Artemis deficiency: A large cohort including a novel variant with increased radiosensitivity.

BACKGROUND: Artemis deficiency is an autosomal recessive disorder characterized by a combined immunodeficiency with increased cellular radiosensitivity. In this review, the clinical and genetic characteristics of 15 patients with DCLRE1C variants are presented. METHODS: The demographic, clinical, immunologic, and genetic characteristics of patients with confirmed DCLRE1C variants diagnosed between 2013 and 2023 were collected retrospectively. Three patients were evaluated for radiosensitivity by the Comet assay, compared with age- and sex-matched healthy control. RESULTS: Seven patients who had severe infections in the first 6 months of life were diagnosed with T-B-NK+ SCID (severe combined immunodeficiency). Among them, four individuals underwent transplantation, and one of those died due to post-transplant complications in early life. Eight patients had hypomorphic variants. Half of them were awaiting a suitable donor, while the other half had already undergone transplantation. The majority of patients were born into a consanguineous family (93.3%). Most patients had recurrent sinopulmonary infections (73.3%), and one patient had no other infection than an acute respiratory infection before diagnosis. Two patients (13.3%) had autoimmunity in the form of autoimmune hemolytic anemia. Growth retardation was observed in only one patient (6.6%), and no malignancy was detected in the surviving 11 patients during the median (IQR) of 21.5 (12-45) months of follow-up. Three patients who had novel variants exhibited increased radiosensitivity and compromised DNA repair, providing a potential vulnerability to malignant transformation. CONCLUSION: Early diagnosis, radiation avoidance, and careful preparation for transplantation contribute to minimizing complications, enhancing life expectancy, and improving the patient's quality of life.

Neurologic Status of Patients with Purine Nucleoside Phosphorylase Deficiency Before and After Hematopoetic Stem Cell Transplantation.

BACKGROUND: Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive combined immunodeficiency. The phenotype is profound T cell deficiency with variable B and NK cell functions and results in recurrent and persistent infections that typically begin in the first year of life. Neurologic findings occur in approximately two-thirds of patients. The mechanism of neurologic abnormalities is unclear. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for PNP deficiency. METHODS: We report here six patients from five unrelated families with PNP deficiency treated in two centers in Turkey. We evaluated the neurological status of patients and compared to post-transplantation period if available. Then, we performed PubMed, Google Scholar, and Researchgate searches using the terms "PNP" and "hematopoietic stem cell transplantation" to find all reported cases of PNP transplantation and compared to our cohort. RESULTS: Six patients were treated in two centers in Turkey. One patient died from post-transplant complications. The other four patients underwent successful HSCT with good immune reconstitution after transplantation (follow-up 21-48 months) and good neurological outcomes. The other patient with a new mutation is still waiting for a matching HLA donor. DISCUSSION: In PNP deficiency, clinical manifestations are variable, and this disease should be considered in the presence of many different clinical findings. Despite the comorbidities that occurred before transplantation, HSCT currently appears to be the only treatment option for this disease. HSCT not only cures immunologic disorders, but probably also improves or at least stabilizes the neurologic status of patients.

Effects of Ozone on Injury after Gamma Knife Radiosurgery.

BACKGROUND: At present, gamma knife radiosurgery plays an important role in neurosurgical procedures. Gamma knife radiosurgery has been used to treat many types of brain tumors and as a functional intervention. However, gamma knife treatment has a devastating effect on the normal brain parenchyma surrounding the target point. It causes increased vascular permeability, vasodilation, and swelling in endothelial cells. Ozone has antioxidant, antiapoptotic, and anti-inflammatory effects in the body. Thus, we evaluated the radioprotective effects of ozone in rats undergoing gamma knife radiation. METHODS: In the present study, 24 Sprague-Dawley male rats weighing 250-300 g in 3 groups of 8 rats each were used. The rats were selected randomly. The control group did not receive any gamma knife radiation. The other 2 groups received 50 Gy of radiation, with 1 group given ozone treatment and the other group not given ozone treatment after gamma knife radiosurgery. At 12 weeks after gamma knife radiation, the rats were sacrificed with high-dose anesthetic agents and the tissues prepared for evaluation. The slides were evaluated for necrosis, vacuolization, glial proliferation, and vascular proliferation using hematoxylin-eosin staining. Vascular endothelial growth factor (VEGF) and extracellular matrix metalloproteinase inducer (also known as CD147) were evaluated using immunohistochemical staining. RESULTS: VEGF expression in glial tissue was significantly less in the group receiving ozone (χ2 = 15.00; df = 4; P = 0.005) compared with the group that had not received ozone and was similar to the expression in the control group. CONCLUSIONS: The lower expression of VEGF in the group receiving ozone might cause less edema in the surrounding tissue owing to less degradation of vascular permeability in the rat brain tissue.

The Histological Effects of Ozone Therapy on Sciatic Nerve Crush Injury in Rats.

OBJECTIVE: Peripheral nerve injury is a common, important problem that lacks a definitive, effective treatment. It can cause neurologic deficits ranging from paresthesia to paralysis. This study evaluated the effect of ozone therapy on sciatic nerve crush injury in rats. MATERIALS AND METHODS: Twenty-four male rats were divided into control sham surgery, sciatic nerve injury, and sciatic nerve injury with ozone groups (each n = 8). The sciatic nerve injury was inflicted via De Koning's crush-force method. The sciatic nerve injury group received medical air and the sciatic nerve injury ozone group received 0.7 mg/kg ozone. Sciatic nerve samples were obtained 4 weeks after injury. Vascular congestion, vacuolization, edema formation, S100 expression, and the thicknesses of the perineurium and endoneurium and diameter of the injured sciatic nerves were evaluated. RESULTS: The diameter of the sciatic nerve and thicknesses of the perineurium and epineurium were significantly greater in the sciatic nerve injury group (P < 0.05) and significantly less in the sciatic nerve injury with ozone group (P < 0.001). High S100 immunoreactivity was seen in the sciatic nerve injury group compared with the other 2 groups (P < 0.05). The distributions of vascular congestion and vacuolization were significantly less in the sciatic nerve injury with ozone group (P < 0.05). CONCLUSIONS: Ozone therapy improved sciatic nerve injury recovery without causing an increase in fibrotic tissue. Ozone reduced fibrosis, vascular congestion, vacuolization, and edema in rodents. Ozone treatment might be used to assist in sciatic nerve injury.

The Effect of Ozone Therapy on Experimental Vasospasm in the Rat Femoral Artery.

AIM: Oxidation products following subarachnoid hemorrhage (SAH) are among the causative substances of cerebral vasospasm and poor outcome. Ozone (O3) is a gas that contains three atoms of oxygen with a cyclic structure. It has been suggested that application of low-dose ozone has an antioxidant effect and provides resistance to oxidative stress. We investigated the effect of oxygen-ozone therapy on rat femoral artery vasospasm. MATERIAL AND METHODS: Twenty-four male Sprague-Dawley rats were randomly separated into vasospasm, vasospasm + ozone and control groups. The femoral artery vasospasm model was used. Rats in the vasospasm + ozone group were given 4 mL of ozone (20 µ/mL) daily for 7 days. Femoral arteries were examined by light microscopy for histological changes and morphometric analysis. Kruskal Wallis test and Mann Whitney U tests were used for the statistical analysis. The values of p < 0.01 and p < 0.05 were recognized as statistically significant. RESULTS: Ozone treatment reduced the morphometric changes as irregularity of the elastic lamina, disruption of the endothelial cells, vacuolization and hemorrhages that caused by vasospasm. The measurements of the wall thickness (p=0.003; p < 0.01) and lumen diameter (p=0.001; p < 0.01) showed statistically significant difference (p < 0.01) between the vasospasm and vasospasm+ozone groups. CONCLUSION: Ozone therapy may be useful in the treatment of post-hemorrhagic vasospasm.

Tunable conduction type of solution-processed germanium nanoparticle based field effect transistors and their inverter integration.

In this work we demonstrate the fabrication of germanium nanoparticle (NP) based electronics. The whole process chain from the nanoparticle production up to the point of inverter integration is covered. Ge NPs with a mean diameter of 33 nm and a geometric standard deviation of 1.19 are synthesized in the gas phase by thermal decomposition of GeH4 precursor in a seeded growth process. Dispersions of these particles in ethanol are employed to fabricate thin particulate films (60 to 120 nm in thickness) on substrates with a pre-patterned interdigitated aluminum electrode structure. The effect of temperature treatment, polymethyl methacrylate encapsulation and alumina coating by plasma-assisted atomic layer deposition (employing various temperatures) on the performance of these layers as thin film transistors (TFTs) is investigated. This coating combined with thermal annealing delivers ambipolar TFTs which show an Ion/Ioff ratio in the range of 10(2). We report fabrication of n-type, p-type or ambipolar Ge NP TFTs at maximum temperatures of 450 °C. For the first time, a circuit using two ambipolar TFTs is demonstrated to function as a NOT gate with an inverter gain of up to 4 which can be operated at room temperature in ambient air.