DEVELOPMENT OF CORTICAL GABA CIRCUITRY: IDENTIFYING PERIODS OF VULNERABILITY TO SCHIZOPHRENIA

The development of cognitive functioning is disrupted in many individuals who will later be diagnosed with schizophrenia, lagging behind healthy comparison subjects by 1-2 standard deviations at clinical onset. Cognitive dysfunction often appears years before clinical onset, is the best predictor of functional outcome, and is increasingly recognized as a central feature of schizophrenia. The domains of cognitive functioning affected in schizophrenia are mediated, at least in part, by prefrontal cortex (PFC) GABA neurons, which show molecular alterations in postmortem studies in schizophrenia. One common environmental risk factor for schizophrenia is chronic cannabis use, which disrupts cognitive function most prominently during adolescence, a time of flux in PFC circuitry that may be a sensitive period for the effects of cannabis use on neural circuit maturation. Parvalbumin (PV)-containing GABA neurons may be particularly vulnerable to risk factors for schizophrenia since they are altered in the disease, important for neural activity associated with cognitive functioning, and have a lengthy period of postnatal maturation. However, the nature of PV neuron subtype-specific developmental changes is not clear. Therefore, this dissertation focuses on understanding the timing of altered expression profiles of GABA-related mRNA levels in schizophrenia, the impact of chronic cannabis exposure during adolescence on GABA circuits of the monkey PFC, and the cell type-specific nature of postnatal maturation of influential GABAergic connections. Indeed, we find that the profile of GABA transmission markers in postmortem PFC tissue in schizophrenia can be explained by disrupted development of their mRNA levels; that chronic exposure to the psychoactive compound in cannabis during adolescence alters the GABAergic mRNA levels in monkey PFC; and that two populations of PV neurons have distinctive modes of maturation in monkey PFC

Pemahaman Aksara Jepang Dasar melalui Shoudo

Kegiatan pengabdian masyarakat di sekolah ini bermula dari banyaknya acara-acara kejepangan di sekolah-sekolah. Acara tersebut mengangkat budaya Jepang seperti anime, cosplay, film Jepang, dan masakan Jepang. Dari kondisi tersebut terlihat bahwa keingintahuan tentang budaya Jepang disekitar kampus sangat besar. Ditambah lagi dengan meningkatnya industri Jepang di sekitar wilayah Bekasi, seiring dengan meningkatnya penjualan makanan bernuansa kejepangan.  Untuk mengakomodir kondisi tersebut diadakanlah pengabdian penulisan huruf Jepang melalui shoudo atau kaligrafi Jepang. Dengan kegiatan ini diharapkan para siswa yang mempunyai keingintahuan untuk belajar Jepang, mempunyai pijakan yang kuat dengan menguasai huruf-huruf Jepang. Dalam mempelajari bahasa Jepang, huruf mempunyai peranan penting. Huruf-huruf bahasa Jepang adalah hiragana, katakana dan kanji. Kesemua huruf tersebut wajib dikuasai dalam mempelajari bahasa Jepang. Dalam shodou huruf-huruf tersebut dipakai untuk mengekspresikan keindahan aksara Jepang. Kata-kata seperti gunung・ yamaå±±, air・ mizu　水, dan tanah ・tsuchi 土merupakan bentuk-bentuk kanji sederhana yang dipergunakan dalam PkM ini. Siswa-siswi yang mengikuti PkM ini berjumlah 30 orang dibagi menjadi 6 kelompok. Hasil dari penulisan aksara Jepang, dipresentasikan di depan kelas, memaparkan kesulitan dalam penulisan melalui shoudou. Antusias mereka terlihat ketika pembelajaran berlangsung huruf-huruf yang mereka tulis, ditulis berulang-ulang sampai mereka benar-benar mengetahui dengan baik.

Endogenous neurosteroids influence synaptic GABA_Areceptors during post-natal development

GABA plays a key role in both embryonic and neonatal brain development. For example, during early neonatal nervous system maturation, synaptic transmission, mediated by GABA A receptors (GABA ARs), undergoes a temporally specific form of synaptic plasticity to accommodate the changing requirements of maturing neural networks. Specifically, the duration of miniature inhibitory postsynaptic currents (mIPSCs), resulting from vesicular GABA activating synaptic GABA ARs, is reduced, permitting neurones to appropriately influence the window for postsynaptic excitation. Conventionally, programmed expression changes to the subtype of synaptic GABA AR are primarily implicated in this plasticity. However, it is now evident that, in developing thalamic and cortical principal- and inter-neurones, an endogenous neurosteroid tone (eg, allopregnanolone) enhances synaptic GABA AR function. Furthermore, a cessation of steroidogenesis, as a result of a lack of substrate, or a co-factor, appears to be primarily responsible for early neonatal changes to GABAergic synaptic transmission, followed by further refinement, which results from subsequent alterations of the GABA AR subtype. The timing of this cessation of neurosteroid influence is neurone-specific, occurring by postnatal day (P)10 in the thalamus but approximately 1 week later in the cortex. Neurosteroid levels are not static and change dynamically in a variety of physiological and pathophysiological scenarios. Given that GABA plays an important role in brain development, abnormal perturbations of neonatal GABA AR-active neurosteroids may have not only a considerable immediate, but also a longer-term impact upon neural network activity. Here, we review recent evidence indicating that changes in neurosteroidogenesis substantially influence neonatal GABAergic synaptic transmission. We discuss the physiological relevance of these findings and how the interference of neurosteroid-GABA AR interaction early in life may contribute to psychiatric conditions later in life. </p

Pemahaman Penerjemahan Bagi Guru Bahasa Jepang di Wilayah 3 Cirebon dan Jabodetabek

Kegiatan pengabdian kepada masyarakat ini bertujuan untuk memberikan pengetahuan tentang penerjemahan dan stimulus kepada guru-guru bahasa Jepang yang mengajar di sekolah-sekolah Jabodetabek dan wilayah 3 Cirebon melalui Musyarawah Guru Mata Pelajaran atau disingkat MGMP. Terdapat 19 sekolah menengah atas yang mengikuti PkM ini. Dari kegiatan PkM ini diharapkan guru-guru pengajar bahasa Jepang dapat mentranfer pengetahuannya kepada siswa siswi didikannya. Materi yang dipergunakan dalam kegiatan ini diambil dari ujian kemampuan bahasa Jepang level 4 bagian dokkai (pemahaman bacaan). Penelitian ini menggunakan pendekatan kolaboratif, dimana kegiatan dibagi menjadi grup atau kelompok dalam menyelesaikan permasalahan. Pembelajaran kolaboratif digunakan agar setiap anggota kelompok ikut aktif dalam memberikan ide atau gagasannya terhadap permasalahan yang terjadi. Hasil dari kegiatan PkM ini adalah adanya masukan kata bahasa Indonesia dari satu kata bahasa Jepang, khususnya untuk kata-kata yang mempunyai unsur budaya. Kesepakatan dan keberterimaan kata yang dipakai menjadi poin penting dalam kegiatan pengabdian ini

Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A "central hub" in schizophrenia pathophysiology?

Accumulating evidence points to altered GABAergic parvalbumin-expressing interneurons and impaired myelin/axonal integrity in schizophrenia. Both findings could be due to abnormal neurodevelopmental trajectories, affecting local neuronal networks and long-range synchrony and leading to cognitive deficits. In this review, we present data from animal models demonstrating that redox dysregulation, neuroinflammation and/or NMDAR hypofunction (as observed in patients) impairs the normal development of both parvalbumin interneurons and oligodendrocytes. These observations suggest that a dysregulation of the redox, neuroimmune, and glutamatergic systems due to genetic and early-life environmental risk factors could contribute to the anomalies of parvalbumin interneurons and white matter in schizophrenia, ultimately impacting cognition, social competence, and affective behavior via abnormal function of micro- and macrocircuits. Moreover, we propose that the redox, neuroimmune, and glutamatergic systems form a "central hub" where an imbalance within any of these "hub" systems leads to similar anomalies of parvalbumin interneurons and oligodendrocytes due to the tight and reciprocal interactions that exist among these systems. A combination of vulnerabilities for a dysregulation within more than one of these systems may be particularly deleterious. For these reasons, molecules, such as N-acetylcysteine, that possess antioxidant and anti-inflammatory properties and can also regulate glutamatergic transmission are promising tools for prevention in ultra-high risk patients or for early intervention therapy during the first stages of the disease

Autonomic nervous system involvement in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a chronic pulmonary vascular disease characterized by increased pulmonary vascular resistance (PVR) leading to right ventricular (RV) failure. Autonomic nervous system involvement in the pathogenesis of PAH has been demonstrated several years ago, however the extent of this involvement is not fully understood. PAH is associated with increased sympathetic nervous system (SNS) activation, decreased heart rate variability, and presence of cardiac arrhythmias. There is also evidence for increased renin-angiotensin-aldosterone system (RAAS) activation in PAH patients associated with clinical worsening. Reduction of neurohormonal activation could be an effective therapeutic strategy for PAH. Although therapies targeting adrenergic receptors or RAAS signaling pathways have been shown to reverse cardiac remodeling and improve outcomes in experimental pulmonary hypertension (PH)-models, the effectiveness and safety of such treatments in clinical settings have been uncertain. Recently, novel direct methods such as cervical ganglion block, pulmonary artery denervation (PADN), and renal denervation have been employed to attenuate SNS activation in PAH. In this review, we intend to summarize the multiple aspects of autonomic nervous system involvement in PAH and overview the different pharmacological and invasive strategies used to target autonomic nervous system for the treatment of PAH

Accidental intradural injection during attempted epidural block -A case report-

Several cases of accidental subdural injection have been reported, but only few of them are known to be accidental intradural injection during epidural block. Therefore we would like to report our experience of accidental intradural injection. A 68-year-old female was referred to our pain clinic due to severe metastatic spinal pain. We performed a diagnostic epidural injection at T9/10 interspace under the C-arm guided X-ray view. Unlike the usual process of block, onset was delayed and sensory dermatomes were irregular range. We found out a dense collection of localized radio-opaque contrast media on the reviewed X-ray findings. These are characteristic of intradural injection and clearly different from the narrow wispy bands of contrast in the subdural space

Proof-of-concept study of compartmentalized lung ventilation using system for asymmetric flow regulation (SAFR)

Asymmetrical distribution of acute lung injury in mechanically ventilated patients can result in a heterogeneity of gas distribution between different regions, potentially worsening ventilation-perfusion matching. Furthermore, overdistension of healthier, more compliant lung regions can lead to barotrauma and limit the effect of increased PEEP on lung recruitment. We propose a System for Asymmetric Flow Regulation (SAFR) which, combined with a novel double lumen endobronchial tube (DLT) may offer individualized lung ventilation to the left and right lungs, better matching each lung's mechanics and pathophysiology. In this preclinical experimental model, the performance of SAFR on gas distribution in a two-lung simulation system was tested. Our results indicate that SAFR may be a technically feasible and potentially clinically useful although further research is warranted

Recurrent ventricular tachycardia after cardiac sympathetic denervation: Prolonged cycle length with improved hemodynamic tolerance and ablation outcomes

IntroductionCardiac sympathetic denervation (CSD) is utilized for the management of ventricular tachycardia (VT) in structural heart disease when refractory to radiofrequency ablation (RFA) or when patient/VT characteristics are not conducive to RFA.MethodsWe studied consecutive patients who underwent CSD at our institution from 2009 to 2018 with VT requiring repeat RFA post-CSD. Patient demographics, VT/procedural characteristics, and outcomes were assessed.ResultsNinety-six patients had CSD, 16 patients underwent RFA for VT post-CSD. There were 15 male and 1 female patients with mean age of 54.2 ± 13.2 years. Fourteen patients had nonischemic cardiomyopathy. A mean of 2.0 ± 0.8 RFAs for VT was unsuccessful before the patient undergoing CSD. The median time between CSD and RFA was 104 days (interquartile range [IQR] = 15-241). The clinical VT cycle length was significantly increased after CSD both spontaneously on ECG and/or ICD interrogation (355 ± 73 ms pre-CSD vs. 422 ± 94 ms post-CSD, p = .001) and intraprocedurally (406 ± 86 ms pre-CSD vs. 457 ± 88 ms post-CSD, p = .03). Two patients had polymorphic and 14 had monomorphic VT (MMVT) pre-CSD, and all patients had MMVT post-CSD. The proportion of mappable, hemodynamically stable VTs increased from 35% during pre-CSD RFA to 58% during post-CSD RFA (p = .038). At median follow-up of 413 days (IQR = 43-1840) after RFA, eight patients had no further VT.ConclusionRFA for recurrent MMVT post-CSD is a reasonable treatment option with intermediate-term clinical success in 50% of patients. Clinical VT cycle length was significantly increased after CSD with associated improvement in mappable, hemodynamically tolerated VT during RFA