In this study, we systematically tested the hypothesis that during the critical developmental period of adolescence, on a macro scale, the concentrations of major excitatory and inhibitory neurotransmitters (glutamate/glutamine and γ‑aminobutyric acid [GABA]) in the dorsal and ventral lateral prefrontal cortex are associated with the brain's functional connectivity and an individual's psychopathology. Neurotransmitters were measured via magnetic resonance spectroscopy while functional connectivity was measured with resting-state fMRI (n = 121). Seed-based and network-based analyses revealed associations of neurotransmitter concentrations and functional connectivities between regions/networks that are connected to prefrontal cortices via structural connections that are thought to be under dynamic development during adolescence. These regions tend to be boundary areas between functional networks. Furthermore, several connectivities were found to be associated with individual's levels of internalizing psychopathology. These findings provide insights into specific neurochemical mechanisms underlying the brain's macroscale functional organization, its development during adolescence, and its potential associations with symptoms associated with internalizing psychopathology.
Humans ; Adolescent ; Glutamic Acid/metabolism* ; Prefrontal Cortex/diagnostic imaging* ; Male ; Glutamine/metabolism* ; Female ; gamma-Aminobutyric Acid/metabolism* ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Nerve Net/metabolism* ; Neural Pathways ; Connectome

Direct electrical stimulation of the human cortex can produce subjective visual sensations, yet these sensations are unstable. The underlying mechanisms may stem from differences in electrophysiological activity within the distributed network outside the stimulated site. To address this problem, we recruited 69 patients who experienced visual sensations during invasive electrical stimulation while intracranial electroencephalography (iEEG) data were recorded. We found significantly flattened power spectral slopes in distributed regions involving different brain networks and decreased integrated information during elicited visual sensations compared with the non-sensation condition. Further analysis based on minimum information partitions revealed that the reconfigured network interactions primarily involved the inferior frontal cortex, posterior superior temporal sulcus, and temporoparietal junction. The flattened power spectral slope in the inferior frontal gyrus was also correlated with integrated information. Taken together, this study indicates that the altered electrophysiological signatures provide insights into the neural mechanisms underlying subjective visual sensations.
Humans ; Male ; Female ; Adult ; Visual Perception/physiology* ; Electric Stimulation ; Middle Aged ; Young Adult ; Electrocorticography ; Electroencephalography ; Brain Mapping

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Animals ; Mice ; Colon ; Histological Techniques

SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic. As part of the innate immune response to viral infection, type I interferons (IFN-I) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes (ISGs), that collectively foster an antiviral state. We report here the identification of a group of type I interferon suppressed genes, including fatty acid synthase (FASN), which are involved in lipid metabolism. Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection. More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern. Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type I interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19.

Background: Among the various glycemic indices in current use, glycemic variability has the greatest contribution in the development of microvascular and macrovascular complications in Type 2 Diabetes mellitus (T2DM). Most metrics that are currently used to measure glycemic variability are derived from continuous glucose monitoring (CGM) data. However, CGM is burdensome to the patient due to its relatively high cost as well as the need for multiple visits with the health care provider. With the use of serum 1,5-anhydroglucitol (1,5-AG) as a biomarker of glucose fluctuations, physicians and patients alike could have an easier surrogate measure of glycemic variability thus aiding in achieving target glucose control. This study aims to determine the diagnostic accuracy of 1,5-AG as compared to the glycemic variability metrics derived from CGM as a surrogate measure of glycemic variability among adult Filipinos with T2DM. Methods: Retrospective analysis of data of adult patients aged 20 years old and above diagnosed with T2DM referred for CGM at the Diabetes, Endocrine, Metabolic, and Nutrition Center of Cardinal Santos Medical Center from January 2017 to October 2021 who underwent serum 1,5-AG level determination within 2 weeks of CGM were collected. Diagnostic accuracy was obtained by computing the sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and Youden index. Pearson correlation coefficient was used to determine the correlation of 1,5-AG and the different metrics. Analysis of variance (ANOVA) was used to check for statistical significance with 99% confidence interval and a p < 0.05 considered as statistically significant. Results: This study involving 37 subjects showed a good diagnostic accuracy of serum 1,5-AG levels with the different measures of glycemic variability derived from CGM namely mean amplitude of glycemic excursion (MAGE), continuous overlapping net glycemic action at 1-hour intervals (CONGA-1), and mean of daily differences (MODD) with significant correlation among patients with HbA1c ≤ 7%. Subjects were on CGM for approximately 6 ± 1 day with statistically significant difference between the good and poor glucose control group (p<0.05). Determination of diagnostic accuracy between 1,5- AG and MAGE showed good accuracy (Sensitivity = 95.3%, Specificity = 100%, PPV = 100%, NPV = 75.43%, Diagnostic accuracy 96%, and a Youden Index of 92.3) with a statistically significant correlation among subjects with HbA1c level ≤ 7% (p=0.021). There is likewise good diagnostic accuracy between CONGA-1 and 1,5-AG level (Sensitivity = 99%, Specificity = 75.29%, PPV = 89.1%, NPV = 97%, Accuracy = 89.50% and Youden index of 58.41) with a statistically significant correlation among subjects with HbA1c ≤ 7% (p=0.038). Comparison with interday glycemic variability showed fair diagnostic accuracy between MODD and 1,5-AG (Sensitivity = 79.17%, Specificity = 78%, PPV = 97%, NPV = 32%, Accuracy = 76.89%, and Youden index of 49.07) and a statistically significant correlation among subjects with HbA1c ≤ 7% (p=0.009). Conclusion There is good diagnostic accuracy of serum 1,5-AG levels with the different measures of glycemic variability derived from CGM namely MAGE, CONGA-1, and MODD with significant correlation among patients with HbA1c ≤ 7%. Among diabetics with HbA1c ≤7%, 1,5-AG could be used as a surrogate measure of glycemic variability and excursions.
Diabetes Mellitus, Type 2

Non-traumatic osteonecrosis of the femoral head (ONFH) usually affects adults younger than 50 years and frequently leads to femoral head collapse and subsequent arthritis of the hip.It is becoming more prevalent along with increasing use of corticosteroids for the adjuvant therapy of leukemia and other myelogenous diseases as well as management of organ transplantation. This review updated knowledge on the pathogenesis, classification criteria, staging system, and treatment of ONFH.

Many azoospermic men do not possess mature spermatozoa at the time of surgical sperm extraction. This study is a systematic review and meta-analysis evaluating outcomes following round spermatid injection (ROSI), a technique which utilizes immature precursors of spermatozoa for fertilization. An electronic search was performed to identify relevant articles published through October 2018. Human cohort studies in English involving male patients who had round spermatids identified and used for fertilization with human oocytes were included. Fertilization rate, pregnancy rate, and resultant delivery rate were assessed following ROSI. Meta-analysis outcomes were analyzed using a random-effects model. Data were extracted from 22 studies involving 1099 couples and 4218 embryo transfers. The fertilization rate after ROSI was 38.7% (95% confidence interval [CI]: 31.5%-46.3%), while the pregnancy rate was 3.7% (95% CI: 3.2%-4.4%). The resultant delivery rate was low, with 4.3% of embryo transfers resulting in a delivery (95% CI: 2.3%-7.7%). The pregnancy rate per couple was 13.4% (95% CI: 6.8%-19.1%) and the resultant delivery rate per couple was 8.1% (95% CI: 6.1%-14.4%). ROSI has resulted in clinical pregnancies and live births, but success rates are considerably lower than those achieved with mature spermatozoa. While this technique may be a feasible alternative for men with azoospermia who decline other options, couples should be aware that the odds of a successful delivery are greatly diminished and the prognosis is relatively poor.

Non-traumatic osteonecrosis of the femoral head (ONFH) usually affects adults younger than 50 years and frequently leads to femoral head collapse and subsequent arthritis of the hip.It is becoming more prevalent along with increasing use of corticosteroids for the adjuvant therapy of leukemia and other myelogenous diseases as well as management of organ transplantation. This review updated knowledge on the pathogenesis, classification criteria, staging system, and treatment of ONFH.

A correction to this paper has been published: https://doi.org/10.1007/s12264-021-00695-8.