Pathogenic SCN2A variants cause early-stage dysfunction in patient-derived neurons.

Pathogenic heterozygous variants in SCN2A, which encodes the neuronal sodium channel NaV1.2, cause different types of epilepsy or intellectual disability (ID)/autism without seizures. Previous studies using mouse models or heterologous systems suggest that NaV1.2 channel gain-of-function typically causes epilepsy, whereas loss-of-function leads to ID/autism. How altered channel biophysics translate into patient neurons remains unknown. Here, we investigated iPSC-derived early-stage cortical neurons from ID patients harboring diverse pathogenic SCN2A variants [p.(Leu611Valfs*35); p.(Arg937Cys); p.(Trp1716*)] and compared them with neurons from an epileptic encephalopathy (EE) patient [p.(Glu1803Gly)] and controls. ID neurons consistently expressed lower NaV1.2 protein levels. In neurons with the frameshift variant, NaV1.2 mRNA and protein levels were reduced by ~ 50%, suggesting nonsense-mediated decay and haploinsufficiency. In other ID neurons, only protein levels were reduced implying NaV1.2 instability. Electrophysiological analysis revealed decreased sodium current density and impaired action potential (AP) firing in ID neurons, consistent with reduced NaV1.2 levels. In contrast, epilepsy neurons displayed no change in NaV1.2 levels or sodium current density, but impaired sodium channel inactivation. Single-cell transcriptomics identified dysregulation of distinct molecular pathways including inhibition of oxidative phosphorylation in neurons with SCN2A haploinsufficiency and activation of calcium signaling and neurotransmission in epilepsy neurons. Together, our patient iPSC-derived neurons reveal characteristic sodium channel dysfunction consistent with biophysical changes previously observed in heterologous systems. Additionally, our model links the channel dysfunction in ID to reduced NaV1.2 levels and uncovers impaired AP firing in early-stage neurons. The altered molecular pathways may reflect a homeostatic response to NaV1.2 dysfunction and can guide further investigations.

Experience of cyclone Gonu in the Islamic Republic of Iran: lessons learned.

Gonu, the second tropical cyclone of the 2007 northern Indian ocean cyclone season, affected Oman, Pakistan, the United Arab Emirates and the Islamic Republic of Iran. This report examines the effects of cyclone Gonu in the Islamic Republic of Iran where it approached on its path on 6 June 2007 and reviews the actions taken before, during and after the cyclone. The incident highlighted the need for a special protocol to be prepared for all types of natural disasters. Responsible organizations should train their personnel according to the prepared protocols and service packages. Among the important lessons learned were the need for early warning, proper community involvement, access to essential data for risk analysis, special attention to safety of infrastructures, coordination and command integrity.

Anxiety, depression and health-related quality of life in those injured by landmines, Ilam, Islamic Republic of Iran.

We assessed depression, anxiety and health-related quality of life (HRQOL) in 137 cases of landmine injury in Ilam province, using the Hospital Anxiety & Depression Scale (HADS) and the Short Form Health Survey (SF36) questionnaires. We also compared their scores with an uninjured control group (n = 360). Most of the injured were male (93.4%) and illiterate (54.7%) with some irreversible sequelae (86.9%). Overall, 69.3% of the injured participants scored high for both anxiety and depression. The level of anxiety and depression was significantly higher in older cases, those not completely recovered compared with recovered cases and those with amputation compared with those without amputation. The injured also had significantly lower mean scores in all HRQOL components than the control group. Landmine injured should be monitored for early identification and treatment of depression and anxiety.

Experience of cyclone Gonu in the Islamic Republic of Iran: lessons learned

Gonu, the second tropical cyclone of the 2007 northern Indian ocean cyclone season, affected Oman, Pakistan, the United Arab Emirates and the Islamic Republic of Iran. This report examines the effects of cyclone Gonu in the Islamic Republic of Iran where it approached on its path on 6 June 2007 and reviews the actions taken before, during and after the cyclone. The incident highlighted the need for a special protocol to be prepared for all types of natural disasters. Responsible organizations should train their personnel according to the prepared protocols and service packages. Among the important lessons learned were the need for early warning, proper community involvement, access to essential data for risk analysis, special attention to safety of infrastructures, coordination and command integrity