Prevalence,morphology, and molecular analysis of Serrasentis sagittifer (Acanthocephala: Palaeacanthocephala: Rhadinorhynchidae), a parasite of the gilthead Sea bream Sparus aurata (Sparidae)

Seventy specimens of the gilthead sea bream Sparus aurata of the Red Sea were collected during the period from March to November 2013; they were dissected and examined for parasitic acanthocephalans. Only 40 (57.14 %) specimens were found to be naturally infected with Serrasentis sagittifer belonging to family Rhadinorhynchidae. The infection was recorded in the intestine, pyloric ceca, and the external surfaces of some internal organs of the infected fish. Seasonally, the prevalence of infection was increased to 77.14 % during summer season and decreased to 37.14 % during winter. Light and scanning electron microscopic investigation revealed that the adult worm was elongated (with broad anterior and narrow posterior ends) and measured 6.9–8.6 (7.6?±?0.2)?×?0.57–0.73 (0.63?±?0.02) mm for male and 10.2–12.1 (11.5?±?0.2)?×?0.71–0.82 (0.76?±?0.02) mm for female. Proboscis was long and cylindrical with a length of 0.97–1.6 mm (1.2?±?0.2) for male and 1.12–1.17 mm (1.14?±?0.02) for female. It was covered with numerous uniform spines arranged longitudinally as 9–11 rows each equipped by 15–18 spines. Spines were triangular, arrow-shaped, strong, and covered with cuticular theca; they decreased in size from the apex to the base of the proboscis. The proboscis is followed by a short spineless neck region followed by the body proper which is supported by multiple combs of spines (16–20) on its ventral surface. Molecular analysis of 18S rDNA sequence for the parasite demonstrated a close identity (>83 %) between the present acanthocephalan and other previously described species within class Palaeacanthocephala with 98 % identity with the previously recorded S. sagittifer (acc. no. JX014227) which is supported by the morphological data and the presence of trunk spines arranged within rows (comb-like) and the presence of four cement glands in the males. So, according to the records of morphological and molecular analyses, the present parasite is classified as S. sagittifer belonging to class Palaeacanthocephala and family Rhadinorhynchidae with a new host record from the gilthead sea bream S. aurata of the Red Sea.     

Interactions between killer immunoglobulin-like receptors and their human leucocyte antigen Class I ligands influence the outcome of unrelated haematopoietic stem cell transplantation for thalassaemia: a novel predictive algorithm

In a study conducted on 114 patients undergoing unrelated donor haematopoietic stem cell transplantation (HSCT) for thalassaemia, we observed that the lack of activating killer immunoglobulin-like receptors (KIRs) on donor natural killer (NK) cells significantly increased the risk of graft-versus-host disease (GvHD) [hazard risk (HR) 4.2, 95% confidence interval (CI) 1.7-10.1, P = 0.002] and transplantation-related mortality (HR 4.7, 95% CI 1.6-14.2, P = 0.01). The risk of GvHD furthermore increased when recipients heterozygous for HLA-C KIR ligand groups (C1/C2) were transplanted from donors completely lacking activating KIRs (HR 6.1, 95% CI 1.9-19.2, P = 0.002). We also found that the risk of rejection was highest when the recipient was homozygous for the C2 HLA-KIR ligand group and the donor carried two or more activating KIRs (HR 6.8, 95% CI 1.9-24.4, P = 0.005). By interpolating the number of donor activating KIRs with recipient HLA-C KIR ligands, we created an algorithm capable of stratifying patients according to the immunogenetic risk of complications following unrelated HSCT. In clinical practice, this predictive tool could serve as an important supplement to clinical judgement and decision-making.     

The loss of extension test (LOE test): a new clinical sign for the anterior cruciate ligament insufficient knee

Background

This prospective study was created to evaluate the reliability of a new clinical test, which we termed the “loss of extension test” (LOE test). The LOE test investigates the loss of normal maximum passive extension (MPE) of the knee due to an anterior cruciate ligament tear in comparison to the normal MPE of the healthy knee.

Materials and methods

The study was divided into two consecutive parts. Part 1 was designed to assess the side-to-side difference in normal MPE in a healthy population. In part 1, 100 healthy adults were enrolled. Part 2 was designed to evaluate the LOE test reliability in injured knees. In part 2, we included 196 selected patients.

Results

In part 1, the average side-to-side difference in MPE in the healthy population was not statistically significant. In part 2, the overall average side-to-side difference in MPE of the injured group was 10.1 mm ± 14.1 (min −20; max 60), which was not statistically significant (p = 0.52). An anterior cruciate ligament (ACL) tear was found in 121 knees among 196 patients. The average side-to-side difference in MPE in the ACL-insufficient group was 16.9 mm ± 13.4 (min −20; max 60), which was statistically significant (p < 0.0001). The accuracy of the loss of extension test was 83.7 %, its specificity was 93.3 %, its sensitivity was 77.7 %, its positive predictive value was 95 %, and its negative predictive value was 72.2 %.

Conclusions

The reliability of the LOE test is comparable to those reported in the literature for the Lachman test and dynamic tests, so the LOE test could represent a useful tool for the diagnosis of the anterior cruciate ligament insufficient knee.     

Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained

Key points

• Aerobic exercise, such as running, enhances adult hippocampal neurogenesis (AHN) in rodents.
• Little is known about the effects of high‐intensity interval training (HIT) or of purely anaerobic resistance training on AHN.
• Here, compared with a sedentary lifestyle, we report a very modest effect of HIT and no effect of resistance training on AHN in adult male rats.
• We found the most AHN in rats that were selectively bred for an innately high response to aerobic exercise that also run voluntarily and increase maximal running capacity.
• Our results confirm that sustained aerobic exercise is key in improving AHN.

Abstract

Aerobic exercise, such as running, has positive effects on brain structure and function, such as adult hippocampal neurogenesis (AHN) and learning. Whether high‐intensity interval training (HIT), referring to alternating short bouts of very intense anaerobic exercise with recovery periods, or anaerobic resistance training (RT) has similar effects on AHN is unclear. In addition, individual genetic variation in the overall response to physical exercise is likely to play a part in the effects of exercise on AHN but is less well studied. Recently, we developed polygenic rat models that gain differentially for running capacity in response to aerobic treadmill training. Here, we subjected these low‐response trainer (LRT) and high‐response trainer (HRT) adult male rats to various forms of physical exercise for 6–8 weeks and examined the effects on AHN. Compared with sedentary animals, the highest number of doublecortin‐positive hippocampal cells was observed in HRT rats that ran voluntarily on a running wheel, whereas HIT on the treadmill had a smaller, statistically non‐significant effect on AHN. Adult hippocampal neurogenesis was elevated in both LRT and HRT rats that underwent endurance training on a treadmill compared with those that performed RT by climbing a vertical ladder with weights, despite their significant gain in strength. Furthermore, RT had no effect on proliferation (Ki67), maturation (doublecortin) or survival (bromodeoxyuridine) of new adult‐born hippocampal neurons in adult male Sprague–Dawley rats. Our results suggest that physical exercise promotes AHN most effectively if the exercise is aerobic and sustained, especially when accompanied by a heightened genetic predisposition for response to physical exercise.

Abbreviations

AHN

adult hippocampal neurogenesis

BDNF

brain‐derived neurotrophic factor

BrdU

bromodeoxyuridine

HIT

high‐intensity interval training

HRT

high‐response trainer

LRT

low‐response trainer

RW

running wheel

Sed

sedentary

TBS

Tris‐buffered saline

V˙O2max

maximal oxygen uptake

     

Integrative genetic, epigenetic and pathological analysis of paraganglioma reveals complex dysregulation of NOTCH signaling

Head and neck paragangliomas, rare neoplasms of the paraganglia composed of nests of neurosecretory and glial cells embedded in vascular stroma, provide a remarkable example of organoid tumor architecture. To identify genes and pathways commonly deregulated in head and neck paraganglioma, we integrated high-density genome-wide copy number variation (CNV) analysis with microRNA and immunomorphological studies. Gene-centric CNV analysis of 24 cases identified a list of 104 genes most significantly targeted by tumor-associated alterations. The “NOTCH signaling pathway” was the most significantly enriched term in the list (P = 0.002 after Bonferroni or Benjamini correction). Expression of the relevant NOTCH pathway proteins in sustentacular (glial), chief (neuroendocrine) and endothelial cells was confirmed by immunohistochemistry in 47 head and neck paraganglioma cases. There were no relationships between level and pattern of NOTCH1/JAG2 protein expression and germline mutation status in the SDH genes, implicated in paraganglioma predisposition, or the presence/absence of immunostaining for SDHB, a surrogate marker of SDH mutations. Interestingly, NOTCH upregulation was observed also in cases with no evidence of CNVs at NOTCH signaling genes, suggesting altered epigenetic modulation of this pathway. To address this issue we performed microarray-based microRNA expression analyses. Notably 5 microRNAs (miR-200a,b,c and miR-34b,c), including those most downregulated in the tumors, correlated to NOTCH signaling and directly targeted NOTCH1 in in vitro experiments using SH-SY5Y neuroblastoma cells. Furthermore, lentiviral transduction of miR-200s and miR-34s in patient-derived primary tympano-jugular paraganglioma cell cultures was associated with NOTCH1 downregulation and increased levels of markers of cell toxicity and cell death. Taken together, our results provide an integrated view of common molecular alterations associated with head and neck paraganglioma and reveal an essential role of NOTCH pathway deregulation in this tumor type.