period, the same difference according to age was noticed (p=0.01). Also, HD+HP group had significantly higher values of TIBC (p=0.006) and significantly lower serum levels of P04 (p=0.001). EPO doses were very similar in group 1 and 2, but in group 3 there were noticeably lower than in those two groups but without a significant difference. The serum levels of albumin were higher in group 3 compared to the other two groups but also without statistical difference. No statistical difference between groups after the follow up period was observed in terms of Hb, Fe, PTH, Ca, BMI, duration of dialysis treatment and vascular access. When groups are viewed individually, in the HD+HP group serum P04 levels were significantly lower after the 4 months off the follow up period than it was at the beginning (p=0.031) and also TIBC was significantly higher (p=0.018). In group 2 the values of TIBC were significantly lower after the follow up period than it was at the beginning (p=0.025). No significant difference was noticed in group 3 but serum PTH levels tends to decrease after 4 months compared to baseline measurement.
Conclusion
This combination treatment of HD with HP was superior to HD in reducing levels of phosphorus. These findings suggests a potential role of reducing the risk of cardiovascular events in this population especially when it is known that hyperphosphatemia has been pointed out as the primary culprit in the process of cardiovascular calcification. Also, patients who underwent the combined treatment showed higher values of TIBC but unfortunately no difference was noticed between Hb levels and EPO doses. These results eventually demonstrates their role in the improvement of renal disease anemia, which opens up the possibility of further research on a larger sample and over a longer period of time.
Abstract
Background and Aims
Some of the conditions which occur in maintenance hemodialysis (MHD) patients with a high incidence resulting in a decline in their quality of life, include malnutrition, ...renal osteodystrophy, refractory hypertension and chronic systemic inflammation. In developing countries, due to the low level of economic development, low-flux dialysis is the main means of extracorporeal blood purification therapy. But it can hardly remove the middle and large molecule uremic toxins and protein-bound toxins; as a result, the patients suffer from long-term complications and poor quality of life. In this study, we attempted to investigate whether the combination of maintenance hemodialysis (MHD) with hemoperfusion (HP) could improve the clearance rate of middle and large molecule uremic toxins so as to improve their uremic complications.
Method
A total of 54 patients, who underwent routine hemodialysis, were assessed in this study. Those patients were randomly divided into two groups: Group 1 (27 patients) received combined treatment of HD with hemoperfusion (HP) in this regimen: HD 2 times a week with HD+HP once a week two times in a row, then after two weeks, and afterwards once a month as a maintenance treatment. Group 2 (27 patients) was only undergoing maintenance HD 3 times a week. The clinical and laboratory properties of both groups were followed up for 18 months, whereas the primary outcomes included normal clinical data, high sensitive C-reactive protein (hsCRP), immunoreactive parathyroid hormone (iPTH), phosphorus (P04), calcium (Ca), albumin, iron (Fe), total iron binding capacity (TIBC), hemoglobin, Epo doses and types of hypertensive drugs.
Results
At the end of the 18-month observation, the serum concentration of albumin, P04, hsCRP, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lower with Group 1 than with Group 2 (p<0.05). Whereas, higher levels of iPTH were noticed in group 1, but when the laboratory and clinical data are analysed of the group 1 alone a statistically significant lower values after the observational period are noticed especially in the serum values of iPTH (p<0.05), P04 (p<0.001), CRP (p<0.011), SBP and DBP (p<0.05).
Conclusion
HD+HP was superior to HD in regularly eliminating middle and large molecule uremic toxins accumulated in the body which is mostly shown through reducing the values of iPTH and hsCRP. These findings suggest a potential role for HD+HP in the treatment of inflammation and renal osteodystrophy as well, because lowering these values of iPTH leads to a normalization of other minerals which is expected and therefore leads to a stabilization of this long-term uremic complications, which can improve the overall general condition of the MHD patient.
To determine the effect of a 16-week intradialytic exercise program consisting of 30 minutes of exercise during the first two hours of dialysis with three times a week frequency, on the quality of ...life (QoL), level of depression/anxiety and physical perfor- mance in hemodialysis (HD) patients.
The clinical, longitudinal, prospective study with one-group repeated measures design was conducted during a 16-week period. A convenience sample of 52 HD patients, who had been on HD for a minimum of 6 months, were included. QoL, level of depression and anxiety (questionnaires: SF-36, Back Depression Inventory (BDI) and Back Anxiety Inventory (BAI)) and physical performance (modifying Visual Analogue Scale (VAS) and Manual Muscle Testing (MMT)) were assessed at baseline and after 4-month exercise program.
The following scales of SF-36 questionnaire were improved after 16-week exercise program: role functioning/emotional (P=0.01 8), energy/fatigue (P = 0.002) and social functi- oning (P = 0.030). Level of depression and anxiety were significantly decreased in males (P = 0.007 and P = 0.022, respectively) and females (P = 0.001 and P = 0.000, respectively). VAS scale and MMT were significantly increased in males (P = 0.000 and P = 0.001, respectively) and females (P = 0.01 9 and P = 0.001, respectively) after 16-week exercise program.
Exercise program improves some aspects of QoL and physical performance, and decreases the level of depression and anxiety in HD patients.
Plasmapheresis is often used as a therapy in the treatment of thrombotic thrombocytopenic purpura (TTP). TTP is manifested in thrombotic microangiopathy, consumed thrombocytopenia, hemolytic anemia ...and acute kidney injury with HUS development, neurologic dysfunction, and fever.
we will present a case of a patient with acute kidney injury and refractory TTP at the beginning of hospitalization, subsequently manifested in secondary nephrotic syndrome. The patient was a female, 39 years of age, who as an emergency case was referred from the hospital in East Sarajevo to the Clinic of Endocrinology, Diabetes and Metabolism Disorders of the Clinical Center University of Sarajevo with suspected TTP. A few days before hospitalization she had a fever and vomiting, and therefore consulted her physician. She was hospitalized due to severe general condition, generalized edema, visible body hematomas, and diuresis amounting to 600 ml/12 hours. Laboratory results on admission were as follows: Leukocytes 19.5, Erythrocytes 3.23, Hemoglobin 103, Hematocrit 28.8%, Platelets 65.4 with few schistocytes and 2 reticulocytes, Sodium 140 mmol/L,, Potassium 4.5 mmol/L, Calcium 1.90 mmol/L, Glucose 7.9 mmol/L, Urea 37.5 mmol/L, Creatinine 366 umol/L,, Bilirubin 19.0 umol/L, Lactate dehydrogenase 1194 U /L. The patient was communicative, in cardiopulmonary sufficient state. Central venous catheter was placed in the right jugular vein and the first plasmapheresis was performed. During the hospitalization 38 plasmapheresis treatments with frozen plasma were performed, followed by three Rituximab treatment cycles. After the last plasmapheresis treatment a platelet count was 138. Also, parameters of the renal function were in their referent values. At the beginning of the treatment proteinuria was 19.6 g/24 hours urine. We were faced with a dilemma whether renal biopsy should be repeated in the future given that it might be the case of primary and not secondary nephrotic syndrome. Controlled proteinuria was 4.7g after plasmapheresis. The patient used only Prednisolone at a dose of 10 mg daily and although initially diagnosed with acute kidney injury she was not treated with dialysis.
early diagnosis and early start of plasmapheresis therapy is vital for treatment of patients with acute kidney injury and TTP (HUS). A small number of patients is refractory to plasmapheresis and introducing Rituximab and plasmapheresis treatment is recommended.
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