It is anticipated that the phase III trial in the United States will begin in 2023. Thus, we have demonstrated that α2 ARs could be suitable targets for treating or managing hypovolemic/hemorrhagic shock. Further understanding of ARs in shock would help find new potential pharmacological targets.Shock is a severe, life-threatening medical condition with a high mortality rate worldwide. All four major categories of shock —hypovolemic, distributive, cardiogenic, and obstructive, involve a dramatic mismatch between oxygen supply and demand, and share standard features of decreased cardiac output, reduced blood pressure, and overall hypoperfusion. Immediate and appropriate intervention is required regardless of shock type, as a delay can result in cellular dysfunction, irreversible multiple organ failure, and death. Studies have shown that dysfunction and downregulation of adrenergic receptors (ARs) are often implicated in these shock conditions; for example, their density is shown to be decreased in hypovolemic and cardiogenic shock, while their reduced signaling in the brain and vasculature decrease blood perfusion and oxygen supply. There are two main categories of ARs, α, and β, each with its subtypes and distributions. Our group has demonstrated that a dose of .02 mg/kg body wt of centhaquine (CQ) specifically activates α2B ARs on venous circulation along with the central α2A ARs after hypovolemic/hemorrhagic shock. Activating these receptors by CQ increases cardiac output (CO) and reduces systemic vascular resistance (SVR), with a net increase in blood pressure and tissue perfusion. The clinical trials of CQ conducted by Pharmazz Inc. in India have demonstrated significantly improved survival in shock patients. CQ improved blood pressure and shock index, indicating better blood circulation, and reduced lactate levels in the blood compared to in-use standard resuscitative agents. After successful clinical trials, CQ is being marketed as a drug (Lyfaquin Shock is the clinical manifestation of extreme dysoxia. Dysoxia is a lack of oxygen supply to, or lack of oxygen used by cells, which limits energy production and leads to cellular dysfunction. Prolonged and/or severe dysoxia can result in an imbalance between oxygen supply and demand at the organ and organ system level, which, if left unchecked or corrected in an untimely or inappropriate manner, causes multiple organ dysfunction and multiple organ failure (MOF) . While avia Gi protein. On the other hand, α1-ARs activation stimulates phospholipase C to generate diacylglycerol and inositol trisphosphate (IP3) mediated by a pertussis toxin-insensitive G protein termed Gp  (The autonomic nervous system (ANS) is known to reflexly regulate MAP through efferent (sympathetic and or parasympathetic) nerves, which affect cardiac output, vasoconstriction, or vasodilation to change the SVR or TPR. The activity of these nerves is mediated through various catecholamines and their adrenergic receptors (ARs). Catecholamines and ARs work through at least four potential mechanisms. First, AR signaling affects blood pressure through actions on the central nervous system; second, by directly controlling the cardiovascular tone; third, by modulating renal sodium flux; fourth, by affecting renin release and modulating the renin-angiotensin-aldosterone system . The catx or Gz) . Moreovex or Gz) . TherefoThe main role of adrenergic receptors is to facilitate the necessary physiologic changes to body systems to promote survival in times of “crisis.” This crisis can be physiological or pathophysiological, as the compensation in times of shock illustrates. As previously discussed, α-adrenergic receptors play an important role in sympathetic response and vasoconstriction, leading to increased effective circulating volume (ECV)  while aln = 5), who were suffering from prolonged and therapy-refractory shock before they started this treatment. Three out of five patients showed an increase in blood pressure and recovered, while two died (n = 75) compared to patients treated with standard antiseptic shock measures (n = 76). Moreover, the esmolol-treated patients had no hazardous effect on circulatory function or perfusion. In times of shock, there is a lack of oxygen, that is, present or dysoxia. As this occurs, the body attempts to compensate by stimulating ARs through α and β stimulation to increase oxygen delivery to tissues, specifically the vital tissues of the brain and heart. Through α ARs stimulation, there is a compensatory increase in blood pressure and effective circulating volume; through β stimulation, there is a compensatory increase in heart rate and contractility. Concomitantly, RAAS activation through decreased renal perfusion mediated by vasoconstriction caused by α receptors, which promotes sodium and water retention, further increasing ECV in an attempt to shunt more oxygen to the brain and heart. As this compensation continues, other organs are starved of nutrients and oxygen, leading to local arteriolar dilation to increase flow to those areas. This flow is postulated to indicate endothelial dysfunction in the brain that initiates the process of decompensated shock . The protwo died . In 2006two died . Schmitt− mouse but not in α2B− or α2C− mouse  to 4 h (p = 0.0494) after resuscitation. After 3 days of resuscitation, significantly higher percentage (69.35%) of CQ patients than control patients (46.88%) had blood lactate level 1.5 mm or less. After 28 days, we observed significantly lower mortality (2.94%) in CQ group than control group (11.76%). CQ patients also showed an increase in PP and SBP. A significant increase in PP in the CQ group suggested improved stroke volume due to CQ resuscitation. A significantly greater number of patients had improved base deficit in CQ than the control group. Also, an 8.8% absolute reduction in 28-day all-cause mortality was observed in the CQ group along with improved acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS) scores (N = 56) and 2.20% in the CQ group (N = 91) (p = 0.03), which indicated statistically significant reduction in mortality in CQ group (®) for hypovolemic/hemorrhagic shock in India (Distribution of α2A and α2B ARs varies based on the vascular bed and size of the vessels and species . Large a) scores . The metCQ group . Based oin India , and a pp = 0.024) of hypoxia-inducible factor 1a (HIF-1α) and reduced (p = 0.03) mitochondrial DNA damage than control rats. We also observed reduced acute kidney injury and apoptosis in kidneys in CQ rats  are required to regulate the shock-induced decompensatory vasodilation and reestablish blood circulation, vascular volume and improve survival in different types of shock.The common characteristics of the decompensatory phase of various types of shock include compromised cardiovascular activities with severe hypotension. Resuscitation with several vasopressors has demonstrated encouraging results, with an increase in vasocontraction and MAP at the initial phase of resuscitation. However, the complex sympathetic and parasympathetic signaling mediated through various ARs complicates the outcomes. Hence, for a better understanding of shock etiology and adrenergic receptor physiology, pharmacological interventions must be investigated for their efficacious use in the treatment and prevention of decompensated shock. Our group has addressed this issue by exploring the effect of α2 specific agonist, CQ, in hypovolemic/hemorrhagic shock. CQ activates α2B and α2A ARs, causing an increase in CO and a decrease in SVR with net results of increased blood pressure as well as tissue perfusion. It also helps in reducing blood lactate levels and improves survival. The clinical trials of CQ conducted in India demonstrated significantly improved survival, improved blood circulation, and reduced lactate level in shock patients compared to in-use standard resuscitative agents. Thus, α2 ARs could be suitable targets for treating or managing hypovolemic/hemorrhagic shock. Nonetheless, a deeper investigation of ARs and pharmacologic modulation of ARs using potent agonists like centhaquine (Lyfaquin


Synechococcus, together with Prochlorococcus, contribute to a significant proportion of the primary production on Earth. The spatial distribution of these two groups of marine picocyanobacteria depends on different factors such as nutrient availability and temperature. Some Synechococcus ecotypes thrive in mesotrophic and moderately oligotrophic waters, where they exploit both oxidized and reduced forms of nitrogen. Here, we present a comprehensive study, which includes transcriptomic and proteomic analyses of the response of Synechococcus sp. strain WH7803 to nanomolar concentrations of nitrate, compared to micromolar ammonium or nitrogen starvation. We found that Synechococcus has a specific response to a nanomolar nitrate concentration that differs from the response shown under nitrogen starvation or the presence of standard concentrations of either ammonium or nitrate. This fact suggests that the particular response to the uptake of nanomolar concentrations of nitrate could be an evolutionary advantage for marine Synechococcus against Prochlorococcus in the natural environment.Marine IMPORTANCE Marine Synechococcus are a very abundant group of photosynthetic organisms on our planet. Previous studies have shown blooms of these organisms when nanomolar concentrations of nitrate become available. We have assessed the effect of nanomolar nitrate concentrations by studying the transcriptome and proteome of Synechococcus sp. WH7803, together with some physiological parameters. We found evidence that Synechococcus sp. strain WH7803 does sense and react to nanomolar concentrations of nitrate, suggesting the occurrence of specific adaptive mechanisms to allow their utilization. Thus, very low concentrations of nitrate in the ocean seem to be a significant nitrogen source for marine picocyanobacteria. Due –the cell . Thus, 2ein PipX . NtcA isein PipX , 25. Thece TAN3T .Most cyanobacteria have the capability to take up and assimilate nitrate , 22, 27.nrtA, nrtB, nrtC, and nrtD genes  , the affinity for nitrite is much lower than that for nitrate in the case of the NrtP transporter  encoded by the tD genes , 30 for ed napA) , 32 for nsporter . Relatednsporter .Synechococcus strains has been related to its ability to grow over a wide range of light intensities and spectral qualities , nanomolar changes in nitrate concentrations occurred. This change was stoichiometrically consistent with the subsequent cellular production of a bloom of these cyanobacteria . In thiSynechococcus WH7803 encompasses genes encoding all needed molecular elements to take up nitrate and/or nitrite into the cell and to reduce these inorganic nitrogen compounds to ammonium. Synechococcus WH7803 genomic region bearing its nitrate assimilation gene cluster distributed along 13,300 bp. Accordingly with the most common arrangement of the nitrate assimilation genes in marine cyanobacteria, nrtP and narB genes , are closely located and transcribed in the same orientation, with only 82 bp between the end of the nrtP coding sequence and the start codon of narB. Although nirA, encoding nitrite reductase, frequently takes part of the same operon together with genes encoding the nitrate/nitrite transporter and nitrate reductase in freshwater cyanobacteria  with the structure GTAGCGATTGCAAC-N22-TGCAAT (with TAC changed to AAC and TAN3T changed to TGN3T) and GTAACAACGGCTAC-N22-TGTGAT (with TAN3T changed to TGN3T), respectively, while a less canonical putative site was found 304 bp upstream of the narB tss, centered 221 bp upstream of the stop codon of nrtP: GTGACCTACCTCAC-N21-TTGGAT . For nirA, a putative NtcA-binding site was identified 142 bp upstream of this gene tss with the sequence GTTCGAACTGCTAC-N22-AAAACT (with GTA changed to GTT and TAN3T changed to AAN3T), while another putative site was found 200 bp upstream of the nitM tss: GTCACGGCCGTCAC-N24-CACCAT .The repression of nitrate assimilation genes by the presence of ammonium in cyanobacteria is mediated by NtcA, and it is not affected by the presence or absence of nitrate . Thus, aSynechococcus WH7803 genomic region bearing this nitrate assimilation gene cluster, two additional genes associated with an NtcA-binding site can be identified: cynS, encoding cyanase, the enzyme catalyzing the bicarbonate-dependent decomposition of cyanate into ammonium and CO2, and cnaT, encoding a positive regulatory element of the nirA operon expression as described for Nostoc sp. strain PCC 7120 , while an NtcA-binding site linked to a −10 box was found for the cnaT gene: GTTCAGCCAGCAAC-N22-TCTGGT , centered 213 bp upstream of this gene tss. Additionally, a canonical NtcA-binding site, GTATCAACGACTAC, is placed 57 bp upstream of the cnaT tss, although no recognizable –10 box is associated with it.In the PCC 7120 . A putatSynechococcus WH7803 , were used to define the likely structure of the consensus NtcA-binding site for this strain . The effect of different nitrogen concentrations on Synechococcus WH7803 YII is shown in t test) differences among the tested sources after 24 h; therefore, the data obtained suggest that photosynthesis is not strongly affected.Another important parameter to monitor the status of cells in a cyanobacterial culture is its effective photochemical quantum yield of photosystem II (YSynechococcus WH7803 cells were grown under different nitrogen sources (P = 0.0011), suggesting that the nanomolar nitrate condition may be an intermediate situation, in which the machinery to assimilate nitrate is still upregulated.In cyanobacteria, the signal controlling the C/N balance is the level of intracellular 2-OG , 28, 50. sources . With amSynechococcus WH7803 (P = 0.0494) compared to that detected for cells growing with ammonium as the nitrogen source. Nevertheless, cultures under nitrate (at nanomolar and micromolar concentrations) did not change significantly compared with the control condition under ammonium  and nitrate reductase  are two key enzymes in nitrogen metabolism. Nitrate reductase catalyzes the first reaction in the two-step reduction of nitrate to ammonium, while glutamine synthetase is responsible for the incorporation of ammonium into organic N compounds. Both activities were determined under different nitrogen sources in s WH7803  and F. Tammonium . RegardiTranscriptomic analyses were carried out to get a comprehensive overview of the response to the lack of nitrogen versus the addition of a nanomolar concentration of nitrate.Synechococcus WH7803 encodes 2,530 proteins (UP000001566 in the UniProt database). This transcriptomic analysis identified 2,505 genes representing 99% of the genome . Using a cutoff of a >1.5-fold change and a P adjustment value of <0.05, 862 and 819 genes showed differential expression under nitrogen starvation or with a nanomolar concentration of nitrate, respectively, compared to ammonium . Gene IDs for all these ORFs were used to retrieve the corresponding UniProt entries (https://www.uniprot.org/uploadlists), allowing the identification of 67 of the upregulated (39.88%) and 52 of the downregulated (38.81%) genes (Table S4).Significant changes were observed for 168 upregulated and 134 downregulated open reading frames (ORFs) encoding gene products labeled “hypothetical proteins” by the NCBI database for the ntcA (13.84 versus 13.28), glnB (2.06 versus 2.09), encoding the signal transduction protein PII, glnA (2.10 versus 2.01), encoding glutamine synthetase, amt1 (45.95 versus 47.39), encoding the ammonium transporter, cynS (273.76 versus 289.39), encoding cyanase, nrtP (20.40 versus 19.12), narB (7.53 versus 7.56), nirA (159.15 versus 161.64), and nitM (55.87 versus 58.75). It is worth noting that the highest values of expression under both experimental conditions included those obtained for genes encoding the key proteins involved in nitrate assimilation: nitrate transporter NrtP, nitrate reductase, nitrite transporter NitM and nitrite reductase, although the expression of these genes did not seem to be affected by the addition of nanomolar concentrations of nitrate with respect to nitrogen starvation. The cynS gene, with a putative NtcA-regulated promoter, showed very high values of expression, even higher in cultures growing under nanomolar nitrate concentrations. However, other genes, such as icd, encoding isocitrate dehydrogenase , or pipX, encoding the signaling protein PipX, which are generally upregulated by nitrogen starvation in cyanobacteria, did not show a significant variation of their expressions under these conditions.Genes encoding the main enzymes and regulatory proteins involved in nitrogen metabolism which showed an increase in their expression with respect to the ammonium control did not, however, exhibit a differential response under both nitrogen starvation and nanomolar nitrate concentration conditions . That was the case for SynWH7803_1243; SynWH7803_1470; SynWH7803_0137; SynWH7803_1244; SynWH7803_1045; SynWH7803_1471, and SynWH7803_1469). Two transporters were downregulated only in the nanomolar nitrate cultures (SynWH7803_1470 and SynWH7803_0137), and other one only under nitrogen starvation (SynWH7803_1469). Furthermore, under our study conditions, another set of transporters and permeases was upregulated. The ammonium transporter showed slightly lower expression on the cultures grown in the absence of nitrogen sources with respect to those at a nanomolar nitrate concentration (45.9 versus 47.4). Moreover, the nitrite transporter showed a similar pattern (55.8 versus 58.7). As we expected, the MFS nitrate transporter was upregulated, although the level of expression was almost the same at both conditions (20.4 versus 19.1).An essential part of the ecological success of the marine picocyanobacteria is the nutrient acquisition mechanisms, such as the use of high-affinity ATP-binding cassette (ABC) transporters to competitively acquire nutrients, especially in oligotrophic marine environments . Our traII of Synechococcus WH7803 cultures growing in nitrogen starvation or at a nitrate nanomolar concentration seemed not to be affected compared to the control culture, the expression of most genes encoding subunits from photosystems I and II displayed a general downregulation as follows: from photosystem I, psaB (−2.46 versus −2.20), psaI (−2.00 versus −1.72), psaK (−2.77 versus −2.34), and psaL (−3.08 versus −2.65) and from photosystem II, psbA (−2.01 versus −1.72), psbL (−1.90 versus −1.57), and psbM (−2.50 versus −2.19). Additionally, there are two copies of the genes encoding the photosynthetic pigment PE, cpeBA and mpeBA , cpeA (−5.69 versus −4.58), mpeE (−4.09 versus −3.52), cpeE (−3.55 versus −3.05), and cpcG2 (−3.79 versus −3.08). The absence of nitrogen for PE synthesis seems to lead to the downregulation of the genes involved in this pigment synthesis, although the availability of just a low concentration of nitrate could be perceived by Synechococcus WH7803 cells, and consequently, the negative effect on the transcription of those genes would get reduced.Although the Ynd mpeBA , in the  operons , and oth operons . While tSynechococcus WH7803. With no significant differences between nitrogen starvation and nanomolar nitrate concentration conditions, the expression of genes encoding the ATP synthase subunits decreased with respect to the control condition (800 μM ammonium): atpE (−3.49 versus −3.04), atpC (−5.47 versus −5.05), atpA (−6.27 versus −6.07), atpD (−7.19 versus −6.60), atpF (−5.70 versus −5.85), atpG (−6.52 versus −7.22), atpH (−8.72 versus −8.14), and atpI (−5.03 versus −4.98). Furthermore, genes encoding subunits of the ribulose 1,5-bisphosphate carboxylase (RuBisCO) together with those encoding carboxysome shell proteins were also downregulated under both conditions: rbcL (−3.95 versus −3.34), rbcS (−5.80 versus −4.45), csoS2 (–6.13 versus −4.99), csoS3 (−7.18 versus 6.18), ccmL (−2.56 versus −2.80), and csoS4 (−3.77 versus −4.19). It is worth noting that most of these genes related to carbon fixation showed a differential response to the absence of nitrate versus the addition of a nanomolar concentration of nitrate, as was also the case for photosynthesis-related genes.As might be expected for a photosynthetic organism, a general downregulation observed for genes encoding the subunits of the photosynthetic apparatus and those proteins involved in the synthesis of the phycobilisome was also observed for genes related to the energetic metabolism of Prochlorococcus and Synechococcus (SynWH7803_0567), 2.13 versus 2.11 (SynWH7803_0607), and 2.57 versus 2.68 (SynWH7803_0745). YkuD is an l,d-transpeptidase catalytic domain involved in the peptidoglycan cross-linking in the cell wall, thus participating in the bacterial secretion process (SynWH7803_0924) has also been identified showing a strong upregulation under both conditions: 6.75 versus 6.84. The lipocalin protein family includes a large group of eight-stranded β-barrel extracellular proteins which are characterized by their ability to enclose an internal ligand-binding site for a range of small hydrophobic molecules and to form complexes with soluble macromolecules  for 326 proteins, which corresponds to 13% of the predicted proteome. The most abundant proteins in the proteome of Synechococcus WH7803 were several isoforms of C-PE , followed by several oxidative stress response proteins such as superoxide dismutase (UniProtKB A5GMK3), ferredoxin (UniProtKB A5GN90), thioredoxin (UniProtKB A5GM53), and peroxiredoxin (UniProtKB A5GKS9). The nitrogen regulatory protein PII (UniProtKB A5GNE6) is also one of the most abundant proteins in the cell, independently of the source of nitrogen used (Table S5).Absolute quantification was obtained using the HiSynechococcus cells sense nanomolar concentrations of nitrate and develop a specific response different from that under nitrogen starvation.Changes identified in the proteome were not dramatic: a total of 28 proteins changed significantly comparing nitrogen starvation versus control conditions, and 41 changed significantly comparing a nanomolar concentration of nitrate versus control conditions. Principal-component analysis (PCA) of significantly changed proteins in a nanomolar concentration versus the control  shows a A5GPQ6). This enzyme shows a 16-fold increase in 800 nM nitrate (P = 0.01) and a 14.8-fold increase under nitrogen starvation (P = 0.02).As shown by the RNA-seq data, one of the proteins with the highest increase is ferredoxin-nitrite reductase; however, protein quantification was very variable between replicates, and statistical test results were not significant . In goodP = 0.04 and P = 0.03, respectively).Results of the quantification of PE  are compProchlorococcus sp. strain SS120 . The thioredoxin with the code UniProtKB A5GN01 showed a significant increase under nitrogen starvation and in nanomolar concentrations of nitrate   and nitrite reductase (nirA) increased compared with N starvation. In cyanobacteria, the transcriptional factor NtcA regulates both genes encoding the enzymes involved in nitrate assimilation, nitrate reductase, and nitrite reductase, as well as ntcA, which also presents a promoter with an NtcA-binding site. At 24 h, the expression of ntcA seemed to be similar under all tested conditions. However, narB and nirA still showed higher expression values under 800 nM nitrate than in nitrogen starvation, and interestingly, the expression was even more increased with 800 μM nitrate.To broaden the analysis of the response at 24 h by transcriptomic and proteomic approaches, the effect of nitrogen source at different times  was also studied in qRT-PCR) . The resSynWH7803_1012  is a downregulated ORF (−7.46 versus −4.29), and SynWH7803_RSS12335  is upregulated (+193.92 versus +238.82).Two ORFs showing a clear differential response to the absence of nitrate versus the addition of a nanomolar concentration of nitrate were selected among the nonannotated ORFs for gene expression analysis by qRT-PCR on the basis of the transcriptomic results. SynWH7803_1012 encodes a 112-amino acid (aa) membrane protein with an extracellular N-terminal domain (residues 1 to 27), a transmembrane domain (residues 28 to 43), and an intracellular C-terminal domain (residues 44 to 112), as predicted by the PSIPRED . PSIPRED  and MEMS PSIPRED  softwareSynWH7803_RSS12335 is an ORF of 135 bp which would encode a 44 aa-peptide. While PSIPRED predicted two alpha-helix segments for this peptide , UniProt indicated 52.6% identity (65.85% of positives) with nitrite reductase from Synechococcus sp. CB0101 and 44.4% identity (55.6% of positives) with nitrite reductase from Prochlorococcus sp. NATL2A, although this peptide is clearly smaller than those enzymes. The possibility of cotranscription of nirA, SynWH7803_RSS12335, and nitM was tested by reverse transcription-PCR (RT-PCR) performed with RNA isolated from Synechococcus WH7803 cells grown with ammonium and then transferred to a medium supplied with 800 nM nitrate for 24 h. After reverse-transcription with a primer annealing just a few nucleotides from the end of nitM, amplification products were obtained corresponding to parts of these three genes: nirA, SynWH7803_RSS12335, and nitM . The results indicated that cotranscription of these genes takes place.SynWH7803_1012 and SynWH7803_RSS12335 was also studied in Synechococcus WH7803 cultures with different nitrogen sources at different times  by qRT-PCR. For SynWH7803_1012 we observed nonsignificant changes at early times (3 and 6 h) for nitrogen starvation and micromolar and nanomolar concentrations of nitrate with respect to ammonium-supplied cultures, while at 24 h, a striking downregulation of this ORF was observed under those conditions: −61.09 (N starvation), −50.18 (800 nM nitrate) and −72.19 (800 μm nitrate). Although qRT-PCR confirmed the lower downregulation of this ORF under the nanomolar nitrate conditions than under nitrogen starvation, an even higher decrease of its expression was observed after 24 h in a micromolar nitrate concentration. The function of this predicted membrane protein that was strongly downregulated after 24 h without ammonium still needs to be elucidated. The SynWH7803_RSS12335 ORF showed a strong upregulation at each time included in this study for the three conditions, reaching the highest value at 6 h. Cultures growing with nitrate as the sole nitrogen source, at either micromolar or nanomolar concentrations, always showed a stronger upregulation than that for nitrogen starvation, and it is worth noting that the expression of this ORF was higher with the nanomolar nitrate concentration than with the micromolar concentration at 6 and 24 h. Despite being transcribed in the same mRNA and sharing a general upregulation at each time and experimental condition studied, nirA and SynWH7803_RSS12335 showed a differential gene expression time course, pointing to a specific RNA processing.Expression of Synechococcus has been investigated to a far lesser extent than in freshwater cyanobacteria, and while there are similarities in some strains, there are also some intriguing differences  compared with WH8018 , which lost 85% of the pigments  is intriguing and deserves further research. It is particularly surprising that SynWH7803_1012 and SynWH7803_RSS12335 show significant homology with some parts of NtcA and nitrite reductase, respectively. This might suggest that these ORFs could have evolved from previously existing genes involved in standard nitrogen assimilatory pathways, which were adapted to respond to very low nitrate concentrations in marine environments.The specific response of genes not related to known functions, II as one of the most abundant proteins in Synechococcus WH7803. To our knowledge, the main reported function of PII thus far is the control of the C/N balance in cyanobacteria , and cofactors (NAD+)  . AlthougPCC 7942 , regulatSynechococcus, leading to specific changes in its transcriptome and proteome, which are different from those provoked by nitrogen starvation. Further studies are required to analyze whether this organism has developed uptake mechanisms allowing it to scavenge nanomolar concentrations of nitrate (as suggested by preliminary studies from our team) and the molecular underpinnings enabling its detection.Primary production in the oceans is supported by two major forms of nitrogen: ammonium, which is a reduced form provided by the recent decomposition of organic matter in the water column, and nitrate, which is an oxidized form and diffuses into the euphotic zone from deep water. It is generally believed that ammonium is a major source of nitrogen for phytoplankton in oligotrophic oceans. However, some studies suggested that nitrate might also play an important role , 77. ThiSynechococcus WH7803 was grown in a chemically defined artificial seawater medium (ASW) (−2 s−1). Growth was determined by measuring the absorbance of cultures at 750 nm, and cells were collected during the exponential phase of growth, when absorbance at the indicated wavelength was 0.1.um (ASW) . Cells wg for 8 min at 24°C using an Avanti J-25 Beckman centrifuge equipped with a JA-14 rotor. Cell pellets were washed twice with ASW medium with no nitrogen source added and then resuspended in ASW medium supplemented with either no nitrogen or different forms of nitrogen sources, namely, ammonium [(400 μM NH4]2SO4), and nitrate (800 nM or 800 μM KNO3). Cultures were then kept under standard light and temperature conditions for 24 h. Cells were harvested by centrifugation at 26,000 × g for 8 min at 4°C. Cell pellets were resuspended in 2 mL of 25 mM ammonium bicarbonate for proteomic studies, in 10 mM sodium acetate (pH 4.5), 200 mM sucrose, and 5 mM EDTA for RNA analysis, and in 50 mM Tris-HCl, (pH 7.5), for protein assays. Samples for proteomic studies and protein assays were stored at −20°C until use and those for RNA analysis, at −80°C.To prepare the experiments, cultures with 800 μM ammonium (8 L) at 0.1 units of absorbance at 550 nm were centrifuged at 26,000 × Protein concentration in soluble fractions was determined using the Bio-Rad protein assay according to the Bradford method .g, for 8 min at 4°C. The cell pellets were resuspended in 2 mL of ASW medium and used to fill a 24-well culture plate (Biofil). The samples were incubated in the dark for 30 min. Then, the fluorescence of the chlorophyll was measured using a PAM WALZ IMAG-K5 imaging system. The photosynthetic radiation used was 36 μmol quanta m−2 s−1.A total of 250 mL of culture was centrifuged at 26,000 × 6 M−1 cm−1.Phycoerythrin (PE) was measured as described by Wyman . PE concg and 4°C. The supernatants were used for the determination of 2-OG using an enzymatic method based on the oxidation of NADPH in the reaction catalyzed by the glutamate dehydrogenase as previously described  as previously described (http://primer3plus.com) on the base of the published genome of the Synechococcus WH7803 strain. The specificity of the qRT-PCRs was checked for single amplification of DNA fragments of the expected size by agarose gel electrophoresis and for identification by Sanger sequencing ; Universidad de Córdoba). qRT-PCRs were performed as previously described  were purified with the RNA Clean & Concentrator-5 kit (Zymo Research). The purity and concentration of each total RNA sample were measured using a NanoDrop ND-1000 spectrophotometer (Thermo Fisher Scientific), while their quality and integrity were assessed using a Bioanalyzer 2100 instrument (Agilent Technologies) to obtain the corresponding electropherograms. Libraries for Illumina sequencing were prepared using ribosome-depleted RNA samples. RNA-sequencing performed on the Illumina HiSeq 2000 platform and alignment procedures were conducted by Sistemas Genómicos .Synechococcus WH7803 genome (ID NC_009481.1), and the quality of these reads was controlled using Picard Tools (http://broadinstitute.github.io/picard/). The assembly and identification of the transcripts were performed using Cufflinks v2.11 software, while the transcript quantification was carried out with the HTSeq algorithm (http://www-huber.embl.de/HTSeq/doc/overview.html). To assess the normalization of the differential expression analysis, the DESeq2 algorithm was used applying a negative binomial distribution model , 800 nM nitrate, and nitrogen starvation. After 24 h, RNA was isolated as described in Materials and Methods; the quality parameters of the isolated RNA are shown in Table S6. The total qualified mRNA-based sequence reads identified after a step data filtering process are in Table S7. Regarding the quality of the sample, the percentage of the properly pair indicates the high quality of the mapping. Moreover, the data reflect homogeneity among triplicates. In order to get a better comparison among samples, these have been normalized with respect to the length of the genes and the size of the library, as shown in Fig. S5A and B The study of the quality of the differential expression among the samples  showed that the obtained results fit the model. Furthermore, the MA plot (M is the log ratio and A is the mean average)  shows the number of genes that are differentially expressed between conditions.Three biological replicate experiments of 18 precolumn  for 3 min at 5 μL/min in 98% acetonitrile (ACN)/0.1% trifluoroacetic acid (TFA) as the loading buffer. Then, a chromatographic gradient of 4 to 40% ACN was performed on a C18 nano-column  at a flow rate of 300 nL/min for 60 min. The total chromatography time was 85 min. Eluting peptides were analyzed on an Orbitrap Fusion device (Thermo Fisher Scientific) operated in top 50 data-dependent acquisition mode, selecting for fragmentation the top 50 ions of the highest intensity from each full scan at a maximum duty cycle time of 3 s. The mass range acquisition in full-scan mode was 400 to 1,500 m/z in the Orbitrap at a resolution of 120 K, a 4 × 105 automatic gain control (AGC) ion count target, and a maximum injection time of 50 ms. Tandem mass spectrometry (MS2) was performed by quadrupole isolation at 1.2 Th. Only precursors with a charge state of 2 to 5 were sampled for MS2, setting a dynamic exclusion window of 15 s and allowing a 10-ppm tolerance for the selected precursor. Fragmentation was performed by collision-induced dissociation (CID) at a normalized collision energy of 35. Fragment ions were analyzed in the ion trap. Liquid chromatography-tandem mass spectrometry analysis was carried out at the proteomic facilities of SCAI.Three biological replicates were processed for the proteomic analysis as previously described, using trypsin as the protease , 91. The3 strategy in Progenesis QI (Waters Corporation). “Normalize to all proteins” was selected in Progenesis QI as the normalization method to correct from protein loading. The peak list generated in Progenesis QI was searched against a database containing all entries for Synechococcus WH7803 in UniProt (www.uniprot.org) . As the internal standard for absolute quantification, rabbit phosphorylase B  was added to each sample (50 fmol on column). Search parameters were set as follows: trypsin was selected as the protease for digestion, allowing one missed cleavage and setting carbamidomethylation of cysteines as fixed modification and methionine oxidation as variable modification. Precursor mass tolerance was set at 10 ppm, product ion tolerance at 0.5 Da, and false-discovery rate (FDR) at 1%. Since nonaxenic cultures were used in the experiments, protein concentration was further corrected using total protein abundance to account for differences in the populations of Synechococcus in cultures. For a protein to be considered significantly differentially expressed, we used the following criteria: identified and quantified using at least two unique peptides and with a P value of ≤0.05.Absolute quantification of proteins was calculated using the Hihttps://www.ncbi.nlm.nih.gov/bioproject/PRJNA830281.The proteome data set is available at the PRIDE repository with the following information: project name: “Marine Synechococcus sp. strain WH7803 shows specific adaptative responses to assimilate nanomolar concentrations of nitrate”; project accession no.: PXD031142; project DOI:10.6019/PXD031142. Transcriptome data have been deposited in the NCBI public repository at


To compare the intra-device repeatability and inter-device reproducibility between two anterior segment imaging instruments, the CASIA SS-1000  and Pentacam  in measuring anterior segment parameters.Single-center, prospective clinical trial. Participants ≥20 years of age were included. One eye was randomly selected, each imaged by three CASIA SS-1000 devices and three Pentacam devices by three different examiners. Each photographer operated a pair of devices, one CASIA SS-1000 and one Pentacam. The image order for each participant was determined by a random permutation table. Three images were taken from each device. A total of 18 images were taken for each eye. Ratios of the standard deviations, referenced as (CASIA/Pentacam), were calculated to compare the repeatability and reproducibility of the two imaging instruments.In all, 66 participants with a mean age of 46.4 years (±21.7) were enrolled in the study. All repeatability ratios and intra-device variability were less than 1 . All reproducibility ratios, which measure the inter-device variability, were less than 1 . A ratio of less than 1 indicates that the CASIA SS-1000 has more consistent measurements.The CASIA SS-1000 was found to have better repeatability and reproducibility compared to the Pentacam for both corneal curvature and pachymetry maps. This greater consistency may require further study to determine whether the decreased variability can be translated into improved clinical results. Accurate measurements of the cornea are becoming increasingly important. Clinicians are using precise quantitative measurements of epithelium, stroma and endothelium to evaluate patients and improve surgical outcomes. Surgical planning before femtosecond laser-assisted treatments now requires precise stromal thickness to avoid sacrificing the stromal bed < 250 μm). Pachymetry maps are relied on for any pre- and post-laser surgery evaluation, especially in subclinical and early diagnosis of corneal ectasia or form fruste keratoconus , 2. Furt50 μm. PaDue to operator-dependent accuracy of contact tomography with ultrasound, accurate noncontact topography and tomography have evolved quickly. Scheimpflug systems, such as the Pentacam, allow for analysis of distorted and aberrated corneas, with true elevation measurements of both the anterior and posterior surfaces of the cornea. However, this technique is limited by cornea clarity, pupil diameter, and iris reflections . Within Since very small differences in corneal measurements alter clinical decisions, reproducibility and repeatability are extremely important in obtaining measurements from noncontact tomography. Studies have examined the inter-operator reproducibility and repeatability of a single Scheimpflug machine with a single OCT machine in corneal thickness and anterior chamber measurements in both healthy and postoperative eyes –11. Howeclinicaltrials.gov (NCT02077790) on 04/03/2014. All research adhered to the tenets of the Declaration of Helsinki and was HIPAA compliant.This prospective, single-center study was approved by the Institutional Review Board/Ethics at Ehime University Hospital, Shitsukawa, Toon, Ehime, Japan, and was registered on In all, 66 consecutive adult subjects (at least 20 years of age) were recruited. After obtaining informed consent, demographics, medical/ocular history, and present ocular medications were recorded. Eyes were excluded if they had any previous intraocular or corneal surgery (except laser refractive surgery), used a rigid contact lens within 1 week or soft contact lens within 24 hours, were currently on mydriatic and/or miotic medications, or were incapable of fixating at the internal fixation light or opening the eye sufficient to image a full image area. When both eyes of the participant were eligible, one eye was randomly selected by coin flip.Study eyes underwent a series of imaging by three CASIA SS-1000 devices and three Pentacam devices. These devices were placed in three separate rooms. In each room, one CASIA SS-1000 and one Pentacam were installed and one examiner was assigned to operate the devices. Three images were taken by each of six devices. A computer-generated, randomization schedule was used to determine the order of the rooms/examiners and the order of the devices (CASIA SS-1000 vs. Pentacam) in a room. The exam procedure took approximately 1 h for imaging a total of 18 images in each eye. With this design, the device effect and examiner effect were confounded, and is called the [device+examiner] effect throughout the rest of this paper.The CASIA SS-1000 is a three-dimensional, noncontact, noninvasive, imaging system based on the principle of “swept-source” OCT. This system achieves high-resolution imaging of 10 μm  and 30 μm (transverse) and high-speed scanning of 30,000 A-scans per second. All images were taken in 3D mode using the “corneal map” scan.. In addition, to reduce examiner-dependent variability, the CASIA SS-1000 auto-alignment/auto shot and Pentacam’s automatic release mode were used. This way each instrument automatically determines when correct focus and alignment is achieved and then performs a scan.The Pentacam is a rotating Scheimpflug camera. It is a noncontact, noninvasive system that uses a monochromatic slit-light source (blue LED at 475 nm) for measuring anterior segment tomography. Twenty-five images with 500 measurement points on the front and the back of the corneal surface are acquired over a 180-degree rotation in 2 s. All images were taken by 3D scanning of 25 Picture/1 SecAnterior axial power of the flattest meridian Anterior axial power of the steepest meridian Posterior axial power of the flattest meridian Posterior axial power of the steepest meridian Central corneal thickness Thinnest corneal thickness Horizontal location of thinnest corneal point , in which 0 indicates the apex, positive value for the temporal direction, and negative value for the nasal direction (TCP(X), mm)Vertical location of thinnest corneal point from apex (TCP(Y), mm), in which 0 indicates the apex, positive value for the superior direction, and negative value for the inferior directionPeripheral corneal thickness at intersection between the 2-mm diameter circle and the nasal horizontal meridian Peripheral corneal thickness at intersection between the 4-mm diameter circle and the nasal horizontal meridian Peripheral corneal thickness at intersection between the 6-mm diameter circle and the nasal horizontal meridian All measurements are performed in constant, dim-lighting conditions. Several corneal curvature and corneal thickness measurements were obtained from each image by each instrument:Repeatability (intra-device) SD—the variation of measurements taken by each device for each eye; andReproducibility (inter-device + intra-device) SD—the variation of measurements taken by all three devices, by each instrument, for each eye.Demographics were summarized by mean and standard deviation (SD) for continuous variables or by frequency (%) for discrete variables. The repeatability and reproducibility were evaluated by:Repeatability SD and Reproducibility SD were calculated for each device using a random effect model with random effects, participants (66 participants) and devices + examiners (three devices + examiners). The ratio of CASIA SS-1000 SD to Pentacam SD for each measure was computed for repeatability, reproducibility, and agreement. A ratio of less than 1 indicates that CASIA SS-1000 is more consistent than Pentacam, and vice versa. The coefficients of variation (CVs) were also calculated by repeatability SD/mean and reproducibility SD/mean.Agreement, mean difference (bias) and limits of agreement (LOA) between CASIA SS-1000 and Pentacam was calculated. In addition, Deming regression analysis, which allows measurement errors in both CASIA SS-1000 and Pentacam, was used to examine any systematic deviations and estimate the conversion equations. Bland-Altman agreement plots and Deming regression plots were graphed.Statistical analysis was performed using PROC MIXED procedure in SAS for Window 9.4 . Bland-Altman agreement plot was generated using BA.plot and Deming regression analysis was performed using Deming in MethComp package using R × 64 Version 3.01.In all, 66 eyes of 66 participants were included in the study. The mean (±SD) age was 46 (±22) years (range 23–79 years). Of 66 study eyes, 32 (48%) were right eyes and 35 (53%) were from male subjects. Most eyes had no corneal pathology . Other ocular pathologies can be seen in Table Complete results are shown in Table All reproducibility SD ratios were less than 1, indicating the CASIA SS-1000 is more consistent Table . The ratP = 0.71) and 0.02 D (P = 0.39) for flat and steep meridian, respectively, and 95% of the differences for the flat meridian were within 0.70 D and 0.87 D for the steep meridian. The CASIA SS-1000 posterior corneal curvature was flatter by 1.13 D (P < 0.001) and 1.35 D (P < 0.001) in flat and steep meridian, respectively, compared to the Pentacam. The widths of LOAs for posterior corneal curvatures were about 2.5 times wider than the LOA widths for anterior curvatures.Bland-Altman agreement plots and Deming regression plots are shown in Figs. P < 0.001) with LOA of [− 34.9 12.5]. The mean difference in CCT between CASIA SS-1000 and Pentacam was − 10.45 μm (P < 0.001) with LOA of . The differences and LOA increased when the location of measurements was away from the central cornea  and − 0.07 mm (P = 0.004), respectively, and 95% of the differences for TCP(X) were within 0.70 mm, which was smaller than 1.07 mm for TCP(Y)  and CCT/TCT are the most important parameters in making clinical decisions.Anterior curvatures, along with axial length, are the key factors in calculating IOL power. A difference of more than 1 D in anterior corneal curvature is considered as clinically significant. The repeatability and reproducibility were excellent (SDs < 0.3 D). However, the CASIA SS-1000 had a better reproducibility in measuring flat axis (ratio = 0.58). The average difference in AKf and AKs between the two devices was 0.01 D and − 0.02 D, respectively. LOA limits are within 1 D. Thus, the two instruments are substantially equivalent, however, the CASIA SS-1000 had more consistent results.TCT and CCT are important parameters for preoperative refractive surgery screening. In refractive surgery, based on the Munnerlyn formula , every 1CASIA SS-1000 is 4x (repeatability ratio = 0.22–0.24) more precise than Pentacam when repeating TCT and CCT measurements using the same device, and 5x (repeatability ratio = 0.20) more precise than Pentacam when repeating TCT and CCT measurements using different devices.The mean difference in CCT between CASIA SS-1000 and Pentacam of − 10.45 μm  with LOA ranging 45 μm  could be considered clinically significant. This difference may lead ophthalmologists to make a safer (more conservative) decision for refractive surgery. However, it may disqualify some patients who would be qualified if measured by Pentacam. The two measurements can be converted by the following equation: CASIA = 10.87 + 0.97 x Pentacam. For example, an eye measured 500 μm CCT by Pentacam can be converted to CASIA measurement as 490.87 μm. Therefore, decreasing the clinical difference in the values can be obtained. Similarly, TCT measurements can be converted by CASIA = 6.88 + 0.97 Pentacam. However, the decreased variability in measurements obtained with the CASIA SS-1000 results in more consistent clinical decisions.μm), Visante/Stratus , SL-OCT , and specular microscopes (by 20 μm). Other studies showed similar results, with Pentacam overestimating by an average of 17 μm, compared to Visante OMNI  (17.8 ± 11.3 μm) [μm) [In addition, after reviewing 94 papers published between 2000 and 2014, Rozema et al. reported that of the 14 instruments in which Pentacam was compared, five significantly overestimated CCT in normal eyes . These iμm) [μm) .Recent studies have shown that posterior corneal curvature, especially maximal point of elevation over the best-fit reference image, was statistically significant for keratoconus . The abiThe absolute value of the posterior surface being smaller will affect the IOL calculation if the posterior corneal curvature value is used to calculate the total corneal power. However, recent studies using the Barret toric calculator showed that an estimated posterior curvature is just as accurate as a measured corneal curvature when looking at post-cataract refractive outcomes. As the Barrett formula is the current standard for toric IOL calculations, the difference in absolute value measurement of the posterior corneal surface between the Pentacam and CASIA will have little clinical difference in accuracy when correcting astigmatism, as the assumption has shown equivalent results to measured values. The anterior corneal surface measurements between the Pentacam and CASIA, which are more important in corneal measurement when performing IOL calculations, were not statistically different.The corneal thickness and location data has less variability for the CASIA, compared to the Pentacam, in both repeatability and reproducibility. The CASIA corneal thickness measurements are also consistently lower in value than the Pentacam corneal thickness measurement in every point in the periphery: PCT2, PCT4, and PCT6. The pattern/distribution of corneal thickness (pachymetry map) and the location of the thinnest point in the corneal is important in planning for refractive surgery and detecting corneal diseases, such as keratoconus . Thus, lThis paper is the first to compare the inter-user repeatability and inter-device reproducibility of the Pentacam and CASIA SS-1000. The instruments were found to be substantially equivalent for planning IOL implantation surgery. Measurements in corneal thickness, although not identical, can be adjusted by the formula reported herein. Additionally, the variability is considerably less with the CASIA SS-1000 and, thus, offers more consistent results, an important factor in laser refractive surgery.


Despite an increasing number of fragility fractures of the pelvis (FFP) over the last 2 decades, controversy persists on their therapy with special regard to potential complications. Therefore, the present study compared the complication rates and in-hospital mortality of non-operative therapy, percutaneous treatment and open reduction and internal fixation (ORIF) of pelvic fractures in elderly patients.All consecutive patients treated for FFP between January 2013 and December 2017 aged 65 years or older were retrospectively identified from an institutional database. Demographic data and specific patient data were collected with a special focus on pre-existing comorbidities. General and surgical complications, hospital length of stay (LOS) and mortality rates were compared.p = 0.103). Surgery-related complications were twofold more frequent in the ORIF group as than in the percutaneously treated group (18.1% vs. 9.5%). The LOS differed significantly . Hospital mortality rate was higher in patients with ORIF (5.3%) than percutaneous treatment (0%) (p = 0.044).379 patients  were identified, 211 (55.7%) were treated non-operatively, 74 (19.5%) percutaneously and 94 (24.8%) with ORIF. The rate of general complications did not differ between treatment groups (non-operative: 21.8%; percutaneous: 28.4%; ORIF: 33.0%; Complication rates and hospital mortality in elderly patients with FFPs are high and associated with long LOS. For surgical treatment of FFPs, the complication rate and mortality can be significantly reduced using percutaneous procedures compared to ORIF. Therefore, percutaneous surgery should be preferred where possible.The online version contains supplementary material available at 10.1007/s00068-021-01660-w. Despite an increasing number of fragility fractures of the pelvis (FFP) over the last 2 decades –3, contrIn case of unstable fractures or in case of failure of non-operative treatment, surgical stabilization is recommended . In receComplication rates in elderly patients with a pelvic fracture can be up to 58% even with non-operative treatment of supposed simple fractures . Data onTherefore, in this study we compared the complication rates and in-hospital mortality of non-operative therapy and percutaneous surgery and open reduction and internal fixation (ORIF).The present study was approved by the local ethics committee (151/17-ek).All consecutive patients aged 65 years or older treated for FFP were retrospectively identified from an institutional database. According to the inclusion and exclusion criteria, 379 patients were available for evaluation Fig. .Fig. 1StPatients were divided into three groups depending on their treatment: non-operative treatment, percutaneous surgery, and ORIF. Percutaneous surgery was defined as the use of iliosacral/transsacral screws (augmentation was used depending to the surgeon), pubic ramus screws and supraacetabular screws. ORIF included all open approaches  or their combination followed by internal fixation by plates or screws. Spinopelvic fixation was classified as an open method in this study. If only a part of the surgery was performed open, it was considered to belong to the ORIF group.According to our institutional protocol, FFP I and FFP II were managed non-operatively using pain killers and mobilization under physiotherapeutic supervision. In case mobilization failed within 4–5 days, percutaneous surgical treatment or ORIF was performed. FFP III and FFP IV with corresponding symptoms were indicated for surgical therapy if there were no contraindications or the patient refused surgery. All patients were allowed full weight-bearing postoperatively, regardless of treatment.Patient`s demographics and the following comorbidities were recorded: diabetes mellitus; arterial hypertension; chronic heart failure (CHF); chronic obstructive pulmonary disease (COPD); osteoporosis; renal insufficiency; systemic malignancy; and dementia.All fractures were classified according to Rommens and Hofmann with FFP classification and retrospectively verified by the senior author .The following documented acute major complications that required specific treatment were evaluated: pneumonia, acute cardiac event, thromboembolism, stroke, multiple organ failure, systemic inflammatory response syndrome (SIRS), sepsis, and delirium. Treated urinary tract infections (UTI) were not counted as major complications, as there are concerns about the documentation and definition of the attending clinician.Surgical complications documented include the following: unexpected intraoperative bleeding, iatrogenic nerve damage, implant malpositioning, surgical site infections, and implant failure with loss of reduction.In addition, the time to surgery, length of hospital stay (LOS) and mortality were recorded and evaluated.Statistical analyses were performed in SPSS 24.0 . Unless otherwise denoted, data were summarized as mean with standard deviation (SD).U test were used depending on the number of compared groups. The level of significance was defined as p < 0.05.Primary outcome was the occurrence of acute complications during the hospitalization. The hypothesis was that the complication rate as well as LOS and mortality depend on the extent of the surgical therapy. In order to assess possible interfering factors, the baseline characteristics and pre-existing conditions were compared between non-operative, percutaneous and ORIF groups. For all analyzed data, a normal distribution could be determined using the Shapiro–Wilk test. Nominal data were compared with the Chi-square test and for continuous data the Kruskal–Wallis test and Mann–Whitney p < 0.001).Of 379 patients included , 211 (55.7%) were treated non-operatively, 74 (19.5%) percutaneously and 94 (24.8%) with ORIF. Patient’s demographics and their comparison in relation to their treatment group are presented in Table Almost all patients had pre-existing comorbidities (97.6%); significantly different between the groups was the incidence of dementia that correlated with non-operative treatment Table .Table 2PThe distribution of fractures and the treatment of the respective fracture types are shown in Figs. p = 0.103) . Predominant is the difference in the infection rate . In 10/12 patients, the implant was preserved after revision surgery due to infection, two patients received a change from a spinopelvic fixation to sacroiliac screw fixation. Details on the complications are given in Table Surgery-related complications occurred in a total of 15.7% of patients and had a twofold higher incidence in the ORIF group compared to the percutaneously treated group . Preoperative waiting time for percutaneous treated patients was longer than for ORIF , but postoperative hospital stay was distinctly shorter for percutaneously treated patients than for ORIF .The shortest LOS was observed in non-operatively treated patients (8.9 ± 7.1 days), followed by the percutaneously treated (16.6 ± 8.2 days) and the longest remaining were patients with ORIF (19.3 ± 12.8 days) (p = 1.0) overall. Nevertheless, mortality was significantly higher for ORIF (5.3%) compared to percutaneous treatment (0.0%) (p = 0.044).Total hospital mortality rate was 2.9% and there was no difference between non-operative (2.8%) and operative treatment (3.0%) . However, younger and multiple injured patients were included from Ochenjele et al. limiting the comparison . Data onAs previously published, we also found a prolonged inpatient stay with a maximum for ORIF of almost 20 days on average , 16. FroThe in-hospital mortality rate of 2.9% also corresponds to previous reports (1.3–7.6%) , 23, 24.In a recent registry study “general health” was frequently stated as a reason for non-operative treatment and thus influences the surgeons decision . The preSeveral limitations to the present study must be stated. Due to the retrospective nature of the study, no statement about the treatment decision is possible. Certainly, there is a bias in this examination, as the decision on therapy also depends on comorbidities in individual cases. It is well known that besides chronological age, biological age and activity level of the patients affect the therapy decisions. To be able to compare this more objectively, a validated frailty index should be used in prospective studies.Not every patient can be treated non-operatively due to persistent pain and immobilization. As is well known, persistent immobilization increases the risk of other complications such as thrombosis, pneumonia, pressure ulcerations, etc. , 28–30. Another weakness of this study is the lack of follow-up after discharge. Especially for FFP, we know that it can be a creeping process and a fracture successfully treated non-operatively at the beginning can also worsen and require surgical treatment later on , 17, 32.Inpatient complication rates in elderly patients with FFP are high and associated with prolonged LOS.In case of operative treatment of FFP in elderly patients with existing comorbidities, the complication rate and mortality can be significantly reduced using percutaneous procedures instead of ORIF. Therefore, a percutaneous procedure should be preferred whenever possible.Supplementary file1 (DOCX 14 KB)Supplementary file2 (DOCX 27 KB)Below is the link to the electronic supplementary material.


Solanum hjertingii is a wild tuber-bearing species classified in the Solanaceae family. The chloroplast genome of S. hjertingii was completed via de novo assembly using Illumina paired-end sequencing data. Total length of the chloroplast genome of S. hjertingii is 155,545 bp consisting of 85,976 bp in a large single copy, 18,383 bp in a small single copy, and 25,593 bp in a pair of inverted repeat regions. Its structure is circular and typically quadripartite. It contains 158 predicted genes in total, including 105 protein-coding, 45 tRNA, and eight rRNA genes. Maximum likelihood phylogenetic analysis of the sequence along with 33 species in the Solanaceae family revealed that S. hjertingii belongs to a large clade with other Solanum species including S. tuberosum and is most closely grouped in the clade with S. hougasii and S. stoloniferum in the clade. Solanum hjertingii Hawkes 1963 is a relative of the potato (Solanum tuberosum) originating from Mexico. It has been identified as a potential source of resistance to blackspot bruising because it exhibits neither enzymatic browning nor blackspot caused by impact or compression damage during harvest or storage . For these reasons, the wild species can be used for introgression of certain traits into the cultivated potatoes. However, S. hjertingii and S. tuberosum are not conventionally crossable, although both are tetraploids. The endosperm balance numbers (EBNs) for these species are 2 and 4, respectively  was obtained from the Highland Agriculture Research Institute, South Korea (37^68′05.4″N 128^73′09.1″E) and the specimen deposited at the National Agrobiodiversity Center, South Korea  as voucher number IT301488. Chloroplast genome sequencing was performed via the Phyzen bioinformatics pipeline . An Illumina paired-end (PE) genomic library was constructed with the genomic DNA by following the PE standard protocol  and was sequenced at Macrogen (http://www.macrogen.com/kor/) using an Illumina HiSeq2000 platform. Approximately 1.48 Gbp of the sequence raw data obtained in total was trimmed and low-quality bases with a raw Phred score of 20 or less were removed using the CLC quality trim program in the CLC assembly cell package version 4.2.1 . Finally, approximately 1.27 Gbp of high-quality PE reads were applied for de novo assembly using the CLC de novo assembly program in the same package followed by retrieving the principal contigs representing the chloroplast genome and arranging the representative chloroplast contigs using Nucmer  is 155,545 bp consisting of a large single copy (LSC) region of 85,976 bp, a small single copy (SSC) region of 18,383 bp, and a pair of inverted repeat (IRa and IRb) regions of 25,593 bp with the typical circular and quadripartite structure like most plastids. Overall GC content was 37.88%. The closest Solanum species were S. hougasii (MF471372) and S. stoloniferum  for S. hougasii (Spooner et al. Results from phylogenetic analysis revealed that oniferum . These roniferum . Their g


The effective dose was 0.19 (0.14–0.31) mSv. Fluoroscopy time was higher in patients with collateral veins (41 (26–49) s vs. 36 (31–61) s, p = 0.02). The median amount of sclerosing agent (SA) used was 3 (3–4) ml. DAP was higher when SA > 3 mL was used (101.4 (65–183) cGy*cm2 vs. 80.5 (59–119) cGy*cm2; p < 0.01). At univariable linear regression, age, BMI, operative time and SA > 3 mL were associated with higher DAP . At multivariable linear regression, only BMI  and operative time  emerged as predictors of higher DAP, after accounting for age and SA > 3 mL. Conclusions: The Tauber procedure is safe and associated with low effective doses. Operative time and the patient’s BMI independently predict a higher radiation dose.Introduction: Antegrade sclerotherapy (Tauber) effectively treats varicocele. However, fluoroscopy exposes young males to ionizing radiation. We aimed to evaluate radiation exposure and surgical outcomes after the Tauber procedure. Materials and methods: We retrospectively analysed data from 251 patients. Dose area product (DAP) and fluoroscopy time were recorded. The effective dose was calculated with the PCXMC software. Descriptive statistics and linear regression tested the association between clinical predictors and radiation exposure. Results: Median (IQR) age and body mass index (BMI) were 14 (13–16) years and 20.1 (17.9–21.6) kg/m². Five (2.1%) patients developed clinical recurrence and two (0.81%) developed complications. Median fluoroscopy time and DAP were 38.5 (27.7–54.0) s and 89.6 (62.5–143.9) cGy*cm Varicocele is a common condition characterised by the abnormal dilation of pampiniform plexus veins due to venous reflux. It becomes more frequent with puberty, reaching a prevalence of 10–15% among adolescents . The exaOver the years, microsurgical varicocelectomy, together with laparoscopic-assisted and even robotic approaches were described to achieve these goals ,7,8. SimMoreover, to the best of our knowledge, no study has ever provided detailed quantitative measures of radiation doses received by the patient during the procedure in the paediatric population. Therefore, in this article, we aimed to assess and correlate surgical outcomes and radiation exposure in paediatric patients submitted to fluoroscopy-guided antegrade sclerotherapy for the treatment of varicocele. We performed a retrospective analysis of data collected from 251 young males affected by varicocele and treated with antegrade sclerotherapy at a single tertiary referral centre between January 2010 and December 2021. Clinical data, perioperative characteristics and surgical outcomes were recorded for all patients. Varicocele diagnosis was based on the physical examination with or without ultrasound assessment. Indications for treatment were the presence of testicular asymmetry and/or symptomatic clinical grade III varicocele. All treated varicoceles in our cohort were left-sided. Aethoxysklerol or Fibrovein) is then mixed with air to make a foam and is immediately injected into the spermatic vein under fluoroscopic vision. This allows for modulating the amount of sclerosing agent which is injected until the complete disappearance of the contrast medium is clearly seen on the C-arm monitor. The cannula is then removed carefully, avoiding any spillage around the site of the entrance by a normal saline flush. The vein is ligated cranially and caudally, and fascia, subcutaneous tissue and skin are closed with absorbable sutures. All patients underwent a routine clinical visit seven days post-operatively and were instructed to report any complication or deviation from a normal postoperative course . Clinical recurrence was evaluated at least one month after surgery. Recurrence was assessed clinically by physical examination with or without ultrasound evaluation.All surgeries were performed under spinal, local or general anaesthesia, as per the patient and/or anaesthesiologist’s preference. A wide-spectrum antibiotic prophylaxis was administered before surgery. To perform the procedure, the patient is positioned in the supine position. A 3–4 cm incision at the scrotal root level is performed. After opening the scrotum, the pampiniform plexus veins are identified and the most dilated and straight vessel is selected, isolated and prepared for cannulation. The venous catheter employed is a 20–24 G, 7 cm long, hollow, flexible and transparent cannula with an oblique cut ending that is inserted in the selected vein. After assessing the patency of the vein by irrigating with saline, the fluoroscopic C-arm is positioned and a contrast agent is injected to allow for visualization of the spermatic vein up until its convergence with the renal vein. The sclerosing agent , always used in automatic modality, mostly with 12.5 pulses/s. The X-ray tube was placed in an undercouch position, X-ray field collimation was adjusted by the radiographer and the image intensifier was as close as possible to the patient body. 2) and is defined as the incident dose multiplied by the beam area. It is typically measured by a DAP meter located between the X-ray source and the patient, usually calculated and displayed by the X-ray system and stored in the DICOM header in order to be retrieved.Fluoroscopy time was recorded for each patient. We investigated two different exposure parameters, namely the Dose Area Product (DAP) and the Effective Dose (ED). DAP is expressed in centigrade per centimeter squared (cGy*cmThe ED expressed in millisieverts (mSv) is calculated for the whole body by adding up the equivalent doses to every organ, each multiplied by a specific tissue weighing factor, therefore taking into account the different radiation sensitivities of different organs in the body. To be noticed, the ED is calculated to a reasonable approximation by means of the PCXMC software, which uses a Monte Carlo method . In partThe Effective Dose provides an overall estimate of radiation exposure, and its use has two main advantages. First, it represents the indicator that most directly correlates to the radiation risk to which patients are subjected. Second, ED calculations can be reported as a point of comparison for a variety of different interventional radiology procedures. Therefore, ED can be easily used to compare radiation exposures in a plethora of settings, allowing physicians to better comprehend the real impact of radiation on the patient during Tauber procedures.Data collection followed the principles outlined in the Declaration of Helsinki. All patients signed an informed consent agreeing to share their own anonymous information for future studies. The study was approved by our hospital Ethical Committee (Prot. 2021-ESQLFDI).p < 0.05. Data distribution was tested with the Shapiro–Wilk test. Data are presented as medians  or frequencies (proportions). Descriptive statistics were used to describe the whole cohort. Univariable (UVA) and multivariable (MVA) linear regression analyses tested the association between clinical predictors and measures of radiation exposure. Statistical analyses were performed using SPSS v.26 . All tests were two-sided and the statistical significance level was determined at 2, respectively. The volume of the affected testicles was reduced in 179 (71.3%) children. The median operative time was 35 (25–41) min and the fluoroscopy time was 35 (30–45) s. Collateral veins were found in 114 (45.4%) cases and sclerosing agents (SA) used were Aethoxysklerol and Fibrovein in 117 (46.6%) and 134 (53.4%) children, respectively. The median amount of SA used was 3 (3–4) mL. Above all, the median (IQR) patient’s age and body mass index (BMI) were 14 (13–16) years and 20.1 (17.9–21.6) kg/m2, respectively, with an effective dose of 0.19 (0.14–0.31) mSv. Fluoroscopy time was higher in patients with collateral veins than those without (41 (26–49) s vs. 36 (31–61) s, p = 0.02). DAP was higher in cases where >3 mL of SA were used (101.4 (65–183) cGy*cm2 vs. 80.5 (59–119) cGy*cm2; p < 0.01). At Spearman’s correlation, the patient’s BMI  and operative time  were positively correlated with higher DAP.p < 0.01). At multivariable linear regression analysis, only BMI  and operative time  emerged as predictors of higher DAP, after accounting for age and >3 mL of SA used  only underwent an immediate post-operative evaluation seven days post-op and were lost to longer-term clinical follow-up and/or did not undergo a post-operative US, which may lead to an underestimation of recurrence rates among our cohort. As already mentioned , howeverAntegrade sclerotherapy is a safe and effective technique for the treatment of paediatric varicocele. Although often criticised for its radiation burden, our study is the first to provide an accurate evaluation of radiation exposure during Tauber procedures. According to our findings, radiation doses during the procedure are minimal and independently predicted by operative time and the patient’s BMI. Varicocele becomes increasingly common during puberty and often becomes a major fertility issue when patients become young adults. Adequate prevention is paramount and antegrade sclerotherapy should be considered an appropriate option for the treatment of varicocele in the paediatric population.


Tuberculous peritonitis (TBP) is a rare but fatal complication in patients on peritoneal dialysis (PD). In this study, we aimed to determine the demographic features, clinical features, laboratory parameters, and clinical outcomes of PD patients with TBP and to clarify possible risk factors for mortality.Mycobacterium tuberculosis.We retrospectively reviewed 2084 PD patients from January 1985 to December 2019. The diagnosis of TBP was established by positive peritoneal fluid culture for p = 0.040), the presence of diabetes mellitus (p = 0.024), and PD catheter removal (p < 0.001) between TBP patients with and without mortality. However, none of them was a significant factor for 1-year mortality in multivariate Cox regression model.18 patients were diagnosed with TBP. The incidence was 2.029 episodes per 1000 patient-years. The most common symptom was fever (94.4%), followed by cloudy effluent (83.3%) and abdominal pain (83.3%). The average peritoneal dialysis effluent (PDE) white blood cell (WBC) count was 172.7 cells/μL. Nine patients (50%) had WBC counts lower than 100 cells/μL and 13 patients (72.2%) had neutrophilic predominant WBC counts. Acid fast stain (AFS) was positive in 7 patients (38.9%). Only 2 patients (11.1%) continued with PD after TB infection, while 10 patients (55.6%) changed to hemodialysis. Seven patients (38.9%) died within 1 year. Significant differences were observed in sex (Physicians should pay attention to the unusual presentations of peritonitis, especially if symptoms include fever or an initial low PDE WBC count. Catheter removal is not mandatory if early diagnosis and appropriate therapy are available. According to the 2021 United States Renal Data System (USRDS) annual report, Taiwan had the greatest prevalence (3679 per million population) and the top 2 incidences (529 per million population) of end-stage renal disease (ESRD) in 2019 . PeritonTuberculosis (TB) is an ancient disease that is most prevalent in developing regions, such as Southeast Asia, Africa and the western Pacific region . Taiwan In this study, we aimed to provide our thirty-five year experience of observing PD patients with TBP at Linkou Chang Gung Memorial Hospital (CGMH), and we aimed to determine the varying demographic features, clinical features, laboratory parameters, and clinical outcomes of PD patients with TBP and to clarify possible risk factors for mortality.This observational cohort study was performed in accordance with the guidelines of the Declaration of Helsinki. Ethics approval  was obtained from the Institutional Review Board of Chang Gung Medical Foundation in Taiwan without the requirement for a patient consent form because the study was a retrospective review. All the information was anonymized, delinked, and accessible only to the investigator. Finally, all primary data were collected in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.3 (or 0.1 x 109/L after a dwell time of at least two hours), with > 50% neutrophils, and (3) positive dialysis effluent culture [Mycobacterium tuberculosis (MTB). The definite diagnosis of TBP in our study was established only by positive peritoneal fluid culture for MTB.In our retrospective cohort study, we initially reviewed 2084 PD patients at Linkou CGMH over a period of 35 years (from January 1985 to December 2019). Peritonitis was diagnosed when the patient met at least two out of the following three characteristics: (1) consistent clinical features, including abdominal pain or cloudy effluent, (2) peritoneal fluid white blood cell (WBC) count greater than 100/mmWe included baseline demographic features, including sex, age, body mass index (BMI), the cause of ESRD, PD modality (automated PD or continuous ambulatory PD), the duration of PD at enrollment in the study, the presence of diabetes mellitus (DM), and residual urine volume. The clinical features included fever, cloudy effluent, abdominal pain, previous episodes of peritonitis, extraperitoneal TB, and the time from diagnosis to treatment initiation (days). The laboratory parameters included peritoneal dialysis effluent (PDE) features with WBC count, including the percentage of neutrophils and lymphocytes, red blood cell (RBC) count, AFS smear, PCR and culture for MTB, as well as blood analysis with WBC count, hemoglobin (Hb), platelet (PLT) count, C-reactive protein (CRP), blood urea nitrogen (BUN), creatinine, and albumin.p-values were two-tailed, and a p-value < 0.05 was considered statistically significant. All analyses were performed with PASW Statistics for Windows version 18.0 .Continuous variables are listed as the mean ± standard deviation (SD). Categorical variables are listed with numbers and percentages. To compare the 2 groups, we used the Mann–Whitney U test to analyze continuous variables and the chi-square test to analyze categorical variables. Univariate Cox regression analysis was used to compare the frequencies of possible risk factors for 1-year mortality. All p = 0.048) was a significant risk factor for 1-year mortality  experienced at least one episode of peritonitis between January 1985 and December 2019. There were 1996 reported episodes of peritonitis, including bacterial (64.13%), fungal (3.36%), tuberculous (0.90%), nontuberculous mycobacterial (0.20%), polymicrobial (7.31%), and culture-negative (24.10%). The cumulative follow-up of all 2084 patients was 106446.9 months. The incidence of all peritonitis was 0.2250 episodes per patient-year, and the incidence of TBP was 2.029 episodes per 1000 patient-years. During the follow-up period, only 18 patients had TBP episodes. The demographic and clinical features are shown in ortality . 4 imporA computerized PUBMED review of the English-language literature from January 1990 through June 2022 identified a total of 10 retrospective studies (including 7 single-center and 3 multicenter studies) of PD patients with TBP ,21–24 T. The meaTo the best of our knowledge, our study is the longest follow-up study about PD patients with TBP in the literature. We provided our single-center experience and performed a literature review of PD patients with TBP.The diagnosis of TBP is challenging due to its similarities with other diseases, lack of specificity of symptoms, artificial factors of culture, etc ,25,26.. It is worth mentioning that there were some confusing situations in predicting TBP by the white cell count and differential in the dialysis effluent. In our patients, the average PDE WBC count was 172.7 ± 153.6 cells/μL. However, 9 out of the 18 patients’ WBC counts were lower than 100 cells/μL, with the lowest count being 10 cells/μL. Therefore, TB PCR should be considered when PD patients initially have clinical features of peritonitis with a low dialysis effluent white cell count.Although we already know that PD patients are exposed to the risk of TBP in TB-endemic regions, the exact incidence data are limited. In our series, the incidence of TBP was 2.029 episodes per 1000 patient-years with a follow-up period of 35 years. In an earlier study, the incidence of TBP among patients under PD was 5–15 times higher than that in the general population ,19. In tp = 0.04), which indicates that TBP may be more fatal in female PD patients. However, Cox regression analysis demonstrated that sex  was not a significant risk factor for 1-year mortality. The significant sex difference in mortality may be due to age . Concerning sex, Kang-Ju Chou et al. also reported that the risk of TB infection in CAPD was 11 times higher in females than in males [In previous literature, the mortality of PD patients with TBP has been reported to range from 18 to 58% ,21,23,24p = 0.024). This is reasonable because DM is related to impaired cellular immunity, which contributes to higher morbidity and mortality of TB infection [p = 0.050) was almost a significant risk factor for 1-year mortality. Extraperitoneal TB was seen in 2 of the 18 patients, with one who survived and one who expired but with an insignificant outcome (p = 0.732). The previous studies did not mention the mortality of TBP of superimposed extraperitoneal TB.Significant differences in mortality were also observed between the patients with or without DM  was not a significant risk factor for 1-year mortality. The discrepancy may be related to female sex , age , the presence of DM  rather than the mean treatment initiation delay  between patients with or without catheter removal. In A. Waness’s study, 4 PD patients with TBP received catheter removal intervention, and all patients survived for 3 years [Catheter removal has long been a controversial issue in PD patients with TBP. In our study, 10 patients who underwent catheter removal all transferred to HD, and they all lived. Eight patients did not have their catheters removed, 6 died before continuation, 1 died after continuation, and 1 lived after continuation. It seems that catheter removal after a diagnosis of TBP benefits patient survival. However, Cox regression analysis demonstrated that catheter removal  in our hospital [This study has some limitations. First, this study provides only a single-center experience, and the analysis of multiple center data is needed. Second, two different methods for isolating microorganisms from PDE were used during this study (before and after 1996). The incidence of culture-negative peritonitis (CNP) decreased significantly after changing the culture method in 1996 (35.7 versus 20.7%, hospital . The incIn conclusion, the diagnosis of TBP is challenging. The physician should pay more attention to any unusual presentation of peritonitis, especially fever or an initial low PDE WBC count. We suggest that AFS should be performed initially in each patient with peritonitis despite its low sensitivity, and TB PCR should be considered within the initial 5 days if the patient has a poor response to the empiric antibiotics used. Catheter removal is not mandatory if early diagnosis and appropriate therapy are available.


Pregnancy-induced hypertension syndrome (PIH) is a common pregnancy syndrome that could cause varying degrees of maternal and fetal organic damage and even endanger their lives. This study aimed to investigate ultrasound of fetal cardiac function changes in PIH. Totally 40 cases of gestational hypertension admitted to Cangzhou Central Hospital between October 2018 and September 2019 were enrolled in the hypertension group, and 40 women with healthy pregnancies during the same period were assigned to the normal group. Ultrasound results showed that PIH was associated with a significantly higher fetal cardiac septal thickness, fetal left ventricular end-diastolic area and end-systolic area, fetal right ventricular end-diastolic area and end-systolic area, fetal left ventricular systolic fraction 1 (VSF1), fetal left ventricular systolic fraction 2 (VSF2), fetal right VSF1, and fetal right VSF2 versus healthy pregnancy. The PIH fetuses had significantly lower neonatal weights versus healthy fetuses. Newborns of hypertensive pregnancies have larger hearts, faster heart rates, increased cardiac contractility, and lower weights versus newborns of healthy pregnancies. Pregnancy-induced hypertension syndrome (PIH) is a common pregnancy syndrome that could cause varying degrees of maternal and fetal organic damage and even endanger their lives , 2. Its Due to the unknown etiology of PIH, the treatment mostly relies on spasm lysis, hypotension, diuresis, and timely termination of pregnancy according to its predisposition factors and pathophysiological changes. This disease seriously compromises maternal and child health and is one of the leading causes of morbidity and mortality in pregnant women and perinatal children. Therefore, early detection and assessment of fetal cardiac function are paramount to guide clinical assessment of the condition for further treatment . EchocarThe present study was conducted to compare the cardiac function of fetuses of PIH with those of normal pregnancy through ultrasound to investigate the diagnostic value of ultrasound for PIH on fetal cardiac function changes and its significance for clinical reference.Between October 2018 and September 2019, 40 cases of PIH admitted to our institution were assessed for eligibility and recruited in the hypertension group, and 40 women with healthy pregnancies during the same period were assigned to the normal group. All 80 cases in both groups were singleton fetuses with no malformations after examinations. The study was ethically approved by the Ethics Committee of Cangzhou Central Hospital (2018-JY225).It includes (a) patients with singleton pregnancies; (b) patients with PIH who met the diagnostic criteria of the syndrome in the hypertension group; (c) patients with normal communication skills; and (d) patients with knowledge and consent to the study content.It includes (a) patients with fetal malformations; (b) patients with fetuses with congenital heart disease; and (c) patients with abnormal liver and kidney functions.Fetal biparietal diameter, head perimeter, femoral length, amniotic fluid index, and placenta condition were measured.The fetal spine, liver, and gastric vesicles were identified as the left and right ventricles of the heart. The thickness of the diastolic interventricular septum (IVS) was measured under a four-chamber heart view. The left ventricular end-systolic perimeter and area , right ventricular end-systolic perimeter and area , and right and left ventricular end-diastolic perimeter and area  were measured as per the different phases of the heart and playback function.Ventricular systolic fraction 1 (VSF1) = (ventricular end-diastolic perimeter−ventricular end-systolic perimeter)/ventricular end-diastolic perimeter. Ventricular systolic fraction 2 (VSF2) = (ventricular end-diastolic area−ventricular end-systolic area)/ventricular end-diastolic area.s) and processed using independent samples t-test. The count data were expressed as  and analyzed using the chi-square test. Differences were considered statistically significant at P < 0.05.SPSS 20.0 was used for data analyses, and GraphPad Prism 8 was used for image rendering. The measurement data were expressed as (P > 0.05)  were comparable with those of the normal group  ( > 0.05) .P < 0.05). PIH exerts a greater effect on the right cardiac system than on the left cardiac system  , the FVSF2 was (0.38 ± 0.15), the RVSF1 was (0.24 ± 0.03), and the RVFS2 was (0.35 ± 0.08), while the above indicators were (0.13 ± 0.04), (0.20 ± 0.09), (0.16 ± 0.10), and (0.21 ± 0.14) in the normal group. The systolic fractions of both the left and right ventricles were significantly higher in the fetuses of the hypertension group versus those of the normal group ( < 0.05) .g and that of the newborns in the normal group was (3486 ± 589) g. PIH newborns showed significantly lower neonatal weights versus healthy newborns (P < 0.05) (The weight of the newborns in the hypertension group was (3036 ± 761)  < 0.05) .The results of the present study showed a significantly higher fetal ventricular systolic and diastolic perimeter and area and septal thickness in the hypertension group than in the normal group, which indicates that maternal hypertension in pregnancy may seriously compromise the fetal cardiac function. Meanwhile, PIH causes a greater impact on the fetal right heart system than the left heart system, suggesting a larger right heart system than the left heart system in fetuses of PIH , 11. In PIH is a syndrome specific to pregnant women , 17 and The PIH fetuses had significantly lower neonatal weights versus healthy fetuses. Newborns of hypertensive pregnancies have larger hearts, faster heart rates, increased cardiac contractility, and lower weights versus newborns of healthy pregnancies.