Prefrontal microglia deficiency during adolescence disrupts adult cognitive functions and synaptic structures: A follow-up study in female mice.

The prefrontal cortex (PFC) provides executive top-down control of a variety of cognitive processes. A distinctive feature of the PFC is its protracted structural and functional maturation throughout adolescence to early adulthood, which is necessary for acquiring mature cognitive abilities. Using a mouse model of cell-specific, transient and local depletion of microglia, which is based on intracerebral injection of clodronate disodium salt (CDS) into the PFC of adolescent male mice, we recently demonstrated that microglia contribute to the functional and structural maturation of the PFC in males. Because microglia biology and cortical maturation are partly sexually dimorphic, the main objective of the present study was to examine whether microglia similarly regulate this maturational process in female mice as well. Here, we show that a single, bilateral intra-PFC injection of CDS in adolescent (6-week-old) female mice induces a local and transient depletion (70 to 80% decrease from controls) of prefrontal microglia during a restricted window of adolescence without affecting neuronal or astrocytic cell populations. This transient microglia deficiency was sufficient to disrupt PFC-associated cognitive functions and synaptic structures at adult age. Inducing transient prefrontal microglia depletion in adult female mice did not cause these deficits, demonstrating that the adult PFC, unlike the adolescent PFC, is resilient to transient microglia deficiency in terms of lasting cognitive and synaptic maladaptations. Together with our previous findings in males, the present findings suggest that microglia contribute to the maturation of the female PFC in a similar way as to the prefrontal maturation occurring in males.

Validation of cardiac output estimation using the fourth-generation FloTrac/EV1000™ system in patients undergoing robotic-assisted off-pump coronary artery bypass surgery.

The pulmonary artery catheter (PAC)-despite its invasiveness-remains the gold standard for cardiac output (CO) monitoring. The FloTrac system, a less invasive hemodynamic monitor has been developed, which estimates CO using arterial pressure waveform analysis without external calibration. Recently, an upgraded version of FloTrac system with improved algorithm to follow changes in vascular resistance was introduced into the market. The aim of this study was to assess the reliability of the CO estimated from the fourth-generation FloTrac/EV1000 system (COFT) compared to that measured with PAC using the thermodilution method (COPAC) during robotic-assisted off-pump coronary artery bypass (OPCAB) surgery. COFT and COPAC were obtained simultaneously at 4 predefined time points during robotic-assisted OPCAB: 5 min after the induction of general anesthesia (T1), after starting one-lung ventilation (T2), after capnothorax (T3), and after mini-thoracotomy was performed (T4). The agreement of data was investigated by Bland-Altman analysis. Thirty-four patients were initially enrolled. After exclusion, 32 patients and a total of 128 paired CO measurements were obtained. The overall bias was 1.46 L/min, the 95% limits of agreements were - 3.40 to 6.33 L/min, and the percentage error was 72.98%. Regression analysis of the systemic vascular resistance index (SVRI) and the bias between COPAC and COFT showed that the bias was moderately correlated with the SVRI (r2 = 0.43; p < 0.0001). Despite a software upgrade, the reliability of the fourth-generation FloTrac/EV1000™ system during robotic-assisted OPCAB to estimate CO was not acceptable, especially in patients with low SVRI.

Deficient DNA base-excision repair in the forebrain leads to a sex-specific anxiety-like phenotype in mice.

BACKGROUND: Neuropsychiatric disorders, such as schizophrenia (SZ) and autism spectrum disorder (ASD), are common, multi-factorial and multi-symptomatic disorders. Ample evidence implicates oxidative stress, deficient repair of oxidative DNA lesions and DNA damage in the development of these disorders. However, it remains unclear whether insufficient DNA repair and resulting DNA damage are causally connected to their aetiopathology, or if increased levels of DNA damage observed in patient tissues merely accumulate as a consequence of cellular dysfunction. To assess a potential causal role for deficient DNA repair in the development of these disorders, we behaviourally characterized a mouse model in which CaMKIIa-Cre-driven postnatal conditional knockout (KO) of the core base-excision repair (BER) protein XRCC1 leads to accumulation of unrepaired DNA damage in the forebrain. RESULTS: CaMKIIa-Cre expression caused specific deletion of XRCC1 in the dorsal dentate gyrus (DG), CA1 and CA2 and the amygdala and led to increased DNA damage therein. While motor coordination, cognition and social behaviour remained unchanged, XRCC1 KO in the forebrain caused increased anxiety-like behaviour in males, but not females, as assessed by the light-dark box and open field tests. Conversely, in females but not males, XRCC1 KO caused an increase in learned fear-related behaviour in a cued (Pavlovian) fear conditioning test and a contextual fear extinction test. The relative density of the GABA(A) receptor alpha 5 subunit (GABRA5) was reduced in the amygdala and the dorsal CA1 in XRCC1 KO females, whereas male XRCC1 KO animals exhibited a significant reduction of GABRA5 density in the CA3. Finally, assessment of fast-spiking, parvalbumin-positive (PV) GABAergic interneurons revealed a significant increase in the density of PV+ cells in the DG of male XRCC1 KO mice, while females remained unchanged. CONCLUSIONS: Our results suggest that accumulation of unrepaired DNA damage in the forebrain alters the GABAergic neurotransmitter system and causes behavioural deficits in relation to innate and learned anxiety in a sex-dependent manner. Moreover, the data uncover a previously unappreciated connection between BER deficiency, unrepaired DNA damage in the hippocampus and a sex-specific anxiety-like phenotype with implications for the aetiology and therapy of neuropsychiatric disorders.

Identity-Based Proxy Re-Encryption Scheme Using Fog Computing and Anonymous Key Generation.

In the fog computing architecture, a fog is a node closer to clients and responsible for responding to users' requests as well as forwarding messages to clouds. In some medical applications such as the remote healthcare, a sensor of patients will first send encrypted data of sensed information to a nearby fog such that the fog acting as a re-encryption proxy could generate a re-encrypted ciphertext designated for requested data users in the cloud. Specifically, a data user can request access to cloud ciphertexts by sending a query to the fog node that will forward this query to the corresponding data owner who preserves the right to grant or deny the permission to access his/her data. When the access request is granted, the fog node will obtain a unique re-encryption key for carrying out the re-encryption process. Although some previous concepts have been proposed to fulfill these application requirements, they either have known security flaws or incur higher computational complexity. In this work, we present an identity-based proxy re-encryption scheme on the basis of the fog computing architecture. Our identity-based mechanism uses public channels for key distribution and avoids the troublesome problem of key escrow. We also formally prove that the proposed protocol is secure in the IND-PrID-CPA notion. Furthermore, we show that our work exhibits better performance in terms of computational complexity.

An Improved ID-Based Data Storage Scheme for Fog-Enabled IoT Environments.

In a fog-enabled IoT environment, a fog node is regarded as the proxy between end users and cloud servers to reduce the latency of data transmission, so as to fulfill the requirement of more real-time applications. A data storage scheme utilizing fog computing architecture allows a user to share cloud data with other users via the assistance of fog nodes. In particular, a fog node obtaining a re-encryption key of the data owner is able to convert a cloud ciphertext into the one which is decryptable by another designated user. In such a scheme, a proxy should not learn any information about the plaintext during the transmission and re-encryption processes. In 2020, an ID-based data storage scheme utilizing anonymous key generation in fog computing was proposed by some researchers. Although their protocol is provably secure in a proof model of random oracles, we will point out that there are some security flaws inherited in their protocol. On the basis of their work, we further present an improved variant, which not only eliminates their security weaknesses, but also preserves the functionalities of anonymous key generation and user revocation mechanism. Additionally, under the Decisional Bilinear Diffie-Hellman (DBDH) assumption, we demonstrate that our enhanced construction is also provably secure in the security notion of IND-PrID-CPA.

Pre-operative proteinuria, postoperative acute kidney injury and mortality: A systematic review and meta-analysis.

OBJECTIVE: To investigate the association of pre-operative proteinuria with postoperative acute kidney injury (AKI) development as well as the requirement for a renal replacement therapy (RRT) and mortality at short-term and long-term follow-up. BACKGROUND: Postoperative AKI is associated with surgical morbidity and mortality. Pre-operative proteinuria is potentially a risk factor for postoperative AKI and mortality. However, the results in literature are conflicting. METHODS: We searched PubMed, Embase, Scopus, Web of Science and Cochrane Library from the inception through to 3 June 2020. Observational cohort studies investigating the association of pre-operative proteinuria with postoperative AKI development, requirement for RRT, and all-cause mortality at short-term and long-term follow-up were considered eligible. Using inverse variance method with a random-effects model, the pooled effect estimates and 95% confidence interval (CI) were calculated. RESULTS: Twenty-eight studies were included. Pre-operative proteinuria was associated with postoperative AKI development [odds ratio (OR) 1.74, 95% CI, 1.45 to 2.09], in-hospital RRT (OR 1.70, 95% CI, 1.25 to 2.32), requirement for RRT at long-term follow-up [hazard ratio (HR) 3.72, 95% CI, 2.03 to 6.82], and long-term all-cause mortality (hazard ratio 1.50, 95% CI, 1.30 to 1.73). In the subgroup analysis, pre-operative proteinuria was associated with increased odds of postoperative AKI in both cardiovascular (OR 1.77, 95% CI, 1.47 to 2.14) and noncardiovascular surgery (OR 1.63, 95% CI, 1.01 to 2.63). Moreover, there is a stepwise increase in OR of postoperative AKI development when the quantity of proteinuria increases from trace to 3+. CONCLUSION: Pre-operative proteinuria is significantly associated with postoperative AKI and long-term mortality. Pre-operative anaesthetic assessment should take into account the presence of proteinuria to identify high-risk patients. PROSPERO REGISTRATION: CRD42020190065.

Generation of resonant geometric modes from off-axis pumped degenerate cavity Nd:YVO4 lasers with external mode converters.

We propose a theoretical model to generate the resonant geometric modes localized on ray periodic trajectories with orbital angular momentum. Based on the numerical analysis, we realize resonant geometric modes in the off-axis pumped degenerate cavity ${\rm Nd}{:}{{\rm YVO}_4}$Nd:YVO4 lasers with an external mode converter. The experimental results reveal that laser output modes display the planar geometric modes when the off-axis displacement is sufficiently large, and the cavity length is set to satisfy the degenerate conditions. To generate the vortex beams, the planar geometric modes are transformed into circular geometric modes. Finally, the resonant geometric modes with large orbital angular momentum (OAM) can be generated from converting the circular geometric modes with an axicon lens. The experimental results are performed to approve the theoretical analyses.

An Improved Proxy Re-Encryption Scheme for IoT-Based Data Outsourcing Services in Clouds.

IoT-based data outsourcing services in clouds could be regarded as a new trend in recent years, as they could reduce the hardware and software cost for enterprises and obtain higher flexibility. To securely transfer an encrypted message in the cloud, a so-called proxy re-encryption scheme is a better alternative. In such schemes, a ciphertext designated for a data aggregation is able to be re-encrypted as one designated for another by a semi-trusted proxy without decryption. In this paper, we introduce a secure proxy re-encryption protocol for IoT-based data outsourcing services in clouds. The proposed scheme is provably secure assuming the hardness of the bilinear inverse Diffie-Hellman problem (BIDHP). In particular, our scheme is bidirectional and supports the functionality of multi-hop, which allows an uploaded ciphertext to be transformed into a different one multiple times. The ciphertext length of our method is independent of the number of involved IoT nodes. Specifically, the re-encryption process only takes one exponentiation computation which is around 54 ms when sharing the data with 100 IoT devices. For each IoT node, the decryption process only requires two exponentiation computations. When compared with a related protocol presented by Kim and Lee, the proposed one also exhibits lower computational costs.

Correction to: 4-Phenylbutyric acid protects against vasculitic peripheral neuropathy induced by ischaemia-reperfusion through attenuating endoplasmic reticulum stress.

Unfortunately, Fig. 5 was incorrectly published in the original publication. The complete corrected Fig. 5 is given below.

Resveratrol alleviates nuclear factor-κB-mediated neuroinflammation in vasculitic peripheral neuropathy induced by ischaemia-reperfusion via suppressing endoplasmic reticulum stress.

Vasculitic peripheral neuropathy (VPN) arises from an inflammatory obstruction in the blood vessels supplying peripheral nerves and subsequent ischaemic insults, which exhibits the clinical features of neuropathic pain and impaired peripheral nerve function. VPN induced by ischaemia-reperfusion (IR) has been reported to involve nuclear factor-κB (NF-κB)-mediated neuroinflammation. Recent studies have suggested that endoplasmic reticulum (ER) stress has been implicated in the development of peripheral neuropathies. Resveratrol possesses a potent anti-inflammatory capacity. We hypothesized that resveratrol may exert a protective effect against VPN through modulating the interrelated ER stress and NF-κB pathways. Male Sprague-Dawley rats were allocated into five groups: sham, sham + resveratrol 40 mg/kg (R40), IR, IR + R20 and IR + R40. VPN was induced by occluding the right femoral artery for 4 hours followed by reperfusion. Our data have shown that VPN induced by IR led to hind paw mechanical allodynia, heat hyperalgaesia, and impaired motor nerve conduction velocity (MNCV). With resveratrol intervention, the behavioural parameters were improved in a dose-dependent manner and the MNCV levels were increased as well. The molecular data revealed that VPN induced by IR significantly increased the expression of NF-κB as well as the ER stress sensor proteins, protein kinase RNA-like endoplasmic reticulum kinase, inositol-requiring enzyme 1 and activating transcription factor 6 in the sciatic nerves. More importantly, resveratrol significantly attenuated the expression of NF-κB and the ER stress sensor proteins after IR. In conclusion, resveratrol alleviates VPN induced by IR. The mechanisms may involve modulating NF-κB-mediated neuroinflammation via suppressing ER stress.

4-Phenylbutyric acid protects against vasculitic peripheral neuropathy induced by ischaemia-reperfusion through attenuating endoplasmic reticulum stress.

Vasculitic peripheral neuropathy (VPN) is characterized by acute-to-subacute onset of painful sensory and motor disturbances that result from inflammatory obliteration of nerve blood vessels and subsequent ischaemic injury. Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of various peripheral neuropathies, and 4-phenylbutyric acid (4-PBA) is a chemical chaperone that inhibits ER stress signaling. We investigated the effects of 4-PBA on neuropathic pain associated with VPN induced by ischaemia-reperfusion (IR) and its underlying mechanisms. Male Sprague-Dawley rats were allocated to one of the following groups: sham, sham + 4-PBA, IR, and IR + 4-PBA. IR was achieved by occluding the femoral artery for 4 h followed by reperfusion. The behavioral parameters were assessed, and the expression of ER stress markers and nuclear factor (NF)-κB in sciatic nerves was measured. The behavioral data confirmed that VPN induced by IR leads to hindpaw mechano-allodynia and heat hyperalgesia as well as impaired hindpaw grip strength, indicating the development of neuropathic pain and debilitating symptoms of VPN. The molecular data revealed that VPN induced by IR activated ER stress sensors and effector molecules as well as NF-κB in the sciatic nerves, indicating the involvement of ER stress and NF-κB-mediated neuroinflammation. Notably, 4-PBA significantly reduced the expression of all these markers and improved all behavioral changes induced by IR. This study demonstrated that ER stress and NF-κB-mediated neuroinflammation contribute to VPN induced by IR and that 4-PBA has protective potential against neuropathic pain associated with VPN.

Naloxone inhibits nod-like receptor protein 3 inflammasome.

BACKGROUND: Naloxone, an opioid receptor antagonist, possesses potent anti-inflammation effects. We previously confirmed the effects of naloxone on inhibiting upregulation of inflammatory cytokine interleukin-1ß (IL-1ß). Production of mature form IL-1ß is mediated by the nod-like receptor protein 3 (NLRP3) inflammasome, a multiprotein complex composed of NLRP3, and the adaptor protein apoptosis-associated speck-like protein contains a caspase recruitment domain (ASC). We elucidated whether naloxone could inhibit the activation of NLRP3 inflammasome. MATERIAL AND METHODS: To induce IL-1ß production and NLRP3 inflammasome activation, the human monocytic leukemia cell line THP-1 cells were first primed with lipopolysaccharide (LPS, 1 µg/mL) and then activated with adenosine triphosphate (ATP, 1 mM). For NLRP3 transcription, THP-1 cells were only treated with LPS priming. RESULTS: Enzyme-link immunosorbent assay data revealed that the concentration of IL-1ß in THP-1 cells treated with LPS plus ATP was significantly higher than that in THP-1 cells treated with LPS plus ATP plus naloxone (0.1 µM) (P < 0.001). Real-time quantitative reverse transcription and polymerase chain reaction data also revealed that NLRP3 mRNA concentration in THP-1 cells treated with LPS was significantly higher than that in THP-1 cells treated with LPS plus naloxone (P = 0.001). ASC speck formation, that is, ASC assembles into a large protein complex, is an indicator for NLRP3 inflammasome activation. Our data revealed that the percentage of cells containing ASC specks in THP-1 cells treated with LPS plus ATP was also significantly higher than that in THP-1 cells treated with LPS plus ATP plus naloxone (P < 0.001). CONCLUSIONS: Naloxone inhibits NLRP3 inflammasome activation.

Effects of phosphor distribution and step-index remote configuration on the performance of white light-emitting diodes.

Phosphor-converted white light-emitting diodes (pc-WLEDs) are fabricated by combining CaSi2O2N2:Eu2+ and Ca2Si5N8:Eu2+ phosphors with a blue chip. Experimental results demonstrate that placing the red phosphor layer above the yellow one (Y down/R up) yields the highest luminous efficiency, making it the preferable phosphor distribution for pc-WLEDs rather than Y up/R down. This finding suggests that the extent of overlap between the emission spectrum of short-emission-wavelength phosphors and the excitation spectrum of long-emission-wavelength phosphors and their luminous efficacy of radiation should be taken into account simultaneously when studying the optical characteristics of pc-WLEDs. Compared to common pc-WLEDs with silicone gel as the remote layer, the proposed step-index remote configuration exhibits superior luminous efficiency because of reduced total internal reflection and Fresnel loss.

Self-textured oxide structure for improved performance of 365 nm ultraviolet vertical-type light-emitting diodes.

High performance 365 nm vertical-type ultraviolet light-emitting diodes (LEDs) are demonstrated by the insertion of a self-textured oxide mask (STOM) structure using metal-organic chemical vapor deposition. The dislocation densities were reduced significantly via the STOM by the observation of the transmission electron microcopy image. Under an injection current of 20 mA, a 50% light output power enhancement was achieved, representing an enhancement of 35.4% in light extraction efficiency and injected electron efficiency of the LED with STOM in comparison to that without STOM. At 350 mA, the light output power of the STOM-LEDs was approximately 24.4% higher. Measurements of the optical and electrical properties of the LED showed that the corrugated STOM structure improved the light scattering and reflection which increased the light output, and also enhanced the current spreading to intensify radiative recombination.

Synergistic effects of TiO2 and Cu2O in UV/TiO2/zeolite-based systems on photodegradation of bisphenol A.

In this study, TiO2/zeolite (TZ)-based composite was utilized to degrade bisphenol A (BPA) under ultraviolet (UV) irradiation. The effects of the TiO2 and Cu2O doses in TZ and Cu2O/TiO2/zeolite (CTZ) on the rate of BPA removal were identified, respectively. The surface area of TZ declined as the TiO2 loading increased. The photodegradation rate (k) of BPA in the TZ and CTZ systems fitted pseudo-first-order kinetics. Under UV (365 nm) irradiation, the k values of TiO2 (20%)/zeolite (80%), TiO2 (40%)/zeolite (60%), TiO2 (60%)/zeolite (40%), and TiO2 (80%)/zeolite (20%) were 0.51, 0.55, 0.97, and 0.91 h-1, respectively. In the UV (365nm)/TiO2 (60%)/zeolite (40%) system, the k values of CTZ with 1%, 5%, 10%, 20%, and 30% Cu2O added were 1.50, 1.04, 1.15, 1.88, and 0.47h-1, respectively. The photocatalytic activity of TZ was enhanced by adding Cu2O. The optimal dosage of TiO2 in the TZ system was 60% and that of Cu20 in the CTZ system was 20%. p-Hydroxybenzaldehyde (p-HBA), p-hydroxyacetophenone (p-HAP), p-hydroxybenzoic acid (p-HBA acid) and hydroquinone (HQ) were intermediates ofBPA photodegradation in the UV/TZ system and the rates of degradation followed the order HQ > p - HBA acid > BPA > p - HAP > p - HBA.

On the security of a dynamic ID-based authentication scheme for telecare medical information systems.

Telecare medical information systems (TMISs) are increasingly popular technologies for healthcare applications. Using TMISs, physicians and caregivers can monitor the vital signs of patients remotely. Since the database of TMISs stores patients' electronic medical records (EMRs), only authorized users should be granted the access to this information for the privacy concern. To keep the user anonymity, recently, Chen et al. proposed a dynamic ID-based authentication scheme for telecare medical information system. They claimed that their scheme is more secure and robust for use in a TMIS. However, we will demonstrate that their scheme fails to satisfy the user anonymity due to the dictionary attacks. It is also possible to derive a user password in case of smart card loss attacks. Additionally, an improved scheme eliminating these weaknesses is also presented.

Effects of opioids administered via intravenous or epidural patient-controlled analgesia after caesarean section: A network meta-analysis of randomised controlled trials.

Background: Post-caesarean section analgesia is important physiologically and psychologically for both mothers and infants. Patient-controlled analgesia is a well-established method of administering opioids for postoperative pain. However, to date, no study has systematically investigated the effects of opioids administered through intravenous patient-controlled analgesia (IVPCA) or patient-controlled epidural analgesia (PCEA) in parturients who have undergone caesarean section. Methods: This systematic review and network meta-analysis aimed to evaluate the analgesic and adverse effects of opioids administered via IVPCA or PCEA in parturients who have undergone a caesarean section. PubMed, Embase, Scopus, Web of Science, and Cochrane Library were searched from inception through 02 10, 2022 for relevant records. Randomised controlled trials (RCTs) that compared opioids administered via IVPCA or PCEA and reported outcomes of interest were included. Studies were excluded if the solution for patient-controlled analgesia contained antiemetics and/or other analgesics in addition to opioids. The methodological quality of RCTs was assessed using the revised Cochrane Risk of Bias Tool. Summary data were extracted from each eligible study. The primary outcome was pain intensity, and the secondary outcomes were opioid-related adverse effects. Frequentist network meta-analyses were performed using a contrast-based random-effects model. This study is registered with PROSPERO, CRD42021254040. Findings: Twenty-three studies with 2589 parturients were included. Compared with IVPCA morphine as a reference treatment, PCEA fentanyl had better analgesic effects at 4 h (mean difference [MD] in the visual analogue scale score, -0.75; 95% confidence interval [CI] [-1.16, -0.34]) and 8 h (MD, -0.93; 95% CI [-1.57, -0.28]) and yielded lower odds of developing nausea/vomiting (odds ratio [OR], 0.27; 95% CI [0.09, 0.80]) and sedation/drowsiness (OR, 0.22; 95% CI [0.11, 0.45]). However, PCEA fentanyl may be more likely to cause pruritus than IVPCA treatments. Interpretation: Considering the analgesic efficacy; opioid-induced nausea, vomiting, and sedation; and the well-being of breastfed infants, PCEA fentanyl may be the treatment of choice for post-caesarean section analgesia. Funding: The Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (TCRD-TPE-111-27).

Secure access control using updateable attribute keys.

In the era of cloud computing, the technique of access control is vital to protect the confidentiality and integrity of cloud data. From the perspective of servers, they should only allow authenticated clients to gain the access of data. Specifically, the server will share a communication channel with the client by generating a common session key. It is thus regarded as a symmetric key for encrypting data in the current channel. An access control mechanism using attribute-based encryptions is most flexible, since the decryption privilege can be granted to the ones who have sufficient attributes. In the paper, the authors propose a secure access control consisting of the attributed-based mutual authentication and the attribute-based encryption. The most appealing property of our system is that the attribute keys associated with each user is periodically updatable. Moreover, we will also show that our system fulfills the security of fuzzy selective-ID assuming the hardness of Decisional Modified Bilinear Diffie-Hellman (DMBDH) problem.