The aim of this study was to assess how an admission to an acute palliative-supportive care unit (APSCU), may influence the therapeutic trajectory of advanced cancer patients.A consecutive sample of advanced cancer patients admitted to APCU was assessed. The following parameters were collected: patients demographics, including age, gender, primary diagnosis, marital status, and educational level, performance status and reasons for and kind of admission, data about care-givers, recent anticancer treatments, being on/off treatment or uncertain, the previous care setting, who proposed the admission to APSCU. Physical and psychological symptoms were evaluated at admission and at time of discharge. The use of opioids was also recorded. Hospital staying was also recorded. At time of discharge the parameters were recorded and a follow-up was performed one month after discharge.314 consecutive patients admitted to the APSCU were surveyed. Pain was the most frequent reason for admission. Changes of ESAS were highly significant, as well as the use of opioids and breakthrough pain medications (p <0.0005). A significant decrease of the number of “on therapy” patients was reported, and concomitantly a significant number of “off-therapy” patients increased. At one month follow-up, 38.9% patients were at home, 19.7% patients were receiving palliative home care, and 1.6% patients were in hospice. 68.5% of patients were still living.Data of this study suggest that the APSCU may have a relevant role for managing the therapeutic trajectory of advanced cancer patients, limiting the risk of futile and aggressive treatment while providing an appropriate care setting. Cancer patients may develop relevant symptoms during the course of disease. They spend more time in hospital wards for concurrent complications, uncontrolled symptoms, or to receive aggressive therapies, even in last weeks of life . Other tPalliative care is commonly provided at home, in hospice, or occasionally with mobile team in hospitals, when available. Regrettably, in most countries specialized palliative care is provided only for 2–3 weeks before death SimilarlyRecent evidence strongly suggests to start palliative care in other settings, other than traditional home care and hospice, to intercept cancer patients early in the course of disease, rather than limiting this intervention in the last weeks of life. An early referral to a palliative care team should be optimal to provide immediate symptom relief, treatment of drug-induce toxicities, education, and advice on the future therapeutic pathways –16. In tThe institutional review board at the University of Palermo approved the study and written patients’ informed consent was obtained. The study was performed in an APSCU, devoted to research and connected to the University of Palermo. This eight beds unit was established about 15 years ago in a small comprehensive cancer center. The characteristics of this unit have been described elsewhere .The goalA consecutive sample of advanced cancer patients who were admitted to an APSCU was prospectively assessed for a period of 10 months. Advanced cancer was considered as locally advanced, recurrent, or metastatic disease for solid cancers, and relapsed or refractory disease for hematologic tumors. All patients underwent comprehensive and continuous symptom assessment and management during their hospital stay at APSCU . At discPatients demographics, including age, gender, primary diagnosis, marital status, and educational level were collected. Performance status and reasons for admission were recorded, including pain or opioid-related problems, toxicity from chemotherapy, symptom control, re-evaluation, or end-of-life issues. The kind of admission was also characterized as unplanned or planned admission. Eventual re-admissions and their principal indications, and time from the previous admission, were recorded. Data regarding people living with the patients were gathered. A care giver was considered as a person who spent at least 4 hours/day with the patient. Patients’ and caregivers’ awareness of prognosis was assessed by semi-structured interviews . The following data were also recorded: chemotherapy in the last 30 days, or other anticancer treatments , on/off treatment or uncertain, that is when the need of oncologic treatment remained to be established and physicians delay taking a decision. It was also recorded the previous care setting, including home, hospital unit, day-hospital, or other hospitals, and who referred the patient to the unit, including home palliative care physicians, oncologists, other units, other hospitals, or general practitioner (GP).Physical and psychological symptoms were evaluated by Edmonton Symptom Assessment Scale (ESAS) at admission and at time of discharge (or the day before death). ESAS is a self-reported tool assessing the intensity of most common psychological and physical symptoms on a 0 to 10 numerical scale, rated on the average score in the previous 24-hour period. ESAS is a valid and reliable tool for assessing the overall symptom burden, sensible to changes produced by a treatment ,27.A scrStatistical analysis of quantitative and qualitative data, including descriptive statistics, was performed for all items. Continuous data were expressed as mean ± standard deviation (SD), unless otherwise specified. Frequency analysis was performed using the Pearson’s chi-square test and Fisher exact test, as needed. The univariate analysis of variance was used for parametric analysis; the paired samples Student's t-test was used to compare symptom intensity and opioid dosage, respectively, at the different intervals. Data were analyzed by IBM SPSS Software 22 version . All p-values were two-sided and p<0.05 was considered statistically significant.314 consecutive cancer patients admitted to the APSCU were surveyed. For the different parameters taken into consideration, data were missed for less than 10% of patients (range 0–20 patients). The characteristics of patients, stage of disease, kind of admission , information regarding relatives and the caregiver, educational level, indications for admission, active treatments in the last two weeks, and patients’ and caregivers’ awareness of disease are presented in Most admissions were planned, but a consistent number of patients admitted on emergency  or transferred from other hospital units. The mean hospital stay was 6.9 days (SD 6.3). Twelve patients (3.8%) died in the unit. A significant number of patients were assigned to home palliative care or hospice admission at time of discharge.Data regarding on how the patient was considered for treatment purposes , the setting where patients were previously cared, who referred the patient for admission, and clinical pathways suggested at discharge from the unit, are presented in At discharge a significant decrease of the number of “on therapy” patients was reported, and concomitantly the number of “off-therapy” patients increased. Regarding the possible relationships with the parameters considered, both epidemiological and sociocultural, younger patients, females, and diagnosis of breast cancer were more likely to be “on therapy” . Younger patients and patients who had a high Karnofsky status were more likely to be discharged home . No other significant relationships with clinical and sociocultural variables were found.ESAS at time of admission and at discharge (one day before death in patients who died) are presented in At admission, 197 patients were receiving a breakthrough pain medication . At discharge, 247 patients were receiving a breakthrough pain medication, principally represented by opioids . The difference was significant (p <0.0005).Seventy-five patients (23.9%) were readmitted, being 42 (13.4%), 15 (4.8%), and 9 (2.9%) patients previously admitted once, twice, and three times, respectively. Some patients had been admitted several times before (5–20 admissions) in a range of 4–24 months. The reasons for readmission were pain (72 patients) or/and opioid-related effects (11 patients), chemotherapy-related toxicity (11 patients), symptom control (34 patients), end of life care (2 patients). The mean number of days from the last admission was 71 days (SD 171).14 patients (4.5%) were lost at follow up (after 3 phone attempts). One patient or the relative (0.3%) refused the interview. Information regarding the oncologic treatment was available for 215 (68.5%) patients. 94 (29.9%) patients were continuing anticancer treatments, 83 (26.4%) were off-therapy, while in 38 (13.2%) patients the decision was uncertain.Information regarding the setting of care was unavailable for 100 (31.8%) patients. 122 (38.9%) patients were at home, 62 (19.7%) patients were receiving palliative home care, 5 (1.6%) patients were in hospice. For 25 (8%) patients information was imprecise.215 patients (68.5%) were still living, 59 patients (18.8%) died at home, two patients died in hospice (0.6%), two patients died in another hospital (0.6%), two patients (0.6%) died in an intensive care unit.The admission to a specialized APSCU resulted in a decrease in the number of patients continuing an anticancer treatment. This corresponds to a clear change in direction of the clinical trajectory. Moreover, the number of patients who were deemed to continue palliative care at home or in hospice increased, allowing them to be cared in a more appropriate setting. Of interest, hospital stay and mortality rate was extremely low, confirming the specificity of the APSCU. Finally, a dramatic improvement in symptom intensity as well toxicity from oncologic treatments was achieved in a short period of time. Taken together these data suggest the an APSCU admission is not only useful for symptom control or toxicities in complex clinical conditions, but also to allow an appropriate patients’ assessment according to more strict palliative care criteria and a multidisciplinary evaluation of the therapeutic options for individuals. Moreover, some patients may be more appropriately referred to territory resources including home palliative care or hospice. In other words, an APSCU may be a cross-road for advanced cancer patients, switching the lights for the right moment to turn their way.Many studies have reported the advantages of early palliative care when integrating oncologic treatment, advocating a better quality of life and a longer survival –31.HowevRelevant issues relative to the impact of a APSCU in an oncologic department have been recently raised –13,15. IAt present, APSCUs are available only in a some medical centres in USA ,15,20. bThere are some limitations regarding the interpretation of data of the present study. This was a single-centre experience and could not reproduced extensively. However, this model, together with those of other North American institutions which have largely provided their data . could bIn conclusion, data of this study suggests that the presence of APSCU in a comprehensive cancer center may have a relevant role for managing the therapeutic trajectory of advanced cancer patients, limiting the risk of futile and aggressive treatment while providing an appropriate care setting. Moreover, a broad and comprehensive intervention including the management of cancer–related complex symptoms and toxicities due to oncologic treatments, as well end of life care issues, may improve patients’ care with a short hospital stay and consequently reduced costs. The American Society of Clinical Oncology has progressively increased the visibility of palliative care and has developed education tools to improve oncologist skills in palliative care to facilitate the integration of both processes simultaneously, rather than in a sequential way, just confining palliative care at the end of life. These attitudes may also reduce aggressiveness of cancer care near the end of life .The appr


To propose a protocol for pulmonary angiography using 64-slice multidetectorcomputed tomography (64-MDCT) with 50 mL of iodinated contrast material, inan unselected patient population, as well as to evaluate vascularenhancement and image quality.2 to 41.8 kg/m2. Patients underwentpulmonary CT angiography in a 64-MDCT scanner, receiving 50 mL of iodinatedcontrast material via venous access at a rate of 4.5 mL/s. Bolus trackingwas applied in the superior vena cava. Two experienced radiologists assessedimage quality and vascular enhancement.We evaluated 29 patients (22-86 years of age). The body mass index rangedfrom 19.0 kg/mThe mean density was 382 Hounsfield units (HU) for the pulmonary trunk; 379and 377 HU for the right and left main pulmonary arteries, respectively; and346 and 364 HU for the right and left inferior pulmonary arteries,respectively. In all patients, subsegmental arteries were analyzed. Therewere streak artifacts from contrast material in the superior vena cava inall patients. However, those artifacts did not impair the imageanalysis.Our findings suggest that pulmonary angiography using 64-MDCT with 50 mL ofiodinated contrast can produce high quality images in unselected patientpopulations. In the beginning, when single-detector scans wereused, it was difficult to detect peripheral emboli and long scan times demanded large volumes ofcontrast material,5.Pulmonary computed tomography angiography (PCTA) has long been in use and has becomethe gold standard for the evaluation of patients with suspected pulmonaryembolism,7, there has been nosignificant reduction in the volume of iodinated contrast material required forpulmonary angiography in routine practice. In fact, there is extensive data in theliterature demonstrating that PCTA is more efficacious and better able to depictsmall vessels than are other diagnostic methods. Although authors have reported reducing the contrastvolume to 30-40 mL,10, their studies were conducted inselected populations under special conditions.Despite advances in multidetector computed tomography (MDCT) and increases in thespeed of acquisition of large volumes of data, weproposed a simple standard protocol with 50 mL of iodinated contrast material, in anunselected patient population, in which we tested vascular enhancement and imagequality.Following a more pragmatic approach, as discussed extensively in a recent studyconducted by Hartmann et al.2 to 41.8kg/m2 .Our study sample included 32 patients-25 females and 7 males, with a mean age of 53years - suspected of having acute or chronic pulmonarythromboembolism, who were referred to our outpatient clinic between September 2012and December 2013. The body mass index ranged from 19.0 kg/mAll patients underwent PCTA in a 64-slice MDCT (64-MDCT) scanner , with acquisition parameters of 1.25 mm digitalcollimation, 0.5 s tube rotation, pitch ratio of 1375:1, tube voltage of 100 kV, andautomatic tube current modulation . Because of technicalconstraints, a tube voltage of 120 kV was used in three patients: one who was obese(135 kg); and two who could not raise their arms over their heads.We injected 50 mL of iodinated contrast material  into an antecubital venous access, at apreferred rate of 4.5 mL/s. In four patients, the rate of injection was reduced to4.0 mL/s due to poor venous access. The total injection time ranged from 11.0 s (at4.5 mL/s) to 12.5 s (at 4.0 mL/s). In all patients, the injection of contrastmaterial was followed by the infusion of 30 mL of normal saline at the sameinjection rate. Bolus tracking was applied in the superior vena cava at the aorticarch level , with noTwo experienced radiologists assessed image quality, in terms of the capacity toidentify thromboembolism and signs of pulmonary hypertension, as well as enhancementof subsegmental pulmonary arteries and the presence of superior vena cava streakartifacts. As can be seen in In our study sample, the total scan time ranged from 2.2 to 2.8 s, with an mean of2.5 s.The overall mean arterial density, in Hounsfield units (HU), was 384 HU . Specifically, the mean ± standard deviation was 395 ± 99HU for the pulmonary trunk; 391 ± 94 HU and 390 ± 91 HU for the rightand left main pulmonary arteries, respectively; and 315 ± 96 HU and 378± 91 HU for the right and left inferior pulmonary arteries, respectively. Theoverall mean SNR and CNR were 28.7 and 25.2, respectively, for the right mainpulmonary arteries; 19.0 and 16.6, respectively, for the left main pulmonaryarteries; 23.1 and 20.2, respectively, for the right inferior pulmonary arteries;and 26.1 and 22.7, respectively, for the left inferior pulmonary arteries.Subsegmental arteries were analyzed in all patients.In 8 patients, we identified pulmonary thromboembolism, which involved major branchesin 3 and segmental to subsegmental arteries in 5. Signs of pulmonary hypertensionwere seen in 5 patients, all of whom showed enlarged pulmonary arteries, clearhypertrophy of the right ventricle being observed in only one case. However, amongthe patients with signs of pulmonary hypertension, only 2 showed thromboembolism inthe current PCTA.Streak artifacts from residual contrast material in the superior vena cava werepresent in all patients, although it did not impede image analysis of the pulmonaryarterial tree in any cases. The mean dose length product was 362.1 mGy* cm, and themean effective equivalent dose was 5.08 mSv.. In addition, it has been demonstrated that a large iodine loadis not warranted at a scan time less than 5 s, because that is much shorter than theduration of the contrast bolus.In the present study, the acquisition parameters applied yielded a mean scan time of2.5 s, with a mean delay of 6.6 s and total scan times just above 9 s. That is quitewell suited to an 11-s contrast column.It is almost common knowledge that the duration of the contrast injection, orcontrast column, should be approximately equal to the sum of the scan time and scandelay, as has previously been described. Despite the controversy in the literature about the risk andincidence of contrast-induced kidney injury and its outcome,13, some authors have identified a relationship betweenkidney injury and the volume of contrast material used. In addition, from a financial point of view,reducing the volume of contrast material used translates to a reduction in healthcare system costs.Reducing the volume of contrast material employed has several advantages, and thecurrent recommendation is to use the smallest volume and lowest dose of iodine thatwill yield a diagnostic result. However, severalauthors-18 have reported that, at same iodine delivery rate(IDR)-defined as iodine concentration multiplied by injection rate-there is no statisticaldifference among different iodine concentrations in terms of the contrastenhancement of the pulmonary arterial tree. In a recent study involving a porcinemodel, Behrendt et al. showedthat, at the same IDR, the greatest intravascular enhancement was achieved withmoderate iodine concentrations. In a previous study, Behrendt et al. had shown that, for chestimaging, better contrast enhancement was achieved with 300 mg I/mL than with 370 mgI/mL, at the same IDR. In the present study, we employed an IDR of 1.35 g I/s, witha total iodine dose of 15 g. In all patients, we achieved a arterial densitysuperior than the minimum attenuations of blood required to see all acute andchronic pulmonary venous thromboemboli , as calculatedby Wittram. Because the majorquality issue in CT angiography is intravascular enhancement and not tissueenhancement, the total dose of contrast is not an important factor. The major factorto consider is the acquisition time (scan time plus delay time) in relation to thecontrast bolus. The studies mentioned above have shown that a major index toconsider is the IDR, rather than the contrast iodine concentration or total iodinedose. In a study conducted by Wu et al., a total iodine dose of 9.6 g was injected in patientsreceiving a low dose (30 mL) of contrast material, with no reduction in imagequality, and the authors concluded that the volume of contrast can and should besignificantly reduced in carefully selected groups of patients. In the presentstudy, no patient selection would be made on any clinical basis. Therefore, we choseto use 50 mL of contrast at a 4.5 mL/s injection rate, given that, as previouslydiscussed, this combination would prove to be the most suitable in terms of thetechnical aspects. In addition, with no prior clinical selection, we figured thatsome problems related to cardiovascular conditions, such as cardiac insufficiency,could cause a loss of image quality at lower contrast volumes. We did not encounterthe inspiration artifact discussed in the literature,22, whichcould render a nondiagnostic result, in any of the cases evaluated here.A major point of discussion in the literature is which contrast material and iodineconcentration achieve the best results. Initially, contrast material with a higherconcentration of iodine was shown to produce better results,9,23,24, we used lowkilovoltage acquisition in our patients, with only three exceptions in which, due toclinical conditions, we used a tube voltage of 120 kV in order to avoidnondiagnostic results. We maintained the mean radiation dose at the suggestedlevels.In accordance with recent dataThe major limitation of our study is the absence of a control group for thecomparison of image quality, which limits the statistical analysis. Because the ideawas to assess the image quality obtained with the proposed protocol alone, we didnot work with a comparative control population. In fact, the main idea was to showthat good image quality can be achieved at a lower contrast volume, taking intoconsideration only the technical aspects discussed earlier, without patientselection. Other limitations of our study are related to the small size of thepatient population, as well as to its origin. Because ours is an outpatient clinic,we have not worked with patient populations that are clinically quitecomplicated.It seems that PCTA can be performed in a 64-MDCT scanner with 50 mL of iodinatedcontrast material in unselected patient populations, regardless of patientcharacteristics, and still produce images of high quality. Further clinical studies,involving larger patient samples in outpatient, emergency, and hospital settings,are needed in order to validate this protocol.


We sorted SNP pairs by distance and obtained a set of LD means  using bins of 5 Kb. We identified 15,246 segments of at least 1 Kb, among the 19 breeds, consisting of sets of at least 3 adjacent SNPs so that, for each SNP, r2 within its neighbors in a 100 Kb range, to the right side of that SNP, were all bigger than, or all smaller than, the corresponding expected mean, and their P-value were significant after a Benjamini-Hochberg multiple testing correction. In addition, to account just for homogeneously distributed regions we considered only SNPs having at least 15 SNP neighbors within 100 Kb. We defined such segments as structural variations. By grouping all variations across all animals in the sample we defined 9,146 regions, involving a total of 53,137 SNPs; representing the 6.40% (160.98 Mb) from the bovine genome. The identified structural variations covered 3,109 genes. Clustering analysis showed the relatedness of breeds given the geographic region in which they are evolving. In summary, we present an analysis of structural variations based on the deviation of the expected short range LD between SNPs in the bovine genome. With an intuitive and simple definition based only on SNPs data it was possible to discern closeness of breeds due to grouping by geographic region in which they are evolving.Genomic structural variations represent an important source of genetic variation in mammal genomes, thus, they are commonly related to phenotypic expressions. In this work, ∼770,000 single nucleotide polymorphism genotypes from 506 animals from 19 cattle breeds were analyzed. A simple LD-based structural variation was defined, and a genome-wide analysis was performed. After applying some quality control filters, for each breed and each chromosome we calculated the linkage disequilibrium ( It is well known that among human beings, 99.9% of DNA sequence is identical Kadri et al. (2012) Structural variations based on genotyping data have recently been the focus of interest, especially of the Copy Number Variation (CNV) type. The most used approach for detection of CNVs is based on two measures of signal intensity in each SNP: the Log R ratio , and the B Allele Frequency . The combination of Log ratio and B Allele Frequency is used to infer copy number changes in the genome Matukumalli et al (2011)Illumina, Inc, in collaboration with bovine researchers has developed the BovineHD panel of 777,962 SNPs genome-wide, making it the highest density panel in livestock. Taurus and Indicus subspecies of the Bos taurus species. We grouped them by purpose and geographical origin as follows: British meat breeds are the Angus, Hereford and Red Angus. European meat breeds are Charolais, Limousin, Piedmontese and Romagnola. Dairy British breeds are Guernsey and Jersey. European dairy breeds are Brown Swiss, Holstein and Norwegian Red. The Indicus group includes the Brahman, Nelore and Gir breeds. The African breeds are formed by the N'Dama and Sheko and lastly, the hybrid breeds (Taurus x Indicus) are formed by the Santa Gertrudis and BeefMaster.A set of 777,962 SNPs assayed by the BovineHD Genotyping BeadChip was provided by the International Bovine HapMap Consortium Quality control filters were applied in order to eliminate technology errors of the “no call” type, to eliminate all the genotypes that violated the Hardy-Weinberg equilibrium, and monomorphic markers . After these quality control filters we guarantee a global quality over all the samples and we worked, in average between the 19 breeds, with a total of 523,651 markers which represents 67.31% of the initial information , is defined by a Markov chain, and it models how the haplotype pair copied from the reference panel changes during the sequence due to a recombination map (p) defined throughout all the genome.P, generates the observed variation of the genotype vectors regarding to the copied haplotypes of the reference panel through a mutation rate (θ ) 2r) represented as:p1 and p2 are the minor and major allele frequencies in the SNP1 respectively, q1 and q2 are the minor and major allele frequencies in the SNP2 respectively, and p11 corresponds to the frequency observed between both minor alleles in the same individual throughout the whole population. In addition, a sample size correction was applied to all computed 2r values using the following equation:n represents the number of haplotypes in the sample The LD coefficient selected for this study was the squared correlation coefficient between pairs of SNPs (r2) of short range (≤100 Kb), sorting SNP pairs by distance, and obtaining the means using bins of 5 Kb. Then we interrogate SNP by SNP looking for segments of at least 1 Kb, consisting of a set of at least 3 adjacent SNPs so that, for each SNP, r2 within its neighbors in a 100 Kb range, to the right side of that SNP, are all bigger than, or all smaller than, the corresponding expected means, and their P-values from a t-test for equality of means are significant after a Benjamini-Hochberg multiple testing correction. In addition, to account just for homogeneously distributed regions consider only SNPs having at least 15 SNP neighbors within 100 Kb.We define a LD-based Structural Variation as follows: first, for each breed and each chromosome we obtain a set of LD means, called expected means, calculating the linkage disequilibrium p, for each i between 1 and m , then, starting from the largest P-value Pm)( with 0.05 x i/m. Continue as long as Pi)(>0.05 x i/m. Let k be the first time when Pk) and look for differentiation between cattle subgroups. We used R software to perform this analysis. The central idea of PCA is to reduce the dimensionality of a data set which consists of a large number of interrelated variables, while retaining as much as possible of the variation present in the data set. This is achieved by transforming a new set of variables, the principal components (PCs), which are uncorrelated, and which are ordered so that the first few retain most of the variation present in all the original variables Formally, PCA is defined as an orthogonal linear transformation that transforms the data to a new coordinate system such that the greatest variance by any projection of the data comes to lie on the first coordinate , the second greatest variance on the second coordinate, and so on. PCA is theoretically the optimum transform for a given data in least square terms. The procedure for obtaining PCAs can be summarized as follows:TX of n dimensions, T = TX, whose mean vector M and covariance C are described by:Given a vector 1, λ2, …, λ3, and the eigenvectors 1P, 2P, …, dP; arrange them according to their magnitude.Calculate the eigenvalues λd eigenvectors to represent the n variables, d<n. Then the 1P, 2P, …, dP are called the principal components.Select The filtered data set included an average of 523,651 genotypes per breed, among the 29 autosomal chromosomes in 506 animals from 19 breeds . The Brahman may have a higher rate of polymorphism than the remaining indicine breeds because that breed was established by importing primarily bulls and backcrossing to taurine derived females. The Bos taurus taurus breeds were generally moderately variable with an average of 83% of polymorphic SNPs. The Bos taurus indicus breeds show the lowest average polymorphic SNPs with 81%. The lone tropically adapted r2. Values of LD were corrected for sample size using the equation described by Villa-Angulo et al. (2009) Bos taurus indicus breeds: Brahman, Gir, and Nelore, with 0.367, 0.395, and 0.401, respectively, while the breeds with the highest average of LD were Hereford, Jersey, and N'Dama, with 0.639, 0.630, and, 0.616, respectively. On the other hand, in large distances (100 Kb), the breeds with the lowest averages of LD were Piedmontese, Sheko, and Charolais, with 0.085, 0.104, and 0.105, respectively, while the breeds with the highest average of LD were Hereford, Jersey, and Brown Swiss, with 0.222, 0.201, and 0.177, respectively. , using the same samples, the trends obtained are quite similar, even when only high density SNPs regions in chromosomes 6, 14, and 25 were considered r2 values are smaller than the expected means, and as the previous example they were declared significant after correction. At the bottom, an example presumed to contain no structural variation because LD for some of the SNP pairs alternate from being bigger than to smaller than their expected LD mean .For each breed and each chromosome we obtained a set of LD means (expected means) using bins of 5 Kb. Then, for each SNP we calculated LD with each polymorphic SNP within 100 Kb to the right of that SNP. Putative structural variations were defined where all LD measures were bigger than, or all smaller than, their corresponding expected means, for all SNP pairs within 100 Kb region for at least 3 adjacent polymorphic SNPs. Using the above definition we scanned all autosomal chromosomes for each breed. Bos taurus group. While, Nelore, BeefMaster, Sheko, Gir, Brahman and Santa Gertrudis were the breeds with the smallest number of SNPs falling in SVs, with 1560, 1670, 1733, 1756, 1871, and 1992 respectively. All these breeds, are from Bos indicus and composite groups. The average number of SNPs falling in SVs across all breeds was 5531.78. The breeds with the highest average of SNPs per SV were Hereford, Jersey, Red Angus, Guernsey, Brown Swiss, Angus, and Norwegian Red, all from the Bos taurus group, while the breeds with the smallest average of SNPs per SV were Sheko, Brahman, Nelore, BeefMaster, Gir, and Santa Gertrudis, from the Bos indicus and composite groups.From Bos taurus group. Asian breeds resulted with the smallest SV, in SNPs quantity.The 5 breeds with SVs containing the largest number of SNPs : Gir, Brahman and Nelore resulted with positive loads if observed from PC1 and they are displayed really close. In the same way composite breeds: Santa Gertrudis and BeefMaster resulted with positive loads (for PC1), and they are displayed really close too. Some British breeds: Angus, Red Angus, Hereford, Jersey, and Guernsey, and European breeds: Brown Swiss, Norwegian Red and Holstein, all resulted with negative loads, when observed from PC1 axis, and appear relatively separated from the other groups. On the other hand, the two breeds from the African group, N'Dama and Sheko, appear relatively far from each other. It is explained from the fact that Sheko is a Taurus Indicus breed while N'Dama is Taurus Taurus.In order to investigate the closeness in variability among breeds given the amount of identified structural variations; for each breed we constructed a vector of 29 fields, where each field contained the number of SVs in a chromosome. Principal Component Analysis In support of our results that show a clear regional differentiation between breed groups given the quantity of variations, we analyzed the result of a study that was carried out in the “Y” chromosome of European domestic cattle Jiang et al. (2013) Cicconardi et al. (2013) Hou et al.  Liu et al. (2010) Jiang et al (2013) we found 113 overlaps of 358 CNVRs, representing the 31.56%. For Cicconardi et al. (2013), we found 311 overlapping regions, representing the 78.73% of the 395 reported regions. For Hou et al , we found 178, 505 and 267 overlaps of 462, 3438 and 672 variations reported, representing the 38.52%, 14.68% and 39.73% of overlapping regions respectively. Finally for Liu et al. (2010), we considered just the eleven breeds both studies have in common. We found 36 overlapping regions, representing the 25.35% of the 142 reported regions.Given that we found 6.4% of the genome involved with SV, we intuitively suggested overlapping with other types of variations already reported by other groups. Then, we analyzed how much overlap existed between our findings and structural variations from the CNV type. We compared the number, position, and length of structural variations. Next, we searched in NCBI The last analysis was to look within our defined structural variations for regions that were consistent in all 19 breeds. We did not found common regions among all breeds. However, there are 2 regions where 17 breeds coincided, 2 regions where 15 breeds coincided, 2 regions where 14 breeds coincided, 3 regions where 13 breeds coincided and 13 regions where 12 breeds coincided, even when they do not coincide with the total length, at least they share one segment declared as variation.  from the bovine genome. The number of genes covered by these variations was 3,109. From a comparison of overlapping with variations of the CNV type previously reported we found overlapping ranging from 14.68% to 78.73%,An analysis of differentiation based on the number of structural variations genome-wide showed great difference between some breeds and reveled closeness of groups given the geographic region in which they are evolving. Finally, even when there is overlapping of LD-based Structural Variations with CNVs, they capture different genomic variation patterns, and further studies would be necessary in order to elucidate their association to disease and other phenotypic traits.Figure S1Figures S1–S7: MAF Distribution. Average proportions of SNPs of various frequencies per breed and per groups.(DOCX)Click here for additional data file.File S1Table S1. Breeds and number of animals in the sample.(XLSX)Click here for additional data file.File S2Table S2. Final summary of markers for our study.(XLSX)Click here for additional data file.File S3Table S3. Mean and Median MAF average of 19 breeds.(XLSX)Click here for additional data file.File S4Table S4. Average values obtained by 2r for all breeds (LD decay).(XLSX)Click here for additional data file.File S5Table S5. Variants per Chromosome and average per Megabase.(XLSX)Click here for additional data file.File S6Table S6A. Type, name and description of genes found in this study. Table S6B: Number of genes per breeds. Table S6C: Number of genes per chromosome.(XLSX)Click here for additional data file.File S7Table S7. Variation Structural Regions.(XLSX)Click here for additional data file.


Identification of cytogenetic abnormalities plays an important role in the diagnosis and prognosis of leukemias. Isolated trisomy 6 is a rare abnormality, the prognostic significance of which is not well established. We report one case of acute myeloid leukemia (AML-M5 variant) with trisomy 6 as the sole cytogenetic abnormality. Previously, trisomy 6 has been reported in aplastic anemia, myelodysplastic syndrome, and AML, usually associated with hypocellular marrow. However, our patient had a very short history and hypercellular marrow infiltrated with blasts. We report this case due to the rarity of the condition. More studies are required to ascertain the role of trisomy 6 in the development of leukemia as well as in prognosis. Identification of cytogenetic abnormalities plays an important role in the diagnosis and prognosis of leukemias. However, apart from recurrent cytogenetic abnormalities, the role of other rare abnormalities is not well known. Numerical aberrations as the only karyotypic anomalies, including single or multiple losses or gains, are found in approximately 15% of all cytogenetically abnormal hematological malignancies . Here weA 21-year-old female reported to the Department of Hematology, All India Institute of Medical Sciences, New Delhi, India, with complaints of generalized weakness and fatigue of 2 weeks in duration. She was found to be pale and had received packed red cell transfusions during this period. On general examination she had anemia, fever, and sternal tenderness. There was no lymphadenopathy or bleeding manifestations. On systemic examination, she had hepatomegaly 6 cm below the costal margin, but the spleen was not palpable.Complete blood count revealed a hemoglobin level of 5.4 g%, total leucocyte count of 56.3x103/µL, and platelet count of 85x103/µL. Peripheral smear showed 25% blasts of monocytoid morphology. Bone marrow aspirates and touch preparation revealed hypercellular marrow filled with monoblasts and promonocytes. On cytochemistry, blasts were positive for myeloperoxidase, nonspecific esterase, and Sudan Black B and negative for periodic acid-Schiff and acid phosphatase. Bone marrow biopsy showed 100% cellularity with diffuse replacement by blasts.Immunophenotyping was performed by 6-color flow cytometry using a BD FACSCanto . Gated blast populations of cells were positive for CD13, CD33, CD34, HLA-DR, cMPO, CD64, and CD10. Bone marrow morphology, cytochemistry, and immunophenotyping were consistent with the diagnosis of AML-M5.Cytogenetic analysis was performed on a short-term unstimulated bone marrow culture with and without colcemid using standard cytogenetic techniques . G-bandeShe was started on 7+3 induction with cytarabine at a dose of 100 mg/m2/day as a continuous infusion over 24 h for 7 days and daunorubicin at 60 mg/m2/day as a short infusion for 3 days. After the first induction, bone marrow on day 14 revealed persistence of blasts (34%). Hence, she was given a second induction with mitoxantrone and high-dose cytarabine (HAM). After treatment with HAM, the patient developed septicemia with cardiac dysfunction and bilateral fungal pneumonia, for which she was treated appropriately. After blood counts recovered, bone marrow testing was repeated and she was found to be in remission. She then received 2 more cycles of high-dose cytarabine as postremission therapy. She recovered uneventfully, and is presently being followed up with on a regular basis. Counselling regarding HLA-typing with her sibling and possible need for bone marrow transplantation was given, but this was deferred due to monetary constraints. Informed consent was obtained.Gains and losses of whole chromosomes are frequently found in hematological malignancies, either identified as solitary abnormalities at diagnosis or superimposed on other abnormalities in later stages of the disease . TrisomyA literature search reveals that only 14 cases of AML and 5 cases of myelodysplastic syndrome (MDS) have been reported with isolated trisomy 6. It has been seen in patients with aplastic anemia (AA), MDS, and AML, and is very rarely seen in childhood mixed-lineage leukemia, lymphoblastic transformation of chronic myeloid leukemia, and chronic myeloproliferative disorders. In most of the published cases, patients usually had hypocellular marrow with erythroid dysplasia or they proceeded from AA to AML . It has In our case, blasts were positive for CD34 and HLA-DR, similar to previous cases, which indicates the primitive nature of the blasts . ResponsDue to the limited number of cases reported in the literature, the role of trisomy 6 as the sole cytogenetic abnormality is not clear, but from the data available, it is likely that this clonal cytogenetic abnormality is associated with the primitive nature of blasts and poor response to treatment ,9. More Isolated trisomy 6, although found in many hematological disorders, is rare as a sole abnormality in patients with AML. Although it has been reported more commonly in AA and MDS, it can also be observed in patients with de novo AML. The prognostic significance of this abnormality is not well established at present.


Kaposi sarcoma is a tumour caused by human herpes virus 8, also known as Kaposi sarcoma-associated herpes virus. It usually affects the skin and oral mucosa; however, it can also sometimes affect the lungs, the liver, the stomach, the bowel, and lymph nodes. Several body sites may be affected simultaneously. The involvement of the tonsils is rare. We described an isolated localization of Kaposi's sarcoma of the right tonsil in a HIV-positive patient. HIV/AIDS represents an important clinical and public health issue worldwide. The estimated HIV/AIDS prevalence in 2012 was 35,300,000 worldwide in 2012 . In case of severe immunodeficiency, the probability of occurrence of several opportunistic disorders  can increase. Kaposi's sarcoma (KS) is a frequently reported neoplasia in HIV-positives; it is caused by human herpes virus 8 (HHV-8), also known as KS-associated herpes virus (KSHV) , stomachHere, we present a case of KS of the right tonsil in a HIV-positive patient, surgically treated and exposed to antiretroviral drugs.A 42-year-old man was admitted to the Emergency Department of the S.Francesco Hospital, Nuoro, Italy, because of a painless swelling, moderate bleeding, located in his right tonsil. He referred to its occurrence without any other relevant symptoms 1 month ahead.Oral examination shows a purple swelling  in the uThe histopathological analysis identified a KS Figures , and 5. His past medical history includes a borderline hypertension treated with a diet approach.μL and >100,000/mL, respectively (CDC stage C2). On the basis of the TIS classification (μL) and the level of viral load decreased gradually .After surgical treatment his CD4 lymphocyte count and HIV viral load were 207 cells/fication  17], he, heμL anμL.After 15 months since KS diagnosis the patient is alive and KS-free with a CD4 cell count of 342 cells/KS is an important opportunistic disease, which frequently occurs in HIV-positive patients characterized by a severe immunodeficiency. The KS incidence in the general population is 1 case per 100,000 inhabitants , whereasThe AIDS-related KS lesions, affecting the skin of the upper trunk and face , 3, and The therapeutic choice and the following prognosis are extremely variable, depending on the stage and the KS type.The AIDS Clinical Trials Group Oncology Committee published criteria for the evaluation of the epidemic KS . The staThis classification includes two group of patients: “Good risk category (T0I0S0)” and “Poor risk category (T1I1S1).” The patient that we described was classified as T0I0S0.KS can be treated with radiotherapy, chemotherapy, biologic agent as interferon alfa, and surgery: in HIV-positive patients it can be managed with HAART or with a combination of this therapeutic approach.HAART seems to be indispensable in the treatment of the AIDS-related KS, alone or in combination with systemic or/and local therapy . HAART cRadiotherapy is an effective palliative treatment reducing pain, bleeding, and oedema. Cutaneous KS is highly radiosensitive as described by Donato et al. in a group of 38 AIDS-associated KS lesions . They shChemotherapy (CHT) can be local  or systemic (intravenous). Local CHT, based on bleomycin, cisplatin, and vinblastine, can represent an alternative therapy for limited cutaneous KS with complete or partial response rates (range: 60–92%) , 26. SysInterferon alfa, showing immunomodulatory, antiviral, and antiangiogenetic actions, can be used alone or in combination with HAART. It can favour a remission of the KS lesions in 20 to 60% of the exposed cases , 29. ThePatients with clinical progression despite CHT and/or HAART can be currently approached with the so-called “Target Therapy”  and thalidomide, metalloproteinases (MMPs), and cytokine signalling pathway inhibitors) . MMPs arBiopsy of the lesion is deemed mandatory for the histological diagnosis, but in cases of isolated cutaneous and visceral KS surgical excision is recommended in association with HAART, as showed in our review , 14, 16.The patient we managed underwent tonsillectomy and HAART with complete eradication of the tumours.Isolated KS of the tonsil is very rare and can simulate benign or malignant lesions, such as pyogenic granuloma, carcinomas, and sarcomas. Histological diagnosis, HIV testing and CT scans of the chest and abdomen, and an endoscopy of the upper gastrointestinal tract can be helpful for an appropriate stage of the tumours and, consecutively, to plan a better therapeutic approach.


Current reports on movement disorder adverse effects of acetylcholinesterase inhibitors only include extrapyramidal symptoms and myoclonus.Here is a case of an 81-year-old female Filipino with dementia who presented with first-onset generalized choreiform movements.The etiology of the clinical finding of dyskinesia was investigated through laboratories, neuroimaging, and electroencephalogram, all of which yielded negative results. Review of her medications included the rivastigmine (Exelon) patch, which had just been increased to 13.3 mg/24-hour-dose 3 months prior. With all other possible causes excluded, a trial discontinuation of rivastigmine, showed decreased frequency of the dyskinesia 48 hours after, with complete resolution after 6 days, and no recurrence since then.This case thus presents a probable association or causality between the choreiform movement and rivastigmine at 13.3 mg/24-hour-dose patch because of clear temporal proximity, lack of alternative explanations, and a reversal of the dyskinesia upon medicament discontinuation. Apart from the common gastrointestinal symptoms, neurologic manifestations including headache, dizziness, vertigo, syncope, change in sensorium, confusion, irritability, agitation, hallucinations, seizure, and extrapyramidal symptoms may also occur as seen in 7 of the 12 studies reviewed.3 Only the study by Sobow and Kloszewska2 showed consequent motor dysfunction termed as extrapyramidal symptoms however its phenomenology was not described. These were seen in 2 patients under the donepezil (5–10 mg/day) group and 3 patients under the rivastigmine (6–12 mg/day) group.Majority of research comparing cholinesterase inhibitors show no significant difference in drug efficacy but instead in the incidence of adverse effects. In 2006, Lockhart et alThis case report is documentation of an uncommon adverse event related to rivastigmine (Exelon) 13.3 mg/24-hour patch in the form of choreiform movement.This is a case of an 81-year-old female, Filipino, who presented with involuntary movements. Diagnosed with severe dementia of the Alzheimer's type, she is dependent in all activities of daily living, including mobility out of bed. She is able to respond to others with subtle facial expressions but has no comprehensible verbal output. She has hypertension, cardiac arrhythmia, coronary artery disease, and deep venous thrombosis. She has a cardiac pacemaker, which was placed due to sick sinus syndrome. Her maintenance medications included amiodarone, metoprolol, rivaroxaban, and patch rivastigmine. Quetiapine was sparingly administered at half to one tablet of 25 mg, as necessary for insomnia and restlessness.In particular, the patient has been on rivastigmine transdermal patch since April 2009 at a dose of 4.6 mg/24 hours, and which was increased to 9.5 mg/24 hours in August 2009. In these doses of rivastigmine, no note of adverse events occurred. Because of the progression of her dementia symptoms, the rivastigmine dose was increased to 13.3 mg/24 hours in March 2014.The patient was apparently well until June 13, 2014, when she developed involuntary movements of the left lower extremity. This was described as fluid, jerky and at times flinging in character, with similar observations later involving her left upper extremity and the right extremities as well. She remained alert and responsive, and was immediately brought to their local hospital  scan was done which showed no new noticeable lesions  before applying the new one, while ensuring a daily change of patch application at recommended sites. Vomiting did not occur, and neither was the patient administered metoclopramide.Levetiracetam was discontinued as the movement as described was not seen to be a form of seizure. A trial discontinuation of the transdermal patch was done on June 15, 2014. A marked reduction of frequency of the choreiform movement was seen 2 days after, and a complete resolution was seen after 6 days. An 1-time rechallenge with the same patch dose was tried, which again showed reemergence of the choreiform movements. Thus, rivastigmine 13.3 mg/24 hours/patch was discontinued, and the family was not keen on introducing the patch again, even at previous lower doses. Choreiform movements did not recur, up until this present report.The reversal of the choreiform movements after discontinuation of rivastigmine, and its recurrence on the same drug challenge, shows a possible causality worth investigating. Notably, rivastigmine was the only drug that had a dose augmentation, while the other medications on board were kept at maintained doses. Investigation of the etiology of the choreiform movement was as previously mentioned limited by the cardiac pacemaker not allowing for more sophisticated neuroimaging.4 The patient who has been chronically maintained on amiodarone had no history of any dyskinesia. Trial discontinuation of the rivastigmine transdermal patch was followed by complete resolution of the symptom.Amiodarone may inadvertently cause neurologic like tremors, parkinsonism, myoclonus, and various dyskinesias, which are linked to idiosyncratic hyperthyroidism.5 In the case of quetiapine, the EPS is expectedly less, as against the other SGA's, and appears late in the course of treatment , and usually occurs after the dosage is decreased or after the drug is discontinued. The dyskinesia often persists for months to years after the discontinuation. Its response to any type of therapy is usually poor.6The complexity in interpreting the choreiform movements in this case lies in that the present case has been receiving occasional low-dose second-generation antipsychotic agent  since 2012. Movement disorders, whether it be acute dystonia, or be tardive dystonia/dyskinesia (choreiform movements included), are “extrapyramidal symptoms (EPS)” that commonly appear among the first-generation antipsychotic agents , after an acute use (days to weeks) or after a chronic use (months to years). Such EPS are also reported in SGA's, but not as prevalent as one would anticipate in the FGA's.7 was being given at lower doses (12.5–25 mg/occasion), and thus EPS would not be an expected cause of the choreiform movements. A single dose of 1 mg risperidone given elsewhere did not also change the clinical occurrence of choreiform movements of this present case.Although applied sparingly in this present case, the much safer quetiapine8 and laterocollis,9 including myoclonus10) for cases with Alzheimer's disease, Parkinson's disease dementia, and Lewy-body dementia. “Pisa syndrome,” or axial deviation, also occurred in dementia cases given galantamine11 and donepezil.12Cases of EPS are reportedly rare in a number of dementia syndromes given anticholinesterases. Donepezil was found to induce cervical dystonias , typical parkinsonism , and EPS  are among the movement disorders linked to organophosphates.Rivastigmine targets the G1 enzymatic form of acetylcholine mostly in the hippocampus and cortex of individuals with Alzheimer's disease. Although of similar chemical structure, unlike organophosphates, which bind irreversibly, and carbamates, which bind reversibly for 8 to 10 hours, rivastigmine binds acetylcholinesterase for only 4 to 6 hours.This case reflects an adverse effect, which has not been seen documented in other studies. The reversal of choreiform movements after discontinuation of rivastigmine (13.3 mg/24-hour dose) poses a causal association that should be further looked into.As the patient is no longer capable to give consent for reporting and publication of this case, her daughter as legal representative and nearest of kin consented in her behalf.


The elemental stoichiometry of microalgae reflects their underlying macromolecular composition and influences competitive interactions among species and their role in the food web and biogeochemistry. Here we provide a new estimate of the macromolecular composition of microalgae using a hierarchical Bayesian analysis of data compiled from the literature. The median macromolecular composition of nutrient-sufficient exponentially growing microalgae is 32.2% protein, 17.3% lipid, 15.0% carbohydrate, 17.3% ash, 5.7% RNA, 1.1% chlorophyll-a and 1.0% DNA as percent dry weight. Our analysis identifies significant phylogenetic differences in macromolecular composition undetected by previous studies due to small sample sizes and the large inherent variability in macromolecular pools. The phylogenetic differences in macromolecular composition lead to variations in carbon-to-nitrogen ratios that are consistent with independent observations. These phylogenetic differences in macromolecular and elemental composition reflect adaptations in cellular architecture and biochemistry; specifically in the cell wall, the light harvesting apparatus, and storage pools. Over 80 years ago Alfred Redfield discovered that plankton have an average atomic C:N:P stoichiometry of 106:16:1 –4. HowevThe C:N:P of microalgae reflects their macromolecular composition ,9. ProtePioneering work by Parsons et al.  on 11 spIt is difficult to reconcile invariance in macromolecular composition across phyla of microalgae with known differences in C:N:P across phyla ,7. PreviIsochrysis , several species of Chaetoceros (n = 129), Thalassiosira (n = 113), Tetraselmis (n = 71), Chlorella (n = 51), Dunaliella (n = 62) and Nannochloropsis (n = 57) have been studied by numerous groups under a range of culture conditions.Macromolecular data for microalgae, predominantly marine phytoplankton, was collected from 130 publications from tables, text and figures. The microalgae macromolecular database and list of data sources is available in http://www.algaebase.org/) was used (2014–2016) to identify synonyms, phyla and if species were freshwater, terrestrial or marine. Species listed as coastal, estuarine or brackish were considered marine. Species from 9 phyla, including the Cyanobacteria, Chlorophyta, Rhodophyta, Bacillariophyta, Cryptophyta, Dinophyta, Euglenozoa, Haptophyta, and Ochrophyta, were collected but the majority of observations are from species within the Bacillariophyta followed by the Haptophyta and Chlorophyta. Very few observations were obtained for the Euglenozoa and Rhodophyta and therefore these data are not used in analyses that compare phyla but are included in the pan-microalgae estimates of macromolecular pools and ratios. Species identified to the genus but not species level were assumed to be different species unless identified as the same strain within or across studies. The majority of observations in the database are from marine species. Under active growth conditions, for protein as percent dry weight, 79% of the observations are marine, for carbohydrate as percent dry weight 80% of the observations are marine, and for lipid as percent dry weight 75% of the observations are marine. All observations for the Cryptophyta and Dinophyta are marine, most of the macromolecular observations for Haptophyta and Ochrophyta are marine, >60% of the macromolecular observations for Chlorophyta are marine, but for the Cyanophyta most of the observations (>60%) are from freshwater species.AlgaeBase an online database of terrestrial, marine and freshwater algae . We then used all estimates of protein to estimate phylogenetic differences in macromolecular composition but excluded protein data estimated from N content for all comparisons to C:N data. A comparison of protein as a percentage of dry weight for exponentially growing microalgae for the different methods is provided in Several methods are used to determine protein content in microalgae. Total nitrogen content (N content) can be measured, often using the Kjeldahl method, and then converted to protein using a conversion factor, or protein can be estimated from peptide residues , or amino acids can be measured and summed. Most of the protein estimates in the database used a Lowry-type assay or N content. Traditionally N content is converted to protein assuming protein is 16% N by mass and all measured N is in protein. The largest non-protein nitrogen pool in microalgae is associated with inorganic nitrogen pools in eukaryotic species . Cyanobayi are the observations, μ is the overall mean, Pj and Sj are the estimated means for each phylum and species, respectively, p[i] and s[i] are the phylum and species, respectively, of observation i, and εi is the residual error for each observation. Each of the estimates  was described by a normal distribution. Three distinct uninformative hierarchical priors were used for the variances of species and phylum means and the error term . The hierarchical model has the effect of partially pooling the data across taxonomic levels, sharing the sampling strength across taxa and leading to smaller variances than would be obtained in a classical regression. This pooling can lead to apparent discrepancies, for example in the protein method analysis (Pp[i] for each macromolecular pool). We computed 50,000 iterations on 4 chains using Rstan and sampled the distribution from the second half of the iterations thinning the samples to every fifth observation [We computed the median macromolecular composition as percent dry weight and the mass ratios of macromolecular pools for nutrient-sufficient exponentially growing cultures using a hierarchical Bayesian model . For comanalysis  the protervation . Consistervation ,7, indepUnder nutrient-sufficient growth conditions the median macromolecular composition of microalgae is 32.2% protein, 17.3% lipid, 15.0% carbohydrate, 17.3% ash, 5.6% RNA, 1.1% chlorophyll-a and 0.98% DNA as percent dry weight Tables . The ashThere are significant differences in the major macromolecular pools, protein, lipid and carbohydrate, across the different phyla of microalgae  and 5. TCompared to the eukaryotic microalgal phyla the Cyanobacteria have high protein (43.1%) and carbohydrate (21.8%) and low lipid (11.7%) and ash (8.1%) as percent dry weight  and the The Bacillariophyta, Ochrophyta, and Haptophyta  are generally higher in lipid (18.6–21.3%) than many of the other phyla examined. The Ochrophyta, dominated in this study by the class Eustigmatophyceae, are particularly high in lipid (21.3%) and the Bacillariophyta are particularly low in carbohydrate (12.2%) as percent dry weight . The BacThe Dinophyta differ from the other eukaryotes in being low in protein and high in carbohydrate as percent dry weight , Table 3Botryococcus braunii, a freshwater species primarily studied for biofuel applications, has the highest lipid as percent dry weight, 43%, while Tetraselmis suecica and Dunaliella tertiolecta, marine species, have several observations across several studies with lipid as percent dry weight ≤10%.There is no significant difference in the overall protein, carbohydrate or lipid as percent dry weight across the marine and freshwater species. At the phylum level, the only significant difference between freshwater , n = 27) and marine species , n = 45) is in lipid as a percent of dry weight in the Chlorophyta. This is likely due to a few marine species with relatively low lipid and a few freshwater species with relatively high lipid as percent dry weight within the database as opposed to a systematic difference in lipid content between marine and freshwater species. The macromolecular composition of actively growing nutrient-sufficient microalgae is distinct from other major domains of life . The micThere are clear differences in macromolecular composition and stoichiometry across phyla of microalgae , Table 3Prochlorococcus [Phylogenetic differences in protein content reflect differences in cell wall composition, the light harvesting apparatus, and storage reserve strategies. For example the phyla with the highest protein as percent dry weight, the Cyanobacteria and Cryptophyta use protein as an integral part of their cell wall. The Cyanobacteria have a peptidoglycan layer of sugars and small peptide chains of amino acids in their cell walls and the Cryptophyta have an outer proteinaceous pellicle . In addirococcus ) and Cryrococcus . Cyanobarococcus . Speciesrococcus . Althoug6H10O5)n) that can develop below the outermost plasma membrane [Ostreococcus, Micromonas, and some Dunaliella, while others such as Tetraselmis have relatively thick cell walls composed of organic scales that coalesce forming a solid cell covering [Chlorella species may contribute up to 22% of the dry weight of the cell [Chlamydomonas can have C:P 14-times lower than the comparative wild-type with a wall [Taxonomic differences in carbohydrate content are consistent with known differences in cell wall composition. The cell wall of Cyanobacteria is rich in carbohydrate: the peptidoglycan layer is tightly bound to polysaccharides and many species have an outer membrane of lipopolysaccharides and some protein, and polysaccharide-rich sheath layers that surround the outer membrane . The higmembrane . The Chlmembrane . Some spcovering ,37. The the cell  and wallh a wall . The Bach a wall  and the h a wall . It has h a wall .Phylogenetic differences in lipid as percent dry weight appear to be due to differences in cell wall composition and investment in storage lipid. The Cyanobacteria have lower lipid content (11.7% of dry weight) than the eukaryotic microalgae. Most bacteria accumulate glycogen or poly3-hydroxybutrate (PHB) or other polyhydroxyalkanoates (PHAs) as energy stores ,43. Somea content, 1.1% dry weight, is consistent with previous work, but both the ratio of chlorophyll-a to other pigments and cellular content will vary with irradiance and can reach much higher values under low irradiance [The Bacillariophyta, due to their siliceous frustules, have the highest and the Cyanobacteria have the lowest ash content as percent dry weight. There is currently not enough information available to determine if there are phylum level differences in RNA and DNA content as a percentage of dry weight . Previouradiance .et al. (2004). Most studies in the database used the phenol sulfuric acid (PSA) method for the determination of carbohydrate, although increased sensitivity can be achieved with the less commonly employed 2,4,6-tripyridyl-s-triazine (TPTZ) and 3-methyl-2-benzo thiazoline hydrazine hydrochloride (MBTH) assays [The compilation of macromolecular data from the literature and hierarchical Bayesian analysis allows us to use data generated from many labs, increasing sample size and taxonomic breadth, to discover phylum-level differences in macromolecular composition despite immense species-specific variability. Along with the advantages of compiling data from the literature are the disadvantages associated with experimental variability. Consistent extraction efficiency across the macromolecular pools, across species, and across labs cannot be assured. Several different methods are used to extract macromolecular pools and there is no way to quantify differences in extraction efficiency across studies in the literature. Methods and standards used to quantify the macromolecular pools also differ across studies. For example there are five common methods used to estimate cellular protein: total particulate nitrogen can be converted to protein using a conversion factor, protein can be determined from peptide residues using the Lowry, Bicinchonicic acid, or Bradford assays, and amino acids can be measured and summed. Each method has its own biases. The Coomassie brilliant blue dye used in the Bradford assay binds disproportionately to arginine and to a lesser degree for a number of other amino acids, and the Lowry method is disproportionally sensitive to tryptophan and tyrosine . The tot) assays ,50. Carb) assays . Most mi) assays  although) assays  often re) assays . Macromo) assays . AlthougHere we find that fundamental differences in cellular architecture and other biochemical and physiological traits across phyla of microalgae are reflected in bulk differences in macromolecular composition. The phylogenetic differences in macromolecular composition, combined with the elemental stoichiometry of the macromolecules, predict the observed phylum-level differences in C:N from laboratory cultures , Table 4S1 FileRaw data collected from literature sources. See (CSV)Click here for additional data file.S1 TableDescription of data in the macromolecular database distributed as “mm-public-database-phylum-level-v1.csv”. The database contains a total of 1562 observations (rows).(DOCX)Click here for additional data file.


Arterial hypertension is a major public health problem and has increasedconsiderably in young individuals in past years. Thus, identifying factorsassociated with this condition is important to guide intervention strategiesin this population.To determine high blood pressure prevalence and its associated factors inadolescents.A random sample of 1,242 students enrolled in public schools of the city ofCuritiba (PR) was selected. Self-administered questionnaires provided familyhistory of hypertension, daily energy expenditure, smoking habit, daily fatintake, and socioeconomic status. Waist circumference was measured followingstandardized procedures, and blood pressure was measured with appropriatecuffs in 2 consecutive days to confirm high blood pressure. Relativefrequency and confidence interval (95%CI) indicated high blood pressureprevalence. Bivariate and multivariate analyses assessed the association ofrisk factors with high blood pressure.The high blood pressure prevalence was 18.2% (95%CI 15.2-21.6). Individualswhose both parents had hypertension and those with high waist circumference  hadhigher chances to develop high blood pressure.Positive family history of hypertension and high waist circumference wereassociated with high blood pressure in adolescents. These factors areimportant to guide future interventions in this population. A designeffect of 1.5 was added to correct the error related to multistage sample selection,as was a 30% margin for possible losses and refusals. Therefore, the total samplewas estimated in 1,276 adolescents.To estimate sample size, the following parameters were considered: (i) population of115,524 adolescents; (ii) confidence level of 95%; (iii) sampling error of 2%; (iv)arterial hypertension prevalence of 7.4%,The probabilistic sample was selected by use of multiple stages. In the first stage,all public middle and high schools in the city of Curitiba were listed andstratified according to the nine administrative regions of the city. In the secondstage, five schools were randomly selected from each administrative region, and, inthe third stage, a simple random selection of one to three classes at each schoolwas performed. The adolescents received an assent term, and their parents, a consentterm, explaining the research objectives and procedures, to be completed andsigned.The family history of arterial hypertension was obtained with a questionnaire sent tothe adolescent's parents or guardians, which indicated if the biological fatherand/or mother had arterial hypertension.23 The increased value for each sex and age group wasdetermined according to the proposal by Freedman et al.24 as ≥ 90th percentile.The waist circumference was measured at a level midway between the last costal archand the iliac crest, following standard procedures.25the mean value obtained being considered. The individuals were classified intosample quartiles according to sex and age group.The daily energy expenditure  was obtained from a 3-day activity recorddeveloped by Bouchard et al.,26 Theindividuals were classified into sample quartiles according to sex and agegroup.The cardiorespiratory fitness was assessed by using the shuttle run test proposed byLéger et al.Youth Risk Behavior SurveyQuestionnaire, translated and validated by Guedes and Lopes.27 That questionnaire inquires howmany days, in the preceding 30 days, cigarettes were smoked. The individuals wereclassified into three categories as follows: cigarettes smoked 10 to 30 days;cigarettes smoked 1 to 9 days; and no cigarette smoked in the preceding 30 days.To define smoking, the adolescents completed the 28 To maintain data quality, thecases with energy expenditure greater than 6,000 kcal or lower than 500 kcal wereexcluded.29 According tothe American Heart Association, in a proper food intake, total fat intake should be< 30%.30The total fat intake was obtained by completing a food frequency questionnairedeveloped for the Brazilian population by Sichieri and Everhart.31 In the present study, the participants were classified intothe following four socioeconomic levels: I, lowest socioeconomic level (classes Dand E); II, classes C1 and C2; III, classes B1 and B2; and IV, highest socioeconomiclevel (classes A1 and A2).The socioeconomic status was classified according to the criteria established by theBrazilian Association of Research Companies.National High BloodPressure Education Program.4 Before that, arm circumference was measured to enable the choiceof the cuff size .4 In addition, theadolescents were asked about having already had their blood pressure assessedbefore.Blood pressure was measured by using the auscultatory method, following theparameters established in the fourth report of the 4Two blood pressure readings were taken at a 5-minute interval, the mean value beingconsidered in this study. If the readings differed more than 2 mm Hg, the protocolwould be repeated.The Fourth Report on the Diagnosis, Evaluation, andTreatment of High Blood Pressure in Children and Adolescents,4 the cutoff values used, according tosex, age and height percentile, were as follows: arterial hypertension - systolicblood pressure (SBP) and/or diastolic blood pressure (DBP) ≥ 95thpercentile; prehypertension - SBP and DBP values < 95th percentile and≥ 90th percentile. Individuals with blood pressure values >120/80 mm Hg were considered prehypertensive.4In accordance with Adolescents classified as prehypertensive or hypertensive were reassessed at asubsequent visit on the day following the first assessment, in which case the secondblood pressure measurement was considered for the analysis. At both the first andsubsequent visit, blood pressure was measured by only one trained professional toprevent interobserver disagreement.t and Mann-Whitney U tests, based on normality of data.Continuous data were described by use of measures of central tendency and dispersionfor both sexes. Continuous data were compared between sexes by use of independentCategorical variables were described by use of relative frequency distribution andits respective 95% confidence interval (95%CI). The chi-square test forheterogeneity was used to compare the differences in the prevalences ofprehypertension, arterial hypertension and high blood pressure  between sexes, and to compare the high blood pressureprevalences in the first and second visits.The association between independent variables and high blood pressure was assessed byuse of bivariate and multivariate analysis (logistic regression). The variables witha p value < 0.25 on bivariate analysis were selected for the multivariate model.The magnitude of the association between the independent variables and high bloodpressure was expressed as odds ratio (OR) and its respective 95%CI. The prevalenceand association analyses were corrected with the complex sample design, using the'complex sample' command of the Statistical Package for the Social Science (SPSS)software, version 17.0. The significance level adopted for all analyses was p <0.05.th October,2012.The methodology of this study was approved by the Research Ethics Committee of theHealth Science Sector of the Paraná Federal University (UFPR), and abided bythe ethical guidelines established by the 196/96 Resolution of the BrazilianNational Health Council (CAAE 04414712.3.0000.0102) on the 25Data of 1,812 adolescents were collected. Of those, 570 adolescents meeting at leastone exclusion criterion were excluded from the final analysis as follows: 28individuals were at least 18 years old; 22 were on anti-hypertensive drugs; 84female adolescents were on oral contraceptives and one was pregnant; 172 adolescentsdid not deliver the family history of arterial hypertension of both parents; 239completed the questionnaires incorrectly; 46 underwent neither anthropometricassessments nor the cardiorespiratory fitness test; and 70 individuals did notundergo blood pressure reassessment.Therefore, this study's final sample comprised 1,242 adolescents aged between 11 and17 years, 646 of whom (52.01%) were females. The age group distribution was asfollows: 11-12 years, 363 individuals ; 13-15 years,697 individuals ; and 16-17 years, 182 individuals. Of the total sample, 34.06% had never undergoneblood pressure assessment.When comparing continuous data between sexes, all variables, except for DBP, weresignificantly higher in male individuals (p < 0.01).2 = 523.1; p < 0.01) between the first and second visit  was observed.2 = 0.01; p =0.91) and arterial hypertension .Considering only the values of the second visit, no significant difference betweensexes was observed in the prevalences of prehypertension .At the second visit, the high blood pressure prevalence was 17.5% (95%CI 14.1-21.4)in the male sex, and 18.8% (95%CI 14.7-23.8) in the female sex, showing nosignificant difference between sexes (X2max), total fat intake, and socioeconomic level].On multivariate model, high blood pressure associated (p < 0.05) with familyhistory of arterial hypertension, waist circumference and total fat intake.32 (8%) and those reported in the Brazilian studies by Vieira etal.33 and Pinto etal.13 .When prehypertension and arterial hypertension were considered together, theprevalences observed in the present study were higher than those reported in aninternational study by Duncan et al.11 haveshown a similar prevalence (18.6%) of high blood pressure, while another studyconducted in the city of São Mateus do Sul, Paraná state, has shown ahigher high blood pressure prevalence than that in the present study .20In Brazil, Romanzini et al.Those studies have assessed blood pressure only at one visit. However, as shown inthe present study, blood pressure reassessment at a subsequent visit is veryimportant, because blood pressure levels can change from one visit to the other,tending to decrease.4 In addition, asapproximately 34% of the adolescents in this study had never undergone bloodpressure assessment, they could be anxious or even frightened, which could yieldincreased blood pressure levels. Thus, individuals with high blood pressure levelsat the first visit might feel more comfortable with the procedures and measurersfrom the second visit on.That reduction in blood pressure levels might be due to a decrease in anxiety andfamiliarization of adolescents with the measuring procedures from the second visiton.8 It is worth noting that inherited factors contribute to thedevelopment of high blood pressure in adolescents, and, in addition, theadolescent's family setting is shared in regard to behavioral factors,9 which can contribute to increase blood pressure levels.Regarding the associations, individuals whose both parents were hypertensive had ahigher chance to develop high blood pressure. This is in accordance with anotherstudy, in which individuals with a history of arterial hypertension had more bloodpressure values exceeding the normal limits.20 Theyhave evidenced that the 'waist circumference' measure can determine the fatdistribution in the abdominal region, being related to metabolic risk, in adults,children and adolescents.34Regarding the association of waist circumference and high blood pressure identifiedin this study, other studies have shown the same tendency.Considering the total fat intake, individuals with an increased fat consumption(≥ 30%) have shown a smaller chance to develop high blood pressure, and,thus, total fat intake is a protective factor against high blood pressure.17 have shown that individuals of both sexes with aninadequate total fat intake had a higher chance to develop high blood pressure.Campos et al.,18 however, havereported no significant association of saturated fat and cholesterol intake witharterial hypertension in the city of Curitiba.Contrary to the present study, Guedes et al.Dietary Approaches to StopHypertension (DASH), recommended by the National Institutes ofHealth (NIH),35considers other important aspects, such as consumption of whole grains, nuts, fishand poultry. In addition, the NIH emphasizes that the diet should be rich inpotassium, magnesium, calcium and fibers, and have a low amount of sodium, red meat,candy, sugar and sugary beverages.35Regarding diet composition, the 30 In addition, theindividuals analyzed can consume other foods that favor blood pressure reduction,such as whole grains, nuts, fish, poultry, and others rich in potassium, magnesium,calcium and fibers.35Regarding those characteristics of a healthy diet, it is worth noting that thepresent study quantified only total fat intake, following the trend of most studiesthat report separately only a few aspects of the diet. Thus, the result of thepresent study should be carefully considered, because a high total fat intake canhave a high proportion of poly- and monounsaturated fats, which are beneficial tohealth.11 while others have reported an inverse or nonexistentassociation.13The other variables assessed in the present study showed no association with highblood pressure, the literature being controversial about that. Regarding sex,studies have reported higher chances of high blood pressure in males,14Regarding age, absolute blood pressure levels increase with age in childhood andadolescence, but this seems not to imply increases in high blood pressure levels inthat age group.16 Nevertheless, a sedentarylifestyle established during childhood is known to strongly relate to a sedentarylifestyle in adulthood, increasing the susceptibility to the negative repercussionsof a sedentary lifestyle in the future, including high blood pressurelevels.36Considering the daily energy expenditure, the literature has shown no association ofphysical activity levels with high blood pressure levels.21 Rodrigues et al.,37 and Fernandes et al.38 have shown no significant association with highblood pressure in both sexes.Regarding cardiorespiratory fitness, Stabelini Neto et al.,16 and of bothsexes,10 because adose-time-response relation is known to exist between tobacco use and thedevelopment of related diseases, that is, the risk increases according to the numberof cigarettes smoked, especially, regarding the duration of the habit.39Regarding tobacco use, some studies have reported no association in young individualsof the male sex15 the lowestsocioeconomic levels,16 and, evenno association.13 According toConstanzi et al.,15 youngindividuals of higher socioeconomic levels would eat more and have a more sedentarylifestyle, increasing their chances of developing high blood pressure. Seabra etal.,40 however, havereported that individuals of the highest socioeconomic strata tend to practice morephysical activities than those less favored.Regarding socioeconomic status, the literature is controversial, showing anassociation of high blood pressure levels with the highest socioeconomiclevels,This study had some limitations, and their analysis can be important for futurestudies aimed at assessing blood pressure and its determinants. The first concernsthe study design, which had a cross-sectional data collection. This type of studycan have reverse causality, that is, exposure and outcome are collectedsimultaneously, making it difficult to determine which preceded the other.Another limitation concerns the self-reported variables , because they rely on the subjects' understanding about the variablesassessed. However, in large-scale studies those variables are extremely usefulbecause they provide the evaluation of several individuals in one single assessmentand because they are interesting alternatives when more precise measures cannot beused.The present study showed a high prevalence of high blood pressure in adolescents ofthe city of Curitiba. In addition, it evidenced that taking a second blood pressuremeasure minimizes the estimates of that outcome among adolescents, probably becauseof their familiarization with the measuring protocol. Nevertheless, the estimateswere greater than those of other Brazilian and international studies.A positive family history of arterial hypertension and increased waist circumferenceassociated with high blood pressure in adolescents. Therefore, special attentionshould be paid to young individuals with increased waist circumference, as well asto those with hypertensive parents. Those population subgroups should be the focusof public policies for blood pressure control in the young population, includingactions related to the lifestyle adopted in the school and family settings.


Cancer-related fatigue greatly influences quality of life in cancer patients; however, no specific treatments have been established for cancer-related fatigue, and at present, no medication has been approved in Japan. Systematic research using patient-reported outcome to examine symptoms, particularly fatigue, has not been conducted in palliative care settings in Japan. The objective was to evaluate fatigue, pain, and quality of life in cancer patients at the point of intervention by palliative care teams.Patients who were referred to palliative care teams at three institutions and met the inclusion criteria were invited to complete the Brief Fatigue Inventory, Brief Pain Inventory, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative.Of 183 patients recruited, the majority (85.8%) were diagnosed with recurrence or metastasis. The largest group (42.6%) comprised lung cancer patients, of whom 67.2% had an Eastern Cooperative Oncology Group Performance Status of 0–1. The mean value for global health status/quality of life was 41.4, and the highest mean European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative symptom item score was for pain (51.0). The mean global fatigue score was 4.1, and 9.8%, 30.6%, 38.7%, and 20.8% of patients’ fatigue severity was classified as none (score 0), mild (1–3), moderate (4–6), and severe (7–10), respectively.Cancer-related fatigue, considered to occur more frequently in cancer patients, was successfully assessed using patient-reported outcomes with the Brief Fatigue Inventory for the first time in Japan. Results suggested that fatigue is potentially as problematic as pain, which is the main reason for palliative care. Cancer-related fatigue (CRF) is defined as “a physical, emotional, and/or perceived fatigue or tiredness, with a persistent and subjective sense related to cancer or cancer treatments that is disproportionate to recent activities and interferes with usual functioning.” The prevThere is evidence that 4 mg dexamethasone is effective for cancer-related fatigue . TherefoIn Japan, Morita et al. researched various symptoms experienced by patients, which were estimated by a palliative care team (PCT) and a palliative care unit, using the Japanese version of the Support Team Assessment Schedule (STAS), in which symptom levels are rated using a scale ranging from 0 to 4 . The preMinton et al. recommend the use of the Fundamental Assessment of Cancer Therapy: Fatigue questionnaire and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) to assess CRF . In addiThis study investigated relationships between fatigue, pain, and QOL by focusing on fatigue in PROs. We selected the BFI, Brief Pain Inventory (BPI), and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative (EORTC QLQ-C15-PAL) as assessment tools and included the Pain Management Index (PMI) to evaluate the correlation between inadequate analgesia and QOL. Our expectation was that fatigue assessed via an appropriate tool would be as prevalent as pain and exert an impact on QOL. The objective of the study was to evaluate patients’ QOL and the prevalence of fatigue and pain at the point of PCT intervention, in order to elucidate relationships between fatigue, pain, and QOL.The protocol for this observational study was prepared according to the Helsinki Declaration and the Ethical Guidelines for Epidemiology Research . EthicalThe following inclusion criteria were applied: 1) aged between 20 and 80 years, 2) a performance status (PS) of 0–3 on the Eastern Cooperative Oncology Group (ECOG) scale, 3) a diagnosis of any type of cancer, and 4) ability to complete the questionnaire unaided. The exclusion criteria were as follows: 1) presence of dementia, agitation, or delirium; 2) presence of a mental disorder; and 3) an investigator’s decision that a request for survey participation would be inappropriate .Of the patients referred to PCTs at three institutions between May 2012 and August 2013, 185  met the inclusion criteria and were invited to complete self-rated questionnaires to determine QOL and fatigue and pain levels.The BFI is a questionnaire, originally developed in English, for which validity and reliability have been verified. It is designed to assess fatigue in cancer patients . OkuyamaThe EORTC QLQ-C15-PAL was developed by reducing the EORTC QLQ-C30, which is a comprehensive evaluation tool for cancer patients receiving palliative care . The EORThe BPI is a comprehensive assessment tool for pain, developed by the Pain Research Group of the World Health Organization Collaborating Centre for Symptom Evaluation in Cancer Care . The valThe PMI is a measure of the appropriateness of pharmacological strategies and compares the potency of prescribed analgesic medications using patient-reported pain levels. Analgesics were classified into four levels: 0: no analgesic; 1: nonopioid; 2: weak opioid; 3: strong opioid. Pain levels were scored as follows: 1–3: mild; 4–7: moderate; and 8–10: severe. PMI scores are calculated by subtracting patient-reported pain levels from analgesic levels, which produces a score range of -3 to 3. Negative scores (<0) indicate inadequate analgesia, and positive scores (≥0) indicate adequate analgesia .The mean scores for each of the 9 BFI items were calculated to produce GFSs, for which mean values were obtained. The proportions of patients in the mild, moderate, and severe fatigue groups were also calculated. Summary statistics were produced for QOL (EORTC PAL-15) and pain (BPI and PMI) upon PCT referral, and the relationship between these scores and fatigue was discussed. Spearman’s correlation coefficients were estimated to determine associations between measured items. JMP-Pro 11 (SAS Institute Inc.) was used in the analysis.Of the 185 registered patients included in the study, data from two, who did not complete the BFI questionnaire, were excluded. The mean (SD) GFS value was 4.1 (2.5), and the mean score (SD) for the worst fatigue experienced (BFI-3) was 4.3 (2.8). Regarding the influence of pain on daily life, the lowest and highest mean scores were found for “relationships with other people” (3.6) and “normal work” (4.8), respectively.Moderate to severe fatigue and pain were reported by 59.5% and 64.1% of patients, respectively.The mean BPI-3 (the worst pain) score was 4.9 (SD 3.0). The supporting information file (S1) summarizes the correlations between all measured items. GFS was strongly positively correlated with all BFI items (0.80–0.89). BFI-6  and nausea and vomiting (0.10) were weakly positively correlated, as were BFI-5 (mood) and dyspnea (0.15)This study evaluated fatigue, pain, and QOL in cancer patients referred to PCTs in three acute care hospitals. Approximately 60% of the patients demonstrated worse than moderate fatigue (according to GFSs), indicating that such patients experience moderate to severe fatigue.Although the proportion of patients experiencing CRF has been reported within a wide range (14–95%), to our knowledge, no Japanese studies have used PROs to assess global fatigue –22. Our GFS results showed that moderate or severe CRF, was found in a high proportion of patients (59.5%). This indicated that the majority of patients referred to PCTs at acute care hospitals experience moderate to severe fatigue.The BFI subscales, BFI-4 to BFI-9, and BFI-8 (relationships with other people) displayed the lowest score (mean: 3.6). This finding may have resulted from only observing inpatients. The hospital environment is presumed to limit relationships with others, which may have been reflected in the scores.In our study, moderate to severe fatigue and pain were reported by approximately 60% and 64% of patients . This inA previous study, reported by PCTs and conducted at one of the hospitals involved in the current study , used a proxy the Support Team Assessment Schedule (STAS) . ModeratLee et al.  reportedIn this study, PMI results  showed tWith respect to symptom scores, average pain and fatigue scores were high at 51.0 and 50.6 respectively, and the emotional functioning score was the highest at 64.5. Pain and fatigue were strongly positively correlated, with a correlation coefficient of 0.4, and emotional functioning and pain and fatigue were strongly negatively correlated, with correlation coefficients of -0.4 and -0.5 respectively. In previous studies, pain, fatigue, and depression have been reported to form symptom clusters –31. In oProportions of patients experiencing moderate and severe fatigue in GFSs and pain on the BPI (classified according to the PMI) were high at 59.5% and 64.1%, respectively. This suggests that fatigue is as problematic as pain for cancer patients hospitalized in acute care hospitals. As approximately 20% of patients experience severe fatigue, it is considered an important symptom that should not be ignored in PCT interventions.Bone metastasis was observed in 35.5% of participants and is commonly assumed to be a cause of pain. All participating study sites were acute care hospitals, and a high proportion of patients, 42.1%, were treated with chemotherapy upon admission to the hospital. Therefore, PCTs in acute care hospitals have the greatest likelihood of observing adverse events. Regarding the timing of PCT intervention, the high proportion of patients with metastasis, at 77.6%, and the median value of 4 months since diagnosis indicated that early stage interventions had not yet been effective.A radical treatment for fatigue is to eliminate the causes. However, in most cancer patients, causes can be specified but cannot be eliminated; therefore, drug treatment is chosen. Medications, such as psychostimulants, phytotherapeutic agents, growth factors, and corticosteroids, show evidence of positive effects , but no Finally, the data should be interpreted cautiously, with consideration of the possible omission of patients with poor PS. Further, patients without pain may not be referred to a PCT. Anemia, considered to exert a strong influence on fatigue, was not assessed in terminally ill cancer patients to avoid unnecessary blood collection. In this study, patients referred to the team were all registered; therefore, the influence of primary doctors’ intentions on the results is undeniable.In conclusion, CRF, considered to occur more frequently in cancer patients, was successfully assessed using PROs with the BFI for the first time in Japan. When patients are referred to PCTs, many complain of fatigue. This suggests that fatigue is potentially as problematic as pain, which is the main reason for palliative care. As treatment choices for CRF are extremely limited in Japan, the research and development of treatments to reduce fatigue is urgently required.S1 Database(XLSX)Click here for additional data file.S1 Dataset(XLSX)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.