LETM1-Mediated K+ and Na+ Homeostasis Regulates Mitochondrial Ca2+ Efflux

HIGHLIGHTS \u2022 Monovalent cation homeostasis is dysregulated upon LETM1 depletion \u2022 K+/H+ exchange activity is decreased in LETM1 knockdown cells \u2022 LETM1 depletion results in K+ accumulation in the mitochondrial matrix \u2022 LETM1 knockdown does not affect expression of major mitochondrial Ca2+ transport modulators \u2022 LETM1-regulated mitochondrial Ca2+ fluxes are dependent on Na+ Ca2+ transport across the inner membrane of mitochondria (IMM) is of major importance for their functions in bioenergetics, cell death and signaling. It is therefore tightly regulated. It has been recently proposed that LETM1\u2014an IMM protein with a crucial role in mitochondrial K+/H+ exchange and volume homeostasis\u2014also acts as a Ca2+/H+ exchanger. Here we show for the first time that lowering LETM1 gene expression by shRNA hampers mitochondrial K+/H+ and Na+/H+ exchange. Decreased exchange activity resulted in matrix K+ accumulation in these mitochondria. Furthermore, LETM1 depletion selectively decreased Na+/Ca2+ exchange mediated by NCLX, as observed in the presence of ruthenium red, a blocker of the Mitochondrial Ca2+ Uniporter (MCU). These data confirm a key role of LETM1 in monovalent cation homeostasis, and suggest that the effects of its modulation on mitochondrial transmembrane Ca2+ fluxes may reflect those on Na+/H+ exchange activity

Effects of low level laser therapy on mucositis in patients under chemotherapy and bone marrow transplantation

Background: Oral mucositis is among the most important adverse effects of chemotherapy and bone marrow transplantation and prevention from this side effect is important to improve the situations in patients. Hence, in this study the main aim was to determine the effects of low-level laser therapy on mucositis in patients under chemotherapy and bone marrow transplantation. Materials and Methods: In this randomized controlled clinical trial, 60 consecutive patients under chemotherapy and bone marrow transplantation in a training hospital in 2018 were enrolled and randomly assigned to receive either low-level laser therapy (630 and 780 nm) or off-laser. Finally, the frequency rate and severity of mucositis (grades 0 to 4 according to WHO severity index) were determined and compared across the groups. Results: Mucositis was present in 30% and 56.7% in laser and control groups, respectively with statistically significant difference (p=0.037). The severity of mucositis was same across the laser and control groups (p=0.785). Conclusion: Low-level laser therapy is an effective modality for preventing from mucositis in patients treated by chemotherapy and bone marrow transplantation. Accordingly, utilization of this safe and effective therapeutic method is recommended

Plethysmography Variability Index as a Guidance for Intraoperative Fluid Management in Cesarean Section Delivery under Spinal Anesthesia: A Pilot Study

Background: Plethysmography variability index (PVI) is a measure of the dynamic changes in the perfusion index (PI) that occur during one or more complete respiratory cycles. This study was designed to investigate the accuracy of PVI in guidance of fluid management in parturient undergoing cesarean section surgery under spinal anesthesia.Methods: This randomized clinical trial was performed on 21 consecutive patients who were candidate for cesarean section surgery under spinal anesthesia at Shariati Hospital in Tehran, Iran, between April 2015 and April 2016. The patients were randomly assigned to one of the PVI or conventional group. In all patients, serum level of lactate, mean arterial pressure (MAP), total amount of infused intraoperative fluids, urine output, and duration of surgery were recorded.Results: In total, 21 patients (10 in PVI group and 11 in control group) were assessed. The trend of the change in MAP was significantly different between the two groups with a downward trend in PVI group and a fluctuated trend in the conventional group (P = 0.003). The mean amount of infused fluid was 2565.00 ± 563.74 ml in PVI group that was significantly lower than control group (3122.73 ± 321.99 ml) (P = 0.011). Although urine output was numerically higher in PVI than in control group (425.00 ± 274.12 ml vs. 322.00 ± 121.82 ml), it was not statistically significant (P = 0.292). In PVI group, the primary value of PVI was 23.80 ± 6.93 that reached to 12.20 ± 1.75 at the end of surgery indicating a significant reduction (P < 0.001).Conclusions: Regarding clinical and hemodynamic stability as well as fluid therapy responsiveness (less requiring fluids within surgery), PVI monitoring seems to be superior to the conventional method

Development and psychometric evaluation of the Persian version of the Phoneme Recognition Test A central auditory processing measure

  Objectives The present study evaluating the psychometric properties of the Persian version of the Phoneme Recognition Test (P-PRT) in normal subjects and cochlear implant (CI) users. Material & Methods This study includes developing the Persian phoneme recognition test (PRT), determining its validity and reliability, and comparing the results of a control group versus CI users. The test reliability was examined through a test-retest with an approximately five-week interval. In the present survey, 363 subjects were investigated in three stages. The face validity evaluation stage was conducted on 40 subjects. The psychometric properties of the P-PRT were evaluated in 323 individuals (225 normal subjects and 98 CI users). The test-retest reliability was examined in all the 225 subjects in the control groupand 40 CI users. ResultsThe results confirmed the face validity of the P-PRT. No significant differences were observed between the two genders in terms of performance in the P-PRT. Significant differences were observed between the control and CI groups. Evaluating the test-retest reliability suggested perfect reliability (r>0.9) in both groups. Significant differences were observed in the P-PRT between the adults and the 7-year-old subjects compared to other age groups. Conclusion The P-PRT can be used as a valid and reliable test for clinically evaluating phoneme recognition abilities and monitoring the rehabilitation progres

In Vitro Study of Leishmanicidal Activity of Biogenic Selenium Nanoparticles against Iranian Isolate of Sensitive and Glucantime- Resistant Leishmania tropica

Background: Sensitive and glucantime (MA) resistance Leishmania tropica are referred to those isolates, which are responsive, or non-responsive to one or two full courses of treatment by MA systematically and/or intra-lesionally, respectively. In this study, we evaluated the antileishmanial activity of biogenic selenium nanoparticles (Se NPs) alone and in combination with MA against sensitive and glucantimeresistant L. tropica on in vitro model. Methods: The Se NPs were synthesized by employing the Bacillus sp. MSh-1. The antileishmanial effects of Se NPs alone and in combination with MA on promastigote and amastigote stages of sensitive and glucantime-resistant L. tropica strains have been investigated using a colorimetric MTT assay and in a macrophage model. In addition hemolytic activity in type O+ human red blood cells and infectivity rate of the promastigotes before and after treatment with the Se NPs was evaluated. Results: In the promastigote stage, various concentrations of Se NPs significantly inhibited (P<0.05) the growth of promastigotes of both strains in a dose-dependent manner. Similarly, Se NPs especially in combination with MA significantly reduced the mean number of amastigotes of both strains in each macrophage. Se NPs showed no hemolytic effect on human RBCs at low concentrations. Moreover, infection rate of macrophages by promastigotes significantly (P<0.05) was reduced when promastigotes pre-treated with Se NPs. Conclusion: The findings of this study suggest a first step in the search of Se NPs as a new antileishmanial agent. Further experiments are needed to investigate antileishmanial effects of biogenic Se NPs on L. tropica using a clinical setting

High-bandwidth AFM-based rheology is a sensitive indicator of early cartilage aggrecan degradation relevant to mouse models of osteoarthritis

Murine models of osteoarthritis (OA) and post-traumatic OA have been widely used to study the development and progression of these diseases using genetically engineered mouse strains along with surgical or biochemical interventions. However, due to the small size and thickness of murine cartilage, the relationship between mechanical properties, molecular structure and cartilage composition has not been well studied. We adapted a recently developed AFM-based nano-rheology system to probe the dynamic nanomechanical properties of murine cartilage over a wide frequency range of 1 Hz to 10 kHz, and studied the role of glycosaminoglycan (GAG) on the dynamic modulus and poroelastic properties of murine femoral cartilage. We showed that poroelastic properties, highlighting fluid–solid interactions, are more sensitive indicators of loss of mechanical function compared to equilibrium properties in which fluid flow is negligible. These fluid-flow-dependent properties include the hydraulic permeability (an indicator of the resistance of matrix to fluid flow) and the high frequency modulus, obtained at high rates of loading relevant to jumping and impact injury in vivo. Utilizing a fibril-reinforced finite element model, we estimated the poroelastic properties of mouse cartilage over a wide range of loading rates for the first time, and show that the hydraulic permeability increased by a factor ~16 from k[subscript normal] = 7.80 × 10[superscript −16] ± 1.3 × 10[superscript −16] m[superscript 4]/N s to k[subscript GAG-depleted] = 1.26 × 10[superscript −14] ± 6.73 × 10[superscript −15] m[superscript 4]/N s after GAG depletion. The high-frequency modulus, which is related to fluid pressurization and the fibrillar network, decreased significantly after GAG depletion. In contrast, the equilibrium modulus, which is fluid-flow independent, did not show a statistically significant alteration following GAG depletion.National Institutes of Health (U.S.) (Grant 060331)Whitaker Foundation (Health Sciences Fund Fellowship)Arthritis Australi

Assessment of Effectiveness and Adverse Effect of New Combination Chemotherapy (irinotecan, cisplatin, and dexamethasone) in Relapse and Refractory Hodgkin Lymphoma

Background: Chemotherapy with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD regimen) cannot cure all patients with Hodgkin lymphoma. In this study, we evaluated the efficacy and adverse effect of a new regimen consist irinotecan, cisplatin, and dexamethasone (ICD) in relapsed and refractory Hodgkin lymphoma as the second to fifth line of treatment. Materials and Methods: We performed a retrospective study in 26 relapsed or refractory patients with Hodgkin lymphoma receiving at least the first-line chemotherapy regimen (ABVD) and (ICD) as salvage therapy in Thaleghany Hospital from 2012 to 2018. This regimen consisted of irinotecan 65mg/m2 D1, D8, cisplatin 30mg/m2 D1, D8, and dexamethasone 40mg D1, 2, 8, and 9 was administered every 3 weeks for 6 cycles.  Treatment was discontinued in cases of disease progression or severe toxicity. Response to treatment was evaluated after two cycles. Patients with complete and partial remission were candidate high dose chemotherapy and autologous stem cell transplantation. Twenty-four patients were enrolled in the study. The mean age of 22 patients was 31.5 (19-67) years. Seven patients (29.1%) were in the first recurrence, and 17 (70.8%) were in the second or subsequent recurrence. Results: According to this study, three patients (12.5%) had complete response, 13 (45%) had partial response, four (16.6%) had stable disease, and four (16.6%) had progressive disease. Nine patients (37.5%) received high-dose chemotherapy and autologous stem cell support after ICD regimen. None of the cycles of chemotherapy were delayed due to treatment-related adverse event. Overall survival after six months in all patients was 91%, and mortality rate was 8.3% at the end of the study. Conclusion: The goal of salvage chemotherapy in relapsed or refractory Hodgkin Lymphoma is achieving CR or PR preparation patients for stabilization with BMT. Thus, we recommend ICD as one of the most effective protocols with overall response rate of 66% in this population.