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Ornithine transcarbamylase deficiency (OTCD) is the most common X-linked hereditary disorder of urea cycle disorders that is caused by neonatal hyperammonemia. OTC gene sequence variations are common causes of OTCD. The current study presents a 28-month-old baby girl proband with phenotypical characteristics of OTCD such as irritability, somnolence, intermittent vomiting, and high levels of serum ammonium. Whole-exome sequencing revealed a de novo c.275G>A p.(Arg92Gln) variant within the OTC gene. In silico analysis revealed a possible differential affinity between wild-type and mutant OTCase, while Arg92Gln decreases the binding ability of OTCase to the substrate, which can disrupt the urea cycle and explains the molecular pathogenicity of clinical hyperammonemia. In light of the fact that the genotype and phenotype correlation of OTCD is still uncertain, the present in silico analysis outcome can enhance our knowledge on this complicated, rare, and severe genetic disorder., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of the study was to evaluate the effect of lower limb strengthening and balance exercises on balance, quality of life and neuropathic pain of the cancer patients receiving neurotoxic chemotherapy., Design: Patients who were planning to receive neurotoxic chemotherapy agents were included in the first group. They were trained before the neurotoxic chemotherapy sessions with the 10-wk home-based exercise program including lower limb strengthening and balance exercises. The second group of patients who had received the third cycle of neurotoxic chemotherapy had no exercise program. Both groups were evaluated after the third cycle. Neurocom Balance Master and Berg Balance Scale were used to evaluate balance. The neuropathic pain was questioned by PainDETECT questionnaire and the quality of life was assessed with the European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire., Results: Sixty patients were admitted to this study. Twenty-four patients were in the exercise group (F = 14, M = 10) and 36 patients were in the control group (F = 17, M = 19). Sociodemographic and clinical data of both groups were similar. Berg Balance Scale (P = 0.005), European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire global quality of life, physical function, and emotional status were higher, and symptom scores and PainDETECT questionnaire score were lower in the exercise group (P < 0.05). Balance tests were different between the groups., Conclusions: Strengthening and balance exercises have a valuable effect on balance, quality of life, and neuropathic pain in patients receiving neurotoxic chemotherapy.

Objectives: To perform a systemic investigation on oxidative stress and DNA damage in patients with primary pterygium., Methods: This prospective cross-sectional study included 32 patients with primary pterygium (60.1±2.0 years of age) and 33 age- and sex-matched (58.8±2.2 years of age) control subjects (P>0.05). A commercial kit was used for measuring serum total oxidant status (TOS) and total antioxidant status (TAS). The comet assay was performed after lymphocyte isolation from venous blood to quantitate DNA damage. Tail length (TL), tail intensity (TI), and tail moment (TM) were used for statistical analysis as parameters of DNA damage., Results: In the pterygium group, TOS and TAS were significantly higher when compared with those of the control group (P=0.019 and P=0.005, respectively). In terms of DNA damage, patients with pterygium had higher TL, TI, and TM than in the control subjects (P<0.0001 for all)., Conclusions: Although current literature focuses on local factors in pterygium pathogenesis, patients with pterygium seem to have increased systemic oxidative status (and compensatory antioxidant response) and genotoxicity, which might create a predisposition for pterygium development.

Background and Purpose: Reperfusion is the most significant determinant of good outcome after ischemic stroke. However, complete reperfusion often cannot be achieved, despite satisfactory recanalization. We hypothesized that microvascular protection was essential for achieving effective reperfusion and, hence, neuroprotection. To test this hypothesis, we have developed an in vivo model to differentially monitor parenchymal and vascular reactive oxygen species (ROS) formation. By comparing the ROS-suppressing effect of N-tert-butyl-α-phenylnitrone (PBN) with its blood-brain barrier impermeable analog 2-sulfo-phenyl-N-tert-butylnitrone (S-PBN), we assessed the impact of vascular ROS suppression alone on reperfusion and stroke outcome after recanalization., Methods: The distal middle cerebral artery was occluded for 1 hour by compressing with a micropipette and then recanalized (n=60 Swiss mice). ROS formation was monitored for 1 hour after recanalization by intravital fluorescence microscopy in pial vasculature and cortical parenchyma with topically applied hydroethidine through a cranial window. PBN (100 mg/kg) or S-PBN (156 mg/kg) was administered shortly before recanalization, and suppression of the vascular and parenchymal hydroethidine fluorescence was examined (n=22). Microcirculatory patency, reperfusion, ischemic tissue size, and neurological outcome were also assessed in a separate group of mice 1 to 72 hours after recanalization (n=30)., Results: PBN and S-PBN completely suppressed the reperfusion-induced increase in ROS signal within vasculature. PBN readily suppressed ROS produced in parenchyma by 88%. S-PBN also suppressed the parenchymal ROS by 64% but starting 40 minutes later. Intriguingly, PBN and S-PBN comparably reduced the size of ischemic area by 65% and 48% ( P >0.05), respectively. S-PBN restored the microvascular patency and perfusion after recanalization, suggesting that its delayed parenchymal antioxidant effect could be secondary to improved microcirculatory reperfusion., Conclusions: Promoting microvascular reperfusion by protecting vasculature can secondarily reduce parenchymal ROS formation and provide neuroprotection. The model presented can be used to directly assess pharmacological end points postulated in brain parenchyma and vasculature in vivo., (© 2018 American Heart Association, Inc.)

Laparoscopic splenectomy became the gold standard recently for the removal of spleen. One of its rare indication is wandering spleen (WS). WS is characterized by incomplete fixation of the spleen. Patients usually have an asymptomatic abdominal mass. When they are symptomatic, abdominal pain with a mobile mass is the major finding. Laboratory data are nonspecific, but the diagnosis can be confirmed by imaging studies; computed tomography, magnetic resonance imaging, and ultrasonography are preferred modalities. It can predispose one to life-threatening complications such as splenic infarction, portal hypertension, pancretitis, and hemorrhage, due to torsion of its vascular pedicle. Herein, we present a female patient, a 24-year-old, 18-week primigravida. She was admitted with an intra-abdominal mass and lower abdominal pain. Ultrasonography revealed a mass behind the uterus. Magnetic resonance imaging was planned, and the spleen was seen at this area. We performed laparoscopic splenectomy for the treatment of a WS, which would be dangerous for pregnancy. The patient was discharged without any postoperative complication on the third day postoperatively. A healthy baby was delivered at term. Minimally invasive procedures should also be the primary choice in the treatment of such pregnant women. This is the first case of laparoscopic splenectomy in a pregnant woman for WS in the English literature.

Background and Purpose: Both necrotic and apoptotic cell death mechanisms are activated after cerebral ischemia. However, whether they are concomitantly active in the same cell or in discrete cell populations is not known., Methods: We investigated activation of both pathways at the cellular level in mice brains subjected to transient or permanent focal ischemia., Results: Four hours after ischemia, diffuse cathepsin-B spillage into cytoplasm, suggesting lysosomal leakage, was observed within neurons immunoreactive for the active form of caspase-3 (p20). Ischemic neurons with a leaky plasma membrane (positive for propidium iodide) were colabeled with caspase-cleaved actin fragment and exhibited TUNEL-positive nuclei having apoptotic morphology. At 72 hours, up to 27% of cells with caspase activity displayed morphological features suggestive of secondary necrosis., Conclusions: These data, demonstrating an early and concurrent increase in caspase-3 and cathepsin-B activities followed by appearance of caspase-cleavage products, DNA fragmentation, and membrane disintegration, suggest that subroutines of necrotic and apoptotic cell death are concomitantly activated in ischemic neurons and that the dominant cell death phenotype is determined by the relative speed of each process.

Background and Purpose: Use of thrombolysis in stroke is limited by a short therapeutic window because delayed reperfusion may cause brain hemorrhage and edema. Available evidence suggests a role for superoxide, NO, and peroxynitrite in reperfusion-induced injury. However, depending on their cellular origin and interactions between them, these molecules may exert protective or deleterious actions, neither of which is characterized in the intact brain., Methods: Using fluorescent probes, we determined superoxide and peroxynitrite formation within neurons, astrocytes, and endothelium, and the association between oxidative/nitrative stress and vascular injury in mice brains subjected to 2-hour middle cerebral artery occlusion and 3 or 5 hours of reperfusion., Results: Both signals were colocalized, suggesting that the main source of peroxynitrite in the reperfused brain was a reaction between superoxide and NO. Superoxide and peroxynitrite formation was particularly intense in microvessels and astrocytic end-feet surrounding them, and overlapped with dense mitochondrial labeling. Sites of oxidative/nitrative stress on microvessels were colocalized with markers of vascular injury such as Evans blue (EB) leakage and matrix metalloproteinase-9 (MMP-9) expression, suggesting an association between peroxynitrite and microvascular injury. Supporting this idea, partial inhibition of endothelial NO synthesis at reperfusion with a low dose of L-nitroarginine (1 mg/kg IP) reduced 3-nitrotyrosine formation in microvessels and EB extravasation., Conclusions: During reperfusion, intense superoxide, NO, and peroxynitrite formation on microvessels and surrounding end-feet may lead to cerebral hemorrhage and edema by disrupting microvascular integrity. Combination of thrombolysis with agents diminishing oxidative/nitrative stress may reduce reperfusion-induced injury and extend the therapeutic window for thrombolysis.

Background and Purpose: Synaptic transmission is highly vulnerable to metabolic perturbations. However, the long-term consequences of transient metabolic perturbations on synapses are not clear. We studied the long-lasting changes in synaptic transmission and phosphorylation of presynaptic proteins in penumbral cortical neurons after transient moderate ischemia., Methods: Rats were subjected to 1 hour of middle cerebral artery occlusion. After reperfusion, electric activity of neurons in the peri-infarct region was recorded intracellularly and extracellularly in situ. Phosphorylation of synapsin-I and tyrosine residues was studied by immunohistochemistry., Results: Neurons in the penumbra displayed no postsynaptic potentials 1 to 3 hours after recirculation. However, these cells were able to generate action potentials and were responsive to glutamate, suggesting that postsynaptic excitability was preserved but the synaptic transmission was blocked because of a presynaptic defect. The synaptic transmission was still depressed 24 hours after recirculation in neurons in the peri-infarct area that survived ischemia. The amount of immunoreactive synapsin-I, synaptophysin, and synaptotagmin was not appreciably changed for 72 hours after reperfusion. However, phosphorylation of synapsin-l was significantly decreased, whereas phosphotyrosine immunoreactivity was increased, suggesting a selective defect in synapsin-I phosphorylation., Conclusions: These data demonstrate that synaptic transmission may be permanently impaired after transient moderate brain injury. Since postsynaptic excitability is preserved, the transmission failure is likely to be caused by presynaptic mechanisms, one of which may be impaired phosphorylation of presynaptic proteins.