The rumen microbiota contributed to the development of mastitis induced by subclinical ketosis.

BACKGROUND: Mastitis is a serious disease which affects animal husbandry, particularly in cow breeding. The etiology of mastitis is complex and its pathological mechanism is not yet fully understood. Our previous research in clinical investigation has revealed that subclinical ketosis can increase the number of somatic cell counts (SCC) in milk, although the underlying mechanism remains unclear. Recent studies have further confirmed the significant role of mastitis. RESULTS: In this study, we aimed to examine the SCC, rumen microbiota, and metabolites in the milkmen of cows with subclinical ketosis. Additionally, we conducted a rumen microbiota transplant into mice to investigate the potential association between rumen microbiota disturbance and mastitis induced by subclinical ketosis in dairy cows. The study has found that cows with subclinical ketosis have a higher SCC in their milk compared to healthy cows. Additionally, there were significant differences in the rumen microbiota and the level of volatile fatty acid (VFA) between cows with subclinical ketosis and healthy cows. Moreover, transplanting the rumen microbiota from subclinical ketosis and mastitis cows into mice can induce mammary inflammation and liver function damage than transplanting the rumen flora from healthy dairy cows. CONCLUSIONS: In addition to the infection of mammary gland by pathogenic microorganisms, there is also an endogenous therapeutic pathway mediated by rumen microbiota. Targeted rumen microbiota modulation may be an effective way to prevent and control mastitis in dairy cows.

Negative family body talk and negative emotional eating among Chinese adolescent girls and young adult women: The role of body dissatisfaction and feminism consciousness.

Negative emotional eating has been increasingly a prominent disordered eating and public health problem among young women, especially during COVID-19. Although previous studies have attempted to explain the relationship between body talk and negative emotional eating, limited studies focused on examining the potential mechanisms, especially the potential protective mechanism. Thus, the current study aimed to examine the relationship between negative family body talk (NFBT) and negative emotional eating, as well as its underlying mechanism - the mediating role of body dissatisfaction (BDIS) and the moderating role of feminism consciousness (FC). A cross-sectional study was employed among a sample of Chinese girls and young women (n = 813, Mage = 19.4 years) from a junior college in central China. Participants completed surveys assessing NFBT (Adapted Body Talk Scale), BDIS (Body Image State Scale), negative emotional eating (Dutch Eating Behavior Questionnaire), and FC (Synthesis Subscale from Feminist Identity Composite). A moderated mediation analysis was conducted. The results showed that: (1) after controlling for age and BMI, NFBT was positively associated with negative emotional eating, and BDIS could significantly mediate this relationship (mediating effect = 0.03, 95% CI [0.02, 0.06]); (2) FC significantly moderated both the direct relationship between NFBT and negative emotional eating and the relationship between NFBT and BDIS. Specifically, these two associations were not significant for participants with higher FC (+1SD above average). This study deepens our understanding of the relationship between NFBT and negative emotional eating, as well as the protective role of FC. If future studies demonstrate causal relationships, this evidence could point to a need for programs to prevent negative emotional eating in young women by increasing their level of feminism consciousness.

ZEA mediates autophagy through the ROS-AMPK-m-TOR pathway to enhance the susceptibility of mastitis induced by Staphylococcus aureus in mice.

Mastitis is an inflammatory response of the mammary tissue caused by pathogenic bacterial infections, especially Staphylococcus aureus (S. aureus). Zearalenone (ZEA) is one of the common mycotoxins in moldy feed, which usually affects the cow's resistance to pathogenic microorganisms. However, it is not well understood whether ZEA affects the development of mastitis. Therefore, this study aimed to investigate the role of ZEA in the development of S. aureus-induced mastitis in mice. The results showed that administered daily by gavage for one week of ZEA (40 mg/kg) aggravated the severity of mastitis induced by S. aureus. Furthermore, we found that ZEA promotes the adhesion and invasion of S. aureus into mouse mammary epithelial cells (MMEC) by activating autophagy, and the activation of autophagy mediated by ROS-AMPK-m-TOR pathway. Taken together, the results showed that ZEA enhances S. aureus-induced mastitis susceptibility through activating autophagy mediated by ROS-AMPK-mTOR signaling pathway.

A Review of Homomorphic Encryption for Privacy-Preserving Biometrics.

The advancement of biometric technology has facilitated wide applications of biometrics in law enforcement, border control, healthcare and financial identification and verification. Given the peculiarity of biometric features (e.g., unchangeability, permanence and uniqueness), the security of biometric data is a key area of research. Security and privacy are vital to enacting integrity, reliability and availability in biometric-related applications. Homomorphic encryption (HE) is concerned with data manipulation in the cryptographic domain, thus addressing the security and privacy issues faced by biometrics. This survey provides a comprehensive review of state-of-the-art HE research in the context of biometrics. Detailed analyses and discussions are conducted on various HE approaches to biometric security according to the categories of different biometric traits. Moreover, this review presents the perspective of integrating HE with other emerging technologies (e.g., machine/deep learning and blockchain) for biometric security. Finally, based on the latest development of HE in biometrics, challenges and future research directions are put forward.

A Secure Online Fingerprint Authentication System for Industrial IoT Devices over 5G Networks.

The development of 5G networks has rapidly increased the use of Industrial Internet of Things (IIoT) devices for control, monitoring, and processing purposes. Biometric-based user authentication can prevent unauthorized access to IIoT devices, thereby safeguarding data security during production. However, most biometric authentication systems in the IIoT have no template protection, thus risking raw biometric data stored as templates in central databases or IIoT devices. Moreover, traditional biometric authentication faces slow, limited database holding capacity and data transmission problems. To address these issues, in this paper we propose a secure online fingerprint authentication system for IIoT devices over 5G networks. The core of the proposed system is the design of a cancelable fingerprint template, which protects original minutia features and provides privacy and security guarantee for both entity users and the message content transmitted between IIoT devices and the cloud server via 5G networks.Compared with state-of-the-art methods, the proposed authentication system shows competitive performance on six public fingerprint databases, while saving computational costs and achieving fast online matching.

Social Exclusion and Depression among undergraduate students: the mediating roles of rejection sensitivity and social self-efficacy.

Nowadays, depression has been a prominent mental health problem throughout the world. A common but negative social experience, social exclusion (also known as ostracism) is a great risk factor for individuals' health and adaptation. Undergraduate students are in a development period of challenges and transitions, so they are vulnerable to suffering from depression and negative social experiences. Against this background, the present study aimed to examine the association between social exclusion and undergraduate students' depression as well as the underlying mechanism - the mediating roles of rejection sensitivity and social self-efficacy. Seven hundred sixty-two undergraduate students were recruited to participate in this study, who were asked to complete a set of questionnaires measuring social exclusion, depression, rejection sensitivity, and social self-efficacy. After controlling for gender, social exclusion was positively associated with undergraduate students' depression. And rejection sensitivity and social self-efficacy could significantly mediate this relation through three mediating paths - the separate mediating effects of rejection sensitivity and social self-efficacy, as well as the serial mediating effect of rejection sensitivity and social self-efficacy. These results could not only deepen our understanding of this theme, but also have several practical implications for the intervention of depression, for example, relevant social skill training and cognitive therapy could be adopted to intervene the rejection sensitivity and social self-efficacy.

An Energy-Efficient and Secure Data Inference Framework for Internet of Health Things: A Pilot Study.

Privacy protection in electronic healthcare applications is an important consideration, due to the sensitive nature of personal health data. Internet of Health Things (IoHT) networks that are used within a healthcare setting have unique challenges and security requirements (integrity, authentication, privacy, and availability) that must also be balanced with the need to maintain efficiency in order to conserve battery power, which can be a significant limitation in IoHT devices and networks. Data are usually transferred without undergoing filtering or optimization, and this traffic can overload sensors and cause rapid battery consumption when interacting with IoHT networks. This poses certain restrictions on the practical implementation of these devices. In order to address these issues, this paper proposes a privacy-preserving two-tier data inference framework solution that conserves battery consumption by inferring the sensed data and reducing data size for transmission, while also protecting sensitive data from leakage to adversaries. The results from experimental evaluations on efficiency and privacy show the validity of the proposed scheme, as well as significant data savings without compromising data transmission accuracy, which contributes to energy efficiency of IoHT sensor devices.

Biometrics for Internet-of-Things Security: A Review.

The large number of Internet-of-Things (IoT) devices that need interaction between smart devices and consumers makes security critical to an IoT environment. Biometrics offers an interesting window of opportunity to improve the usability and security of IoT and can play a significant role in securing a wide range of emerging IoT devices to address security challenges. The purpose of this review is to provide a comprehensive survey on the current biometrics research in IoT security, especially focusing on two important aspects, authentication and encryption. Regarding authentication, contemporary biometric-based authentication systems for IoT are discussed and classified based on different biometric traits and the number of biometric traits employed in the system. As for encryption, biometric-cryptographic systems, which integrate biometrics with cryptography and take advantage of both to provide enhanced security for IoT, are thoroughly reviewed and discussed. Moreover, challenges arising from applying biometrics to IoT and potential solutions are identified and analyzed. With an insight into the state-of-the-art research in biometrics for IoT security, this review paper helps advance the study in the field and assists researchers in gaining a good understanding of forward-looking issues and future research directions.

A Cancelable Iris- and Steganography-Based User Authentication System for the Internet of Things.

Remote user authentication for Internet of Things (IoT) devices is critical to IoT security, as it helps prevent unauthorized access to IoT networks. Biometrics is an appealing authentication technique due to its advantages over traditional password-based authentication. However, the protection of biometric data itself is also important, as original biometric data cannot be replaced or reissued if compromised. In this paper, we propose a cancelable iris- and steganography-based user authentication system to provide user authentication and secure the original iris data. Most of the existing cancelable iris biometric systems need a user-specific key to guide feature transformation, e.g., permutation or random projection, which is also known as key-dependent transformation. One issue associated with key-dependent transformations is that if the user-specific key is compromised, some useful information can be leaked and exploited by adversaries to restore the original iris feature data. To mitigate this risk, the proposed scheme enhances system security by integrating an effective information-hiding technique-steganography. By concealing the user-specific key, the threat of key exposure-related attacks, e.g., attacks via record multiplicity, can be defused, thus heightening the overall system security and complementing the protection offered by cancelable biometric techniques.

Cytoplasmic sequestration of FUS/TLS associated with ALS alters histone marks through loss of nuclear protein arginine methyltransferase 1.

Mutations in the RNA-binding protein FUS/TLS (FUS) have been linked to the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Although predominantly nuclear, this heterogenous nuclear ribonuclear protein (hnRNP) has multiple functions in RNA processing including intracellular trafficking. In ALS, mutant or wild-type (WT) FUS can form neuronal cytoplasmic inclusions. Asymmetric arginine methylation of FUS by the class 1 arginine methyltransferase, protein arginine methyltransferase 1 (PRMT1), regulates nucleocytoplasmic shuttling of FUS. In motor neurons of primary spinal cord cultures, redistribution of endogenous mouse and that of ectopically expressed WT or mutant human FUS to the cytoplasm led to nuclear depletion of PRMT1, abrogating methylation of its nuclear substrates. Specifically, hypomethylation of arginine 3 of histone 4 resulted in decreased acetylation of lysine 9/14 of histone 3 and transcriptional repression. Distribution of neuronal PRMT1 coincident with FUS also was detected in vivo in the spinal cord of FUS(R495X) transgenic mice. However, nuclear PRMT1 was not stable postmortem obviating meaningful evaluation of ALS autopsy cases. This study provides evidence for loss of PRMT1 function as a consequence of cytoplasmic accumulation of FUS in the pathogenesis of ALS, including changes in the histone code regulating gene transcription.

A compartmentalized culture device for studying the axons of CNS neurons.

We report here the development of a compartmentalized culture device that allows the spatial separation of the somatodendrites and axons of central nervous system (CNS) neurons. The device consists of two compartments separated by a septum constructed by attaching a porous polycarbonate track etch (PCTE) filter on top of a microchannel-filled polydimethylsiloxane (PDMS) membrane. The surface and microchannels of the septum are coated and filled, respectively, with materials that support neuron growth and neurite migration. When rat hippocampal neurons are cultured in the top compartment, axons are the only processes that can migrate through the septum to the bottom compartment. The axons in the bottom compartment can be studied directly in real-time or through immunofluorescence staining after fixation. Axons containing ∼3 µg protein can be isolated from each device for biochemical analyses. In addition, the septum also impedes the movement of small molecules between the top and bottom compartments. This feature allows the somatodendrites and axons of neurons, which occupy the top and bottom compartments of the device, respectively, to be manipulated independently. The potential applications of the device as a tool in diverse studies concerning neuronal axons and in screening reagents that regulate axonal functions have also been discussed.

[Pharmacokinetics of SN-38 in rats and tissue distribution of 7-ethyl-10-hydroxycamptothecin in mice after intravenous injection of irinotecan hydrochloride nanoparticles].

The paper reported an investigation of the pharmacokinetics of SN-38 (7-ethyl-10-hydroxy-camptothecin) in rats and the tissue distribution in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11) via tail veins. An LC-MS/MS method was established to determine the concentrations of SN-38 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of SN-38 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with irinotecan solution, the elimination half-life of SN-38 was prolonged from 2.17 h to 2.67 h after the intravenous injection of CPT-11 NPs, but its AUC had little change. After the injection of CPT-11 NPs in mice, over time, the concentrations of CPT-11-metabolized SN-38 in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, followed by in the spleen and liver, but those in the heart and brain had no change. However, the amount of SN-38 in the kidneys was reduced with time. CPT-11 NPs could prolong SN-38's (one of its metabolites) blood circulation time in rats and significantly increased the concentration of CPT-11-metabolized SN-38 in the whole blood, colon and lungs of mice. CPT-11 NPs made SN-38 efficiently target-bind to the colon and lungs of mice.

Comparative experimental study of the biomechanical properties of retrograde tibial nailing and distal tibia plate in distal tibia fracture.

Objective: A biomechanical comparative analysis was conducted to evaluate the retrograde tibial nailing (RTN) and distal tibia plate techniques for the treatment of distal tibia fractures. Methods: Fourteen fresh adult tibia specimens were selected, consisting of seven males and seven females aged 34-55 years. The specimens were randomly divided into two groups (Group A and Group B) using a numerical table method, with seven specimens in each group. Group A underwent internal fixation of distal tibial fractures using RTN, while Group B received internal fixation using a plate. The axial compression properties of the specimens were tested in the neutral positions under pressures of 100, 200, 300, 400, and 500 N. Additionally, the torsional resistance of the two groups was assessed by subjecting the specimens to torques of 1.0, 2.0, 3.0, 4.0, and 5.0 N m. Results: At pressures of 400 and 500 N, the axial compression displacement in Group A (1.11 ± 0.06, 1.24 ± 0.05) mm was significantly smaller than that in Group B (1.21 ± 0.08, 1.37 ± 0.11) mm (p = 0.023, 0.019). Moreover, at a pressure of 500 N, the axial compression stiffness in Group A (389.24 ± 17.79) N/mm was significantly higher than that of the control group (362.37 ± 14.44) N/mm (p = 0.010). When subjected to torques of 4 and 5 N m, the torsion angle in Group A (2.97° ± 0.23°, 3.41° ± 0.17°) was significantly smaller compared to Group B (3.31° ± 0.28°, 3.76° ± 0.20°) (p = 0.035, 0.004). Furthermore, at a torque of 5 N m, the torsional stiffness in Group A (1.48 ± 0.07) N m/° was significantly higher than that in Group B (1.36 ± 0.06) N·m/° (p = 0.003). Conclusion: The results obtained from the study demonstrate that the biomechanical performance of RTN outperforms that of the distal tibial plate, providing valuable biomechanical data to support the clinical implementation of RTN.

Lightweight federated learning for STIs/HIV prediction.

This paper presents a solution that prioritises high privacy protection and improves communication throughput for predicting the risk of sexually transmissible infections/human immunodeficiency virus (STIs/HIV). The approach utilised Federated Learning (FL) to construct a model from multiple clinics and key stakeholders. FL ensured that only models were shared between clinics, minimising the risk of personal information leakage. Additionally, an algorithm was explored on the FL manager side to construct a global model that aligns with the communication status of the system. Our proposed method introduced Random Forest Federated Learning for assessing the risk of STIs/HIV, incorporating a flexible aggregation process that can be adjusted to accommodate the capacious communication system. Experimental results demonstrated the significant potential of a solution for estimating STIs/HIV risk. In comparison with recent studies, our approach yielded superior results in terms of AUC (0.97) and accuracy ( 93 % ). Despite these promising findings, a limitation of the study lies in the experiment for man's data, due to the self-reported nature of the data and sensitive content. which may be subject to participant bias. Future research could check the performance of the proposed framework in partnership with high-risk populations (e.g., men who have sex with men) to provide a more comprehensive understanding of the proposed framework's impact and ultimately aim to improve health outcomes/health service optimisation.

[Pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in Beagle dogs].

The object of this study is to investigate the pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in healthy adult Beagle dogs following single and multiple oral dose administration. A randomized, cross-over study was conducted with nine healthy adult Beagle dogs assigned to three groups. Each group was arranged to take atorvastatin calcium (A), pioglitazone hydrochloride (B), atorvastatin calcium and pioglitazone hydrochloride (C) orally in the first period, to take B, C, A in the second period, and to take C, A, B in the third period for 6 days respectively. The blood samples were collected at the first and the sixth day after the administration, plasma drug concentrations were determined by LC-MS/MS, a one-week wash-out period was needed between each period. The pharmacokinetic parameters of drug combination group and the drug alone group were calculated by statistical moment method, calculation of C(max) and AUC(0-t) was done by using 90% confidence interval method of the bioequivalence and bioavailability degree module DAS 3.2.1 software statistics. Compared with the separate administration, the main pharmacokinetic parameters (C(max) and AUC(0-t)) of joint use of pioglitazone hydrochloride and atorvastatin calcium within 90% confidence intervals for bioequivalence statistics were unqualified, the mean t(max) with standard deviation used paired Wilcoxon test resulted P > 0.05. There was no significant difference within t1/2, CL(int), MRT, V/F. Pioglitazone hydrochloride and atorvastatin calcium had pharmacokinetic interaction in healthy adult Beagle dogs.

A review of multi-factor authentication in the Internet of Healthcare Things.

Objective: This review paper aims to evaluate existing solutions in healthcare authentication and provides an insight into the technologies incorporated in Internet of Healthcare Things (IoHT) and multi-factor authentication (MFA) applications for next-generation authentication practices. Our review has two objectives: (a) Review MFA based on the challenges, impact and solutions discussed in the literature; and (b) define the security requirements of the IoHT as an approach to adapting MFA solutions in a healthcare context. Methods: To review the existing literature, we indexed articles from the IEEE Xplore, ACM Digital Library, ScienceDirect, and SpringerLink databases. The search was refined to combinations of 'authentication', 'multi-factor authentication', 'Internet of Things authentication', and 'medical authentication' to ensure that the retrieved journal articles and conference papers were relevant to healthcare and Internet of Things-oriented authentication research. Results: The concepts of MFA can be applied to healthcare where security can often be overlooked. The security requirements identified result in stronger methodologies of authentication such as hardware solutions in combination with biometric data to enhance MFA approaches. We identify the key vulnerabilities of weaker approaches to security such as password use against various cyber threats. Cyber threats and MFA solutions are categorised in this paper to facilitate readers' understanding of them in healthcare domains. Conclusions: We contribute to an understanding of up-to-date MFA approaches and how they can be improved for use in the IoHT. This is achieved by discussing the challenges, benefits, and limitations of current methodologies and recommendations to improve access to eHealth resources through additional layers of security.

Degradation of Zearalenone by Dielectric Barrier Discharge Cold Plasma and Its Effect on Maize Quality.

In this study, a dielectric barrier discharge (DBD) cold plasma was used to degrade zearalenone, and the degradation efficiency and the quality of maize were evaluated. The results showed that the zearalenone degradation rates increased with the increase in voltage and time. When it was treated at 50 KV for 120 s, the degradation percentage of the zearalenone in maize could reach 56.57%. The kinetics' analysis showed that the degradation followed a first-order reaction. The crude fiber of the maize reduced after the cold plasma treatment. In addition, cold plasma treatment did not significantly change the crude protein content, but slightly changed the fatty acid and color. The changes in maize quality are generally acceptable. DBD cold plasma may be a promising approach to reducing zearalenone in maize.

Parental Phubbing and Adolescent Depressive Symptoms during COVID-19: A Serial Meditating Model.

BACKGROUND: During the COVID-19 pandemic, depressive symptoms, a common emotional problem among adolescents, have become more prominent. Regarding the influencing factors of adolescent depressive symptoms, it is widely accepted that parents' problematic cellphone use around the family (specifically parental phubbing) is a strong predictive factor for the development of depressive symptoms among adolescents. Notably, the COVID-19 pandemic caused a sharp increase in the number of individuals with depressive symptoms, and the negative consequences of parental phubbing and depressive symptoms might have been exacerbated. Accordingly, this study aimed to examine the association between parental phubbing and adolescent depressive symptoms as well as their underlying mechanism. METHOD: To test our hypotheses, we conducted an offline/online survey with 614 adolescents in Central China from May to June 2022, which corresponded to a period of strict lockdowns in some areas due to the outbreak of the Omicron variant. The participants completed a set of measures, including a technology interference questionnaire, a parent-child relationship scale, a self-concept clarity scale, and the depressive symptoms scale. RESULTS: Parental phubbing was positively associated with adolescent depressive symptoms; the parent-child relationship and self-concept clarity could independently mediate this relationship; and the parent-child relationship and self-concept clarity were also serial mediators in this association. These findings extend previous research by highlighting the impact of parental technology use on their children and the underlying mechanism explaining adolescent depressive symptoms. They provide practical recommendations for parents to prioritize fostering a positive family environment and minimizing phubbing behaviors to enhance adolescent development, particularly in the context of the COVID-19 pandemic.

Effect of the Similarity of Formulations and Excipients of Approved Generic Drug Products on In Vivo Bioequivalence for Putative Biopharmaceutics Classification System Class III Drugs.

One of the potential essential factors that restricts generic industry from applying the Biopharmaceutics Classification System (BCS) Class III biowaiver is adherence to the stringent formulation criteria for formulation qualitative (Q1) sameness and quantitative (Q2) similarity. The present study has investigated formulations and excipients from 16 putative BCS Class III drug substances in a total of 19 drug products via 133 approved abbreviated new drug applications (ANDAs) containing in vivo bioequivalence (BE) studies in human subjects during the time period from 2006 to 2022. We included the BCS Class III drugs in this study by referring to published literature, the World Health Organization (WHO) BCS Class I-IV list, FDA internal assessments, and physicochemical properties (high solubility and low permeability) of specific drug substances. Based upon all 133 approved generic formulations in this study, the highest amount of each different compendial excipient with a total of 40 is defined as its corresponding typical amount that has not shown any potential impact on in vivo drug absorption. In the present study, although only 30.08% of the investigated generic formulations met Q1 the same/Q2 similar formulation criteria for the BCS Class III biowaiver, and while approximately 69.92% failed to meet those criteria with non-Q1/Q2 similar formulations, all test/reference ratios (T/R) and 90% confidence intervals for all instrumental PK parameters (AUC0-t, AUC0-inf, and Cmax) met the bioequivalence (BE) criteria (80-125%). The results of formulation assessment suggest that the commonly used excipients without atypical amounts did not impact absorption of 16 putative BCS Class III drug substances. The rate and extent of absorption of drugs appears to be more dependent upon the biopharmaceutic and physiochemical properties of BCS Class III drug substance and less, or not dependent upon their formulations, excipients, and the excipients class. Our findings may lead to a more flexible formulation design space regarding the stringent BCS Class III formulation criteria.

Widespread neuronal and glial hyperphosphorylated tau deposition in ALS with cognitive impairment.

Although the biological basis of frontotemporal syndromes associated with amyotrophic lateral sclerosis (ALS) is considered to be altered metabolism of TDP-43, in ALS with cognitive impairment (ALSci) the metabolism of tau protein is also altered. This includes neuronal hyperphosphorylation (pThr(175)). Using novel polyclonal phospho-tau antibodies (pSer(208, 210), pThr(217) and pThr(175)) and antibodies directed against PHF tau (pSer(202)), TDP-43 or ubiquitin, we characterized tau deposition in ALS and ALSci. In ALS, we observed pThr(175) tau immunoreactive intraneuronal and neuritic aggregates throughout the amygdala and entorhinal cortex. In ALSci, this extended to the anterior cingulate gyrus, superior frontal cortex and substantia nigra. The pThr(217) antibody detected widespread astrocytic tau deposition, including punctuate or fibrillary aggregates, or intensely immunoreactive tufted astrocytes in the superior frontal cortex, anterior cingulate gyrus, entorhinal cortex, amygdala and basal ganglia of ALS. In ALSci, a similar but more widely distributed pThr(217) pathology was observed. There was no correlation between the extent of pathological tau deposition and TDP-43 pathology, although nuclear TDP-43 immunoreactivity was absent in neurons with tau pathology. In conclusion, ALSci is unique in possessing both tau and TDP-43 pathology. The presence of widespread astrocytic tau pathology suggests that ALSci may initially be characterized by astrocytic pathology.