Search

Mitochondrial respiratory chain dysfunction and impaired oxidative phosphorylation are rare but significant causes of mitochondrial diseases in children, presenting with diverse clinical features. Combined oxidative phosphorylation deficiency type 23 (COXPD23), an autosomal recessive disorder due to GTPBP3 gene mutations, typically manifests as lactic acidosis, hypertrophic cardiomyopathy, and encephalopathy. This case report describes a male infant born at 35 weeks gestation, who exhibited severe lactic aciduria and hypotonia but no cardiomyopathy, which is atypical for COXPD23. Genetic analysis revealed a novel homozygous missense variant in the GTPBP3 gene. Despite intensive metabolic and supportive treatments, the patient's condition worsened, leading to death on the 23rd day. This case emphasizes the need to consider mitochondrial cytopathies in neonates with persistent metabolic acidosis and hyperlactatemia and highlights the importance of early genetic screening for accurate diagnosis and management., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease, with a high mortality if left untreated. In addition, the disease has unique diagnostic challenges. Therefore, despite the existing guidelines on management, current clinical practice data is informative on the course and outcome. Herein, a retrospective chart review study was conducted through the collaboration of six centers, located in central and southeastern Türkiye. The demographical data, laboratory results, and treatment outcomes were evaluated. Eighty-three patients were enrolled in the study. The mean age was 2 years, whereas the median age was 8 months with a range of a minimum of 1 week and a maximum of 12.6 years. Consanguineous marriage, history of sibling death, and familial history of similar disease were determined in 72.2% (n:60), 34.9% (n:29), and 39.8% (n:33) of the patients, respectively. The most common presentation was fever, followed by hepatosplenomegaly on admission. Disease-causing familial HLH variants were identified in 60.2% (n:50) of the patients. Hematopoietic stem cell transplantation (HSCT) was performed in 39.7% (n:33) of the cohort. The 2-year overall survival (OS) rate was 62.4% for the whole group. Comparing the patients who received HSCT and those who did not; the HSCT group had a 2-year OS of 84.7%, which was significantly better than patients who did not receive HSCT had a 2-year OS of 47.1% (p:0.001). Despite the improvement in HLH diagnostics and treatment options over the last decade, early death remains a leading problem for the survival of these patients. Therefore, appropriate assessment of the patients in experienced centers and HSCT are pivotal for better outcomes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Erciyes University Faculty of Medicine on 07.12.2022 and the approval number is 2022/795. Consent to participate: All participants provided informed consent in the format required by the relevant authorities and/or boards for publication of their data in Tables 1 and 2., (© 2024. The Author(s).)

Some clinical signs such as cachexia, alopecia, exfoliative dermatitis, hair loss, and swollen lymph nodes were observed in a one-year-old crossbred male dog living in a rural area of Kirikkale province, Türkiye, was presented to the veterinary clinic by its owner. Anaemia, leucopenia, hyperglobulinemia, and bilirubinemia were detected. Seropositivity was detected using Leishmania IgG/IgM Rapid Test. The amastigote forms of the parasite were observed in the lymph node aspirates. Viable promastigotes were observed in the samples obtained from the Novy-MacNeal-Nicolle medium (NNN) tubes. The parasite DNA was extracted from the promastigotes produced in the NNN medium using a DNA extraction kit according to the manufacturer's instructions. The specific bands indicating the gene regions of L. infantum (350 bp and 730 bp for HSP20 and HSP70, respectively) were observed. Additionally, BLASTn analysis revealed 100 % similarity with GenBank-deposited L. infantum sequences. The sequences were submitted to GenBank (Accession numbers: OR806945 and OR806946). According to the author's knowledge, it is the first dog isolate deposited in the collection of the Microbiology Reference Laboratories and Biological Products Department, General Directorate of Public Health, Ministry of Health, Ankara, Türkiye. The isolate (TR_L. infantum CanL-1_damla) has been preserved by cryopreservation at -150 °C for further studies., Competing Interests: Declaration of competing interest No conflict of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

This study aimed to report the presence of Mesocestoides litteratus in dogs adopted from shelters in Türkiye. Gravid segments were examined microscopically in the faeces of dogs from different shelters located in Ankara and Kirikkale provinces in the central region of Türkiye. Then, genomic DNA obtained from these segments, a 446-bp fragment of the mitochondrial cytochrome C oxidase subunit 1 gene, and a 350-bp fragment of mitochondrial 12S rRNA were amplified and sequenced. BLASTn search was performed. During light microscopic examination, an egg-filled paruterine organ was observed in the middle part of the segment. Thin-shelled, oval, 35-µm-diameter parasite eggs containing an oncosphere with three pairs of hooklets were observed. The gravid segments were determined as Mesocestoides spp. based on the appearance of the typical paruterine organ. PCR results supported our diagnosis; moreover, according to the BLAST results, it was detected that the species infecting two dogs was 98.01-100% similar to M. litteratus. Praziquantel-containing medication was administered to the infected dogs at a dosage of 5 mg/kg. Foxes act as the final host of M. litteratus and the parasite is prevalent in wildlife; however, these animals may disperse the parasite in urban life. Veterinarians need to be made more aware of this parasite, especially if the dogs are owned from shelters., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

BACKGROUND Neonatal hypoxic-ischemic encephalopathy (HIE) is a significant cause of perinatal and postnatal morbidity and mortality worldwide. Catalase (CAT) activity detection is used to determine levels of inflammation and oxidative stress. Glutathione (GSH) is the most critical non-enzymatic endogenous antioxidant. Lipid peroxidation levels marked after hypoxia can be detected based on the level of malondialdehyde (MDA). Ischemia-modified albumin (IMA) is considered a biomarker for cardiac ischemia and is known to increase in the liver, brain, and kidney in states of insufficient oxygenation. We aimed to explain the results and relations between the oxidant and antioxidants to detail oxidant-antioxidant balance and cellular mechanisms. MATERIAL AND METHODS Serum levels of IMA and MDA, as an oxidative stress marker, and CAT and GSH, as antioxidant enzymes, were measured in first blood samples of 59 neonates diagnosed with HIE, with pH <7, base excess >12, and APGAR scores. RESULTS Neonates who were ≥37 weeks of gestation and had hypoxia were included. Compared with healthy newborns (n=32), CAT was statistically significantly lower in the hypoxia group (P=0.0001), while MDA serum levels were significantly higher in neonates with hypoxia (P=0.01). There was no difference between hypoxic and healthy neonates in GSH and IMA measurements (P=0.054, P=0.19 respectively). CONCLUSIONS HIE pathophysiology involves oxidative stress and mitochondrial energy production failure. Explaining the pathways between oxidant-antioxidant balance and cell death, which explains the pathophysiology of HIE, is essential to develop treatment strategies that will minimize the effects of oxygen deprivation on other body organs, especially the brain.

Background: Neonatal hypoxia ischemia (HI) related brain injury is one of the major causes of life-long neurological morbidities that result in learning and memory impairments. Evidence suggests that male neonates are more susceptible to the detrimental effects of HI, yet the mechanisms mediating these sex-specific responses to neural injury in neonates remain poorly understood. We previously tested the effects of treatment with a small molecule agonist of the tyrosine kinase B receptor (TrkB), 7,8-dihydroxyflavone (DHF) following neonatal HI and determined that females, but not males exhibit increased phosphorylation of TrkB and reduced apoptosis in their hippocampi. Moreover, these female-specific effects of the TrkB agonist were found to be dependent upon the expression of Erα. These findings demonstrated that TrkB activation in the presence of Erα comprises one pathway by which neuroprotection may be conferred in a female-specific manner. The goal of this study was to determine the role of Erα-dependent TrkB-mediated neuroprotection in memory and anxiety in young adult mice exposed to HI during the neonatal period., Methods: In this study, we used a unilateral hypoxic ischemic (HI) mouse model. Erα +/+ or Erα -/- mice were subjected to HI on postnatal day (P) 9 and mice were treated with either vehicle control or the TrkB agonist, DHF, for 7 days following HI. When mice reached young adulthood, we used the novel object recognition, novel object location and open field tests to assess long-term memory and anxiety-like behavior. The brains were then assessed for tissue damage using immunohistochemistry., Results: Neonatal DHF treatment prevented HI-induced decrements in recognition and location memory in adulthood in females, but not in males. This protective effect was absent in female mice lacking Erα. The female-specific improved recognition and location memory outcomes in adulthood conferred by DHF therapy after neonatal HI tended to be or were Erα-dependent, respectively. Interestingly, DHF triggered anxiety-like behavior in both sexes only in the mice that lacked Erα. When we assessed the severity of injury, we found that DHF therapy did not decrease the percent tissue loss in proportion to functional recovery. We additionally observed that the presence of Erα significantly reduced overall HI-associated mortality in both sexes., Conclusions: These observations provide evidence for a therapeutic role for DHF in which TrkB-mediated sustained recovery of recognition and location memories in females are Erα-associated and dependent, respectively. However, the beneficial effects of DHF therapy did not include reduction of gross tissue loss but may be derived from the enhanced functioning of residual tissues in a cell-specific manner., (© 2024. The Author(s).)

Background: Spontaneous subarachnoid hemorrhage (SAH) is the most severe form of hemorrhagic stroke and accounts for 5-7% of all strokes. Several chemical enzymes and cytokines are thought to cause reactions that may affect the mortality and morbidity of SAH patients. This study aimed to examine the possible relationships between these parameters and the occurrence of SAH and the clinical-radiological parameters in patients with acute SAH., Methods: This study evaluated 44 patients, including 20 with SAH and 24 controls. We obtained blood from the patients and control groups, which was stored in heparinized tubes and used in determining tumor necrosis factor alpha (TNF-α), brain-derived neurotrophic factor (BDNF), acetylcholinesterase (AChE), caspase-3, and butyrylcholinesterase (BChE) enzymes., Results: TNF-α, BDNF, AChE, and BChE enzyme levels were not related to the Glasgow Coma scale (GCS) score in the patient group ( p > 0.05), whereas higher enzyme levels of caspase-3 were associated with lower GCS scores ( p < 0.05). The difference between the control and patient groups in terms of mean TNF-α levels was statistically significant ( p < 0.01). The BDNF levels were statistically insignificant in the patient groups ( p > 0.05). Caspase-3, AChE, and BChE levels were significantly different between the control and patient groups ( p < 0.01)., Conclusions: Our results may be valuable for predicting the prognosis, diagnosis, and follow-up of patients with SAH. However, further studies are required to elucidate the relationship between the clinical and radiological results in patients with SAH and certain enzymes, cytokines, and growth factors., Competing Interests: Conflict of interest: The authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter.)

Background: Neonatal hypoxia ischemia (HI) related brain injury is one of the major causes of life-long neurological morbidities that result in learning and memory impairments. Evidence suggests that male neonates are more susceptible to the detrimental effects of HI, yet the mechanisms mediating these sex-specific responses to neural injury in neonates remain poorly understood. We previously tested the effects of treatment with a small molecule agonist of the tyrosine kinase B receptor (TrkB), 7,8-dihydroxyflavone (DHF) following neonatal HI and determined that females, but not males exhibit increased phosphorylation of TrkB and reduced apoptosis in their hippocampi. Moreover, these female-specific effects of the TrkB agonist were found to be dependent upon the expression of ERα. These findings demonstrated that TrkB activation in the presence of ERα comprises one pathway by which neuroprotection may be conferred in a female-specific manner. The goal of this study was to determine the role of ERα-dependent TrkB-mediated neuroprotection in memory and anxiety in young adult mice exposed to HI during the neonatal period., Methods: In this study we used a unilateral hypoxic ischemic (HI) mouse model. ERα +/+ or ERα -/- mice were subjected to HI on postnatal day (P) 9 and mice were treated with either vehicle control or the TrkB agonist, DHF, for seven days following HI. When mice reached young adulthood, we used the novel object recognition, novel object location and open field tests to assess long-term memory and anxiety like behavior. The brains were then assessed for tissue damage using immunohistochemistry., Results: Neonatal DHF treatment prevented HI-induced decrements in recognition and location memory in adulthood in females, but not in males. This protective effect was absent in female mice lacking ERα. Thus, the female-specific and ERα-dependent neuroprotection conferred by DHF therapy after neonatal HI was associated with improved learning and memory outcomes in adulthood. Interestingly, DHF triggered anxiety like behavior in both sexes only in the mice that lacked ERα. When we assessed the severity of injury, we found that DHF therapy did not decrease the percent tissue loss in proportion to functional recovery. We additionally observed that the presence of ERα significantly reduced overall HI-associated mortality in both sexes., Conclusions: These observations provide evidence for a therapeutic role for DHF in which sustained recovery of memory in females is TrkB-mediated and ERα-dependent. However, the beneficial effects of DHF therapy did not include reduction of gross tissue loss but may be derived from the enhanced functioning of residual tissues in a cell-specific manner., Competing Interests: Competing interests This work was supported by R01NS111021 to Pelin Cengiz. Jon E. Levine is supported by R01DK121559-01, R21HD102172-01, and U24MH123422-01. Karyn M. Frick is supported by R01MH107886, Alzheimer’s Association ABA-22-973796, and multiple grants from the UWM Research Foundation and UWM Graduate School. Dr. Frick is a co-founder and the Chief Scientific Officer of Estrigenix Therapeutics, Inc., a company which aims to improve women’s health by developing safe, clinically proven treatments for the mental and physical effects of menopause. The rest of the authors do not have any conflicts of interests to declare.

Objective: Spinal metastases may only affect the bone tissue and result in spinal instability or may additionally result in epidural compression, leading to neurological deficits. Surgery has emerged as a popular method in treating metastatic epidural spinal cord compression (MESCC) due to the advances in surgical techniques and instrumentation. In this study, we evaluated patients with MESCC regarding neurological status, pain status, and survival rates, and presented our experience managing MESCC., Patients and Methods: Clinical and radiographic records of 53 patients diagnosed with MESCC between January 2011 and March 2017 were retrospectively evaluated. The study included patients with a pathological diagnosis of primary cancer, those who complained of spinal metastasis, and those who had indications of MESCC on Magnetic Resonance Imaging (MRI). Bone structure and spinal stability were evaluated using assessed Computed Tomography (CT), and metastatic spread was considered using assessed Positron Emission Tomography (PET) in suitable cases. For each patient, the presence of a tumor compressing the spinal cord, age, gender, preoperative, and postoperative American Spinal Injury Association scores (ASIA), Tokuhashi prognostic score (TPS), affected spinal segment, pathological diagnosis, preoperative, and postoperative Visual Analog Scale (VAS), the status of spinal stability, follow-up period, and complications were evaluated., Results: Forty-five patients (82.2% of them were women) underwent surgery with a mean age of 58.29 ± 15.14 years. The most frequent type of primary tumor was multiple myeloma (33.9%), followed by lung (24.6%), gastric (7.5%), and prostate (5.7%). The most common site of metastasis was the thoracic region (43.4%), followed by lumbar (24.5%), multiple (24.5%), and cervical (5.7%). The analysis indicated that a significant difference was found between the survival rates of the TPS categories., Conclusions: Common symptoms of MESCC include spinal pain and neurological deficit below the level of the injury. Prompt surgical treatment followed by oncological treatment leads to significant neurological recovery, more prolonged survival, pain relief, and improved quality of life in patients with a short survival time. Oncological treatments, including radiotherapy (RT), should be recommended after surgical treatment.

The intricate system of connections between the eye and the brain implies that there are common pathways for the eye and brain that get activated following injury. Hypoxia-ischemia (HI) related encephalopathy is a consequence of brain injury caused by oxygen and blood flow deprivation that may result in visual disturbances and neurodevelopmental disorders in surviving neonates. We have previously shown that the tyrosine receptor kinase B (TrkB) agonist/modulator improves neuronal survival and long-term neuroprotection in a sexually differential way. In this study, we tested the hypotheses that; 1) TrkB agonist therapy improves the visual function in a sexually differential way; 2) Visual function detected by electroretinogram (ERG) correlates with severity of brain injury detected by magnetic resonance (MRI) imaging following neonatal HI in mice. To test our hypotheses, we used C57/BL6 mice at postnatal day (P) 9 and subjected them to either Vannucci's rodent model of neonatal HI or sham surgery. ERG was performed at P 30, 60, and 90. MRI was performed following the completion of the ERG. ERG in these mice showed that the a-wave is normal, but the b-wave amplitude is severely abnormal, reducing the b/a wave amplitude ratio. Inner retina function was found to be perturbed as we detected severely attenuated oscillatory potential after HI. No sex differences were detected in the injury and severity pattern to the retina as well as in response to 7,8-DHF therapy. Strong correlations were detected between the percent change in b/a ratio and percent hemispheric/hippocampal tissue loss obtained by MRI, suggesting that ERG is a valuable noninvasive tool that can predict the long-term severity of brain injury., Competing Interests: Declaration of competing interest Pelin Cengiz has Grant from NIH/NINDS R01 NS111021, NIH/NINDS K08 NS088563, and NIH Waisman Core Grant P50HD105353. Bikash R. Pattnaik has Grants from McPherson Eye Research Institute RRF MD Matthews Research Professorship and National Institute of Health (R01EY024995)., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Neonatal encephalopathy due to hypoxia-ischemia (HI) leads to severe, life-long morbidities in thousands of neonates born in the USA and worldwide each year. Varying capacities of long-term episodic memory, verbal working memory, and learning can present without cerebral palsy and have been associated with the severity of neonatal encephalopathy sustained at birth. Among children who sustain a moderate degree of HI at birth, girls have larger hippocampal volumes compared to boys. Clinical studies indicate that female neonatal brains are more resistant to the effects of neonatal HI, resulting in better long-term cognitive outcomes compared to males with comparable brain injury. Our most recent mechanistic studies have addressed the origins and cellular basis of sex differences in hippocampal neuroprotection following neonatal HI-related brain injury and implicate estrogen receptor-α (ERα) in the neurotrophin receptor-mediated hippocampal neuroprotection in female mice. This review summarizes the recent findings on ERα-dependent, neurotrophin-mediated hippocampal neuroprotection and weighs the evidence that this mechanism plays an important role in preservation of long-term memory and learning following HI in females., (© 2019 S. Karger AG, Basel.)

Spinal epidural abscess (SEA) is a rare disease which is often rapidly progressive. Delayed diagnosis of SEA may lead to serious complications and the clinical findings of SEA are generally nonspecific. Paraspinal abscess should be considered in the presence of local low back tenderness, redness, and pain with fever, particularly in children. In case of delayed diagnosis and treatment, SEA may spread to the epidural space and may cause neurological deficits. Magnetic resonance imaging (MRI) remains the method of choice in the diagnosis of SEA. Treatment of SEA often consists of both medical and surgical therapy including drainage with percutaneous entry, corpectomy, and instrumentation.

Background: On October 23, 2011, a devastating earthquake, magnitude 7.2 on the Richter Scale, jolted the province of Van in the east of Turkey and led to hundreds of casualties., Objectives: In this study, we aimed to present our clinical experience in the management of patients with cranial and spinal injuries who were admitted to the Van Regional Training and Research Hospital., Methods: The retrospective study included 44 (77.2%) patients who were referred to the neurosurgery department after being diagnosed with spinal and cranial injuries due to earthquake at the emergency department between October 23 and 27, 2011., Results: The patients comprised 32 male (72.7%) and 12 (27.3%) female patients with a mean age of 23.5 years. The injuries included scalp injury (n = 16), burst fracture (n=7), compression fracture (n=3), epidural hematoma (n=9), subdural hematoma (n=3), contusion (n=1), traumatic subarachnoid hemorrhage (n=2), depressed skull fracture (n=3), linear fracture (n=9), cervical fracture (n=2), and pneumocephalus (n=1). Most of the patients (90.9%) had isolated injuries and the others (9.1%) presented with combined cranial and spinal injuries. At discharge, the 3 patients with spinal fractures were paraplegic, and of the 2 patients who were operatively treated due to subdural hematoma, 1 was hemiparesic and the other was hemiplegic. No mortality occurred in our patients., Conclusions: The results of this study demonstrated that, in the aftermath of a natural disaster, conducting correct triage procedures and performing a prompt intervention with appropriate and qualified equipment play key roles in reducing morbidity and mortality., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: To determine the possible impact of recurrent wheeze on immunisation status in the first three years of life., Method: A cross-sectional case control study of 288 children less than three years of age with a history of recurrent wheezing, hospitalised at a single centre for wheeze; and a control group of 190 children with no prior history of wheezing. Vaccination charts of all children were analysed according to the National Immunisation Schedule. Additionally, some associated data were collected through a questionnaire to the parents., Results: Children with recurrent wheezing during the first three years of life were less likely to be vaccinated against BCG (Bacillus-Calmette-Guerin), hepatitis B, Hib (Haemophilus influenza type B), and MMR (Measles, Mumps, Rubella) (p < 0.001). A significant inverse association was also found between the number of wheezy episodes and the number of vaccine doses received. The odds ratio of incomplete vaccination in children with recurrent wheeze was 10.6 (95% CI, 2.96 to 38.1)., Conclusion: Children under three years of age with recurrent wheeze run a high risk of incomplete immunisation. Efforts should be therefore made to insure that such children receive adequate vaccination., (Copyright © 2010 SEICAP. Published by Elsevier Espana. All rights reserved.)

The mother's mental state as a risk factor for the children's vaccination status in developing countries has received little attention. The aim of this study was to determine the association between childhood vaccination coverage and maternal anxiety. A total of 195 consecutive infants and their mothers attending a tertiary teaching hospital, department of pediatric outpatient center between January 2008 and September 2009 were included in the study. One hundred five infants who have incomplete vaccination schedule (according to the National Immunization Schedule) were matched with 90 controls (fully vaccinated) and their mothers self-report measure of anxiety level using the State-Trait Anxiety Inventory (STAI), a psychiatric screening instrument. The chi-square test and the logistic regression were used in the statistical analysis. High maternal anxiety levels determined by STAI was associated with increased risk of incomplete vaccination status in infants (odds ratio 4.35, 95% confidence interval 1.87-8.79).This association remained significant after controlling for sociodemographic factors. High maternal anxiety scores may result in incomplete vaccination status in children younger than 3 years.

The aim of this study was to determine seroprevalence of Neospora caninum in dairy cattle ranches with higher abortion rates and co-existence of Neospora caninum, Toxoplasma gondii, Brucella abortus, and Listeria monocytogenes antibodies. The blood samples were collected from dairy cows with history of abortion (n=234) as well as from pregnant cows that were (n=323) kept in the same ranches. N. caninum seroprevalence was 10.77% (60/557). The co-existence rate of N. caninum seropositivity with T. gondii, B. abortus and L. monocytogenes was 24.77% (138/557), 13.82% (77/557) and 42.85% (162/378), respectively. Only one animal had significant antibody titers for all analyzed infectious agents. The seroprevalence of N. caninum and T. gondii were significantly higher in pregnant cows than aborted cows (p<0.05 and p<0.001, respectively). As a result, the comprehensive data generated through this study can significantly contribute to understanding of serologic association of N. caninum with T. gondii, B. abortus and L. monocytogenes in pregnant and aborted dairy cows.

Heartworm infection is one of the most important parasitic diseases in dogs. The aim of the present study was to determine the prevalence of heartworm in dogs in Kirikkale. Blood samples of 172 dogs were collected. Microfilariae were detected in 10 (5.8%). dogs with the Knott technique. The anal and excretory pores stained with acid phosphates showed that the microfilariae belonged to Dirofilaria immitis. Microfilariae were found in dogs aged between 2-10 years, and especially in Siberian huskies, setters, pointers and crossbred sheepdogs. The serum samples of 142 dogs were analyzed using the commercial ELISA test kit for detection of anti-D. immitis antibody. The occult infection rate was found to be 27.46% in dogs. According to these results, Kirikkale region has a high risk for heartworm infection.