Sex Differences in Dopamine Release in Nucleus Accumbens and Dorsal Striatum Determined by Chronic Fast Scan Cyclic Voltammetry: Effects of social housing and repeated stimulation.

We investigated sex differences in dopamine (DA) release in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) using a chronic 16-channel carbon fiber electrode and fast-scan cyclic voltammetry (FSCV). Electrical stimulation (ES; 60  Hz) induced DA release was recorded in the NAc of single or pair-housed male and female rats. When core (NAcC) and shell (NAcS) were recorded simultaneously, there was greater ES DA release in NAcC of pair-housed females compared with single females and males. Housing did not affect ES NAc DA release in males. In contrast, there was significantly more ES DA release from the DLS of female rats than male rats. This was true prior to and after treatment with methamphetamine. Furthermore, in castrated (CAST) males and ovariectomized (OVX) females, there were no sex differences in ES DA release from the DLS, demonstrating the hormone dependence of this sex difference. However, in the DLS of both intact and gonadectomized rats, DA reuptake was slower in females than in males. Finally, DA release following ES of the medial forebrain bundle at 60  Hz was studied over four weeks. ES DA release increased over time for both CAST males and OVX females, demonstrating sensitization. Using this novel 16-channel chronic FSCV electrode, we found sex differences in the effects of social housing in the NAcS, sex differences in DA release from intact rats in DLS, sex differences in DA reuptake in DLS of intake and gonadectomized rats, and we report sensitization of ES-induced DA release in DLS in vivo.Significance Statement Dopamine release is not uniform or fixed. In the nucleus accumbens, pair housing, compared with individual housing, is shown to differentially affect dopamine responsiveness to stimulation in a sex-dependent and region-specific way. There are also sex differences in stimulated dopamine release in the dorsolateral striatum of intact rats, which are not seen in gonadectomized rats, indicating the hormone dependence of this sex difference. However, reuptake of dopamine was slower in females than in males, independent of gonadal hormones. Importantly, the electrical stimulation-induced dopamine release in the dorsolateral striatum of gonadectomized rats demonstrated sensitization of dopamine release in vivo within animals for the first time. Thus, stimulated dopamine release exhibits sex-specific neuroplasticity that is modified in females by the housing conditions.

Genetic evidence for splicing-dependent structural and functional plasticity in CASK protein.

BACKGROUND: Pontocerebellar hypoplasia (PCH) may present with supratentorial phenotypes and is often accompanied by microcephaly. Damaging mutations in the X-linked gene CASK produce self-limiting microcephaly with PCH in females but are often lethal in males. CASK deficiency leads to early degeneration of cerebellar granule cells but its role in other regions of the brain remains uncertain. METHOD: We generated a conditional Cask knockout mice and deleted Cask ubiquitously after birth at different times. We examined the clinical features in several subjects with damaging mutations clustered in the central part of the CASK protein. We have performed phylogenetic analysis and RT-PCR to assess the splicing pattern within the same protein region and performed in silico structural analysis to examine the effect of splicing on the CASK's structure. RESULT: We demonstrate that deletion of murine Cask after adulthood does not affect survival but leads to cerebellar degeneration and ataxia over time. Intriguingly, damaging hemizygous CASK mutations in boys who display microcephaly and cerebral dysfunction but without PCH are known. These mutations are present in two vertebrate-specific CASK exons. These exons are subject to alternative splicing both in forebrain and hindbrain. Inclusion of these exons differentially affects the molecular structure and hence possibly the function/s of the CASK C-terminus. CONCLUSION: Loss of CASK function disproportionately affects the cerebellum. Clinical data, however, suggest that CASK may have additional vertebrate-specific function/s that play a role in the mammalian forebrain. Thus, CASK has an ancient function shared between invertebrates and vertebrates as well as novel vertebrate-specific function/s.

An analysis of keloid patient questions on Reddit.

Reddit is one of the world's leading social media platforms, fostering active community discussions on a variety of topics including keloids. The prevalence and reach of conversations on Reddit underscore the need to investigate and understand patient perspectives and gaps in knowledge. Herein, we present an in-depth analysis of questions and concerns of Reddit users on keloids, offering valuable insights into patient experiences, knowledge gaps and treatment preferences. The study presents a distinct approach by harnessing the power of social media data to understand patient perspectives, which may not be readily apparent in clinical settings. All posts on the 'Hot' page of the subreddit r/Keloids were analyzed. Questions were categorized and subcategorized to reveal common themes. A total of 644 questions from 513 posts between 26 March 2017 and 28 August 2023 were identified and analyzed. Reddit users most frequently asked questions regarding keloid management (57.5%). Other common categories included uncertainty regarding diagnosis or symptoms (15.1%), living with keloids (7.5%) and causes or triggers (6.2%). This analysis highlights critical areas of patient knowledge gaps and potential misconceptions regarding keloids. For dermatologists, understanding these patient questions is crucial. Such insights allow for patient-centric education and treatments, ensuring more effective and comprehensive care.

An Analysis of Dermatology-Related Red-Light Therapy Patient Questions on Reddit.

BACKGROUND: Reddit is one of the world's most popular social media platforms and is increasingly used as a health information resource for patients on topics such as red-light (RL) therapy. OBJECTIVE: In this article, the authors present an analysis of prevalent patient questions and concerns regarding RL therapy. METHODS: All posts on the "Hot" page of the r/redlighttherapy subreddit were analyzed and categorized. RESULTS: A total of 930 questions from 664 posts were analyzed. The most commonly asked question category was related to product recommendations or feedback (29.7%), followed by usage instructions (15.3%), safety and side effects (12.6%), and indications and efficacy (12.3%). CONCLUSION: Understanding patient concerns and questions about RL, as expressed on online platforms like Reddit, can help clinicians improve patient satisfaction, education, and clinical outcomes. The study offers an innovative approach by using social media to uncover valuable patient insights that might not be easily observable within clinical settings.

Investigating the Relationship Between Acne and Vasodilatory Medications in a Hospital-Wide Adult Population.

Acne vulgaris is a common chronic dermatological condition characterized by obstruction and inflammation of pilosebaceous units. Recent research on a different dermatologic condition has demonstrated that the use of vasodilatory medications is associated with a decreased relative risk of rosacea. This finding is significant due to the overlapping inflammatory pathways involved in rosacea and acne. Herein, a retrospective cohort study was designed to determine the correlation between vasodilator usage and the risk of developing acne within 5 years, contrasting it with thiazide diuretics, chosen as a control due to its non-vasodilatory antihypertensive mechanism and availability of data. Angiotensin-converting enzyme (ACE) inhibitors (RR, 0.775; 95% CI, 0.727-0.826; P<0.05), angiotensin receptor blockers (ARBs) (RR, 0.739; 95% CI, 0.685-0.797; P<0.05), beta-blockers (BB) (RR, 0.829; 95% CI, 0.777-0.885; P<0.05), and calcium channel blockers (CCB) usage (RR, 0.821, 95% CI, 0.773-0.873; P<0.05) were associated with a significantly lower risk of developing acne within 5 years of initiating therapy compared to thiazide diuretics. It is unclear if thiazide diuretics are more likely to cause acne within the adult population or if vasodilators are protective against the development of acne. Finding mechanisms and therapeutics that lower the risk of developing acne is of significant public health interest, and this study provides a step toward this endeavor. Further research is required to uncover the underlying mechanisms for this reduction in the development of acne.  J Drugs Dermatol. 2024;23(6):446-449.     doi:10.36849/JDD.8362.

Sunscreen Practices and Preferences of Skin of Color Patients.

Sunscreen is an essential way to protect against photodamage from ultraviolet (UV) radiation. Despite the recognized benefits of sunscreen in preventing skin damage from UV light, its use varies across different patient groups. This cross-sectional, questionnaire-based study aims to uncover the sunscreen usage patterns, preferences, and barriers among non-Hispanic White (NHW) and skin of color (SOC) individuals. Our findings demonstrate that NHW individuals are more likely to wear sunscreen daily (31% NHW vs 25% SOC) and reapply sunscreen at least once a day (76% NHW vs 45% SOC) compared with SOC individuals. SOC individuals demonstrate a willingness to use sunscreen, but they face barriers such as cost (2% NHW vs 16% SOC), lack of knowledge in finding suitable products (22% NHW vs 41% SOC), and concerns about white cast (7% NHW vs 25% SOC). SOC individuals are less likely to know the difference between mineral and chemical sunscreen (49% NHW vs 29% SOC), less likely to learn about sunscreen from dermatologists (36% NHW vs 22% SOC), and more likely to prefer sunscreen from brands owned by people of color (13% NHW vs 47% SOC).  In addition to analyzing the broader categories of NHW and SOC, subgroup analysis was conducted on specific subgroups, including Black, Asian, and Hispanic groups. Herein, we highlight differences in motivations, sunscreen preferences, sources of information, and knowledge levels about sun protection between NHW and SOC individuals. By uncovering the unique needs and challenges faced by SOC individuals, we aim to improve culturally competent patient education and promote effective sun protection practices across diverse populations. J Drugs Dermatol. 2024;23(6):456-462.     doi:10.36849/JDD.8268.

Indole clubbed 2,4-thiazolidinedione linked 1,2,3-triazole as a potent antimalarial and antibacterial agent against drug-resistant strain and molecular modeling studies.

In the face of escalating challenges of microbial resistance strains, this study describes the design and synthesis of 5-({1-[(1H-1,2,3-triazol-4-yl)methyl]-1H-indol-3-yl}methylene)thiazolidine-2,4-dione derivatives, which have demonstrated significant antimicrobial properties. Compared with the minimum inhibitory concentrations (MIC) values of ciprofloxacin on the respective strains, compounds 5a, 5d, 5g, 5l, and 5m exhibited potent antibacterial activity with MIC values ranging from 16 to 25 µM. Almost all the synthesized compounds showed lower MIC compared to standards against vancomycin-resistant enterococcus and methicillin-resistant Staphylococcus aureus strains. Additionally, the majority of the synthesized compounds demonstrated remarkable antifungal activity, against Candida albicans and Aspergillus niger, as compared to nystatin, griseofulvin, and fluconazole. Furthermore, the majority of compounds exhibited notable inhibitory effects against the Plasmodium falciparum strain, having IC50 values ranging from 1.31 to 2.79 µM as compared to standard quinine (2.71 µM). Cytotoxicity evaluation of compounds 5a-q on SHSY-5Y cells at up to 100 µg/mL showed no adverse effects. Comparison with control groups highlights their noncytotoxic characteristics. Molecular docking confirmed compound binding to target active sites, with stable protein-ligand complexes displaying drug-like molecules. Molecular dynamics simulations revealed dynamic stability and interactions. Rigorous tests and molecular modeling unveil the effectiveness of the compounds against drug-resistant microbes, providing hope for new antimicrobial compounds with potential safety.

Comprehensive Molecular Characterization of Polymorphous Adenocarcinoma, Cribriform Subtype: Identifying Novel Fusions and Fusion Partners.

Polymorphous adenocarcinoma (PAC) is a common, usually low-grade salivary gland carcinoma. While conventional PACs are most associated with PRKD1 p.E710D hotspot mutations, the cribriform subtype is often associated with gene fusions in PRKD1, PRKD2, or PRKD3. These fusions have been primarily identified by fluorescence in situ hybridization (FISH) analysis, with a minority evaluated by next-generation sequencing (NGS). Many of the reported fusions were detected by break-apart FISH probes and therefore have unknown partners or were negative by FISH altogether. In this study, we aimed to further characterize the fusions associated with PAC with NGS. Fifty-four PACs (exclusively cribriform and mixed/intermediate types to enrich the study for fusion-positive cases) were identified and subjected to NGS. Fifty-one cases were successfully sequenced, 28 of which demonstrated gene fusions involving PRKD1, PRKD2, or PRKD3. There were 10 cases with the PRKD1 p.E710D mutation. We identified a diverse group of fusion partners, including 13 novel partners, 3 of which were recurrent. The most common partners for the PRKD genes were ARID1A and ARID1B. The wide variety of involved genes is unlike in other salivary gland malignancies and warrants a broader strategy of sequencing for molecular confirmation for particularly challenging cases, as our NGS study shows.

Pediatric Gnathic Bony and Mesenchymal Tumors.

Evaluation of bone pathology within the head and neck region, particularly the gnathic bonesis is complex, demonstrating unique pathologic processes. In part, this variation is due to odontogenesis and the embryological cells that may be involved, which can contribute to disease development and histologic variability. As with any boney pathosis, the key is to have clinical correlation, particularly with radiographic imaging prior to establishing a definitive diagnosis. This review will cover those entities that have a predilection for the pediatric population, and while it is not all inclusive, it should serve as a foundation for the pathologist who is evaluating bony lesions involving the craniofacial skeleton.

Pediatric Odontogenic Tumors.

Odontogenic tumors are rare tumors of the jaws that arise from remnants of the tooth forming apparatus. Some odontogenic tumors demonstrate strong predilection for pediatric patients including the unicystic ameloblastoma, adenomatoid odontogenic tumor, ameloblastic fibroma, ameloblastic fibro-odontoma, odontoma, and primordial odontogenic tumor. In this review, we discuss the clinical, radiographic, histopathologic, and molecular characteristics of select odontogenic tumors that demonstrate pediatric predilection and review management.

Complete loss of the X-linked gene CASK causes severe cerebellar degeneration.

BACKGROUND: Heterozygous loss of X-linked genes like CASK and MeCP2 (Rett syndrome) causes developmental delay in girls, while in boys, loss of the only allele of these genes leads to epileptic encephalopathy. The mechanism for these disorders remains unknown. CASK-linked cerebellar hypoplasia is presumed to result from defects in Tbr1-reelin-mediated neuronal migration. METHOD: Here we report clinical and histopathological analyses of a deceased 2-month-old boy with a CASK-null mutation. We next generated a mouse line where CASK is completely deleted (hemizygous and homozygous) from postmigratory neurons in the cerebellum. RESULT: The CASK-null human brain was smaller in size but exhibited normal lamination without defective neuronal differentiation, migration or axonal guidance. The hypoplastic cerebellum instead displayed astrogliosis and microgliosis, which are markers for neuronal loss. We therefore hypothesise that CASK loss-induced cerebellar hypoplasia is the result of early neurodegeneration. Data from the murine model confirmed that in CASK loss, a small cerebellum results from postdevelopmental degeneration of cerebellar granule neurons. Furthermore, at least in the cerebellum, functional loss from CASK deletion is secondary to degeneration of granule cells and not due to an acute molecular functional loss of CASK. Intriguingly, female mice with heterozygous deletion of CASK in the cerebellum do not display neurodegeneration. CONCLUSION: We suggest that X-linked neurodevelopmental disorders like CASK mutation and Rett syndrome are pathologically neurodegenerative; random X-chromosome inactivation in heterozygous mutant girls, however, results in 50% of cells expressing the functional gene, resulting in a non-progressive pathology, whereas complete loss of the only allele in boys leads to unconstrained degeneration and encephalopathy.

Positional obstructive sleep apnea in patients with atrial fibrillation.

PURPOSE: Obstructive sleep apnea (OSA) is a common, potentially modifiable condition implicated in the pathogenesis of atrial fibrillation (AF). The presence and severity of OSA is largely sleep position-dependent, yet there is high variability in positional dependence among patients with OSA. We investigated the prevalence of positional OSA (POSA) and examined associated factors in patients with AF. METHODS: We recruited an equal number of patients with and without AF who underwent diagnostic polysomnography. Patients included had ≥ 120 min of total sleep time with 30 min of sleep in both supine and lateral positions. POSA was defined as an overall apnea hypopnea index (AHI) ≥ 5/h, supine AHI (sAHI) ≥ 5/h, and sAHI greater than twice the non-supine AHI. POSA prevalence was compared in patients with and without AF adjusting for age, sex, OSA severity, and heart failure. RESULTS: A total of patients (male: 56%, mean age 62 years) were included. POSA prevalence was similar between the two groups (46% vs. 39%; p = 0.33). Obesity and severe OSA (AHI ≥ 30/h) were associated with low likelihood of POSA (OR [CI] of 0.17 [0.09-0.32] and 0.28 [0.12-0.62]). In patients with AF, male sex was associated with a higher likelihood of POSA (OR [CI] of 3.16 [1.06-10.4]). CONCLUSION: POSA is common, affecting more than half of patients with AF, but the prevalence was similar in those without AF. Obesity and more severe OSA are associated with lower odds of POSA. Positional therapy should be considered in patients with mild OSA and POSA.

A self-monitoring wellbeing screening methodology for keyworkers, 'My Personal Wellbeing', using an integrative wellbeing model.

BACKGROUND: The detrimental impact of Covid-19 has led to an urgent need to support the wellbeing of UK National Health Service and care workers. This research develops an online diary to support the wellbeing of staff in public healthcare in real-time, allowing the exploration of population wellbeing and pro-active responses to issues identified. METHODS: The diary was co-produced by NHS and care stakeholders and university researchers. It was based on an integrative model monitoring mental health symptoms as well as wellbeing indicators. Diary users were encouraged to reflect on their experience confidentially, empowering them to monitor their wellbeing. The data collected was analysed using Mann-Whitney-Wilcoxon and Kruskal-Wallis statistical tests to determine any significant wellbeing trends and issues. RESULTS: A statistically significant decline in wellbeing (P < 2.2E-16), and a significant increase in symptoms (P = 1.2E-14) was observed. For example, indicators of post-traumatic stress, including, flashbacks, dissociation, and bodily symptoms (Kruskal-Wallis P = 0.00081, 0.0083, and 0.027, respectively) became significantly worse and users reported issues with sleeping (51%), levels of alertness (46%), and burnout (41%). CONCLUSIONS: The wellbeing diary indicated the value of providing ways to distinguish trends and wellbeing problems, thus, informing how staff wellbeing services can determine and respond to need with timely interventions. The results particularly emphasised the pressing need for interventions that help staff with burnout, self-compassion, and intrusive memories.

Ultraflexible and Stretchable Intrafascicular Peripheral Nerve Recording Device with Axon-Dimension, Cuff-Less Microneedle Electrode Array.

Peripheral nerve mapping tools with higher spatial resolution are needed to advance systems neuroscience, and potentially provide a closed-loop biomarker in neuromodulation applications. Two critical challenges of microscale neural interfaces are 1) how to apply them to small peripheral nerves, and 2) how to minimize chronic reactivity. A flexible microneedle nerve array (MINA) is developed, which is the first high-density penetrating electrode array made with axon-sized silicon microneedles embedded in low-modulus thin silicone. The design, fabrication, acute recording, and chronic reactivity to an implanted MINA, are presented. Distinctive units are identified in the rat peroneal nerve. The authors also demonstrate a long-term, cuff-free, and suture-free fixation manner using rose bengal as a light-activated adhesive for two time-points. The tissue response is investigated at 1-week and 6-week time-points, including two sham groups and two MINA-implanted groups. These conditions are quantified in the left vagus nerve of rats using histomorphometry. Micro computed tomography (micro-CT) is added to visualize and quantify tissue encapsulation around the implant. MINA demonstrates a reduction in encapsulation thickness over previously quantified interfascicular methods. Future challenges include techniques for precise insertion of the microneedle electrodes and demonstrating long-term recording.

Efficacy and safety of a novel mucoadhesive clobetasol patch for treatment of erosive oral lichen planus: A phase 2 randomized clinical trial.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa. Currently there is no approved treatment for OLP. We report on the efficacy and safety of a novel mucoadhesive clobetasol patch (Rivelin® -CLO) for the treatment of OLP. METHODS: Patients with confirmed OLP and measurable symptomatic ulcer(s) participated in a randomized, double-blind, placebo-controlled, multicenter clinical trial testing a novel mucoadhesive clobetasol patch (Rivelin® -CLO) in OLP across Europe, Canada, and the United States. Patients were randomized to placebo (nonmedicated), 1, 5, 20 µg Clobetasol/patch, twice daily, for 4 weeks. The primary endpoint was change in total ulcer area compared to baseline. Secondary endpoints included improvement from baseline in pain, disease activity, and quality of life. RESULTS: Data were analyzed and expressed as mean [SD]. One hundred thirty-eight patients were included in the study; 99 females and 39 males, mean age was 61.1 [11.6] years. Statistical analyses revealed that treatment with 20-µg Rivelin® -CLO patches demonstrated significant improvement with ulcer area (p = 0.047), symptom severity (p = 0.001), disease activity (p = 0.022), pain (p = 0.012), and quality of life (p = 0.003) as compared with placebo. Improvement in OLP symptoms from beginning to the end of the study was reported as very much better (best rating) in the 20-µg group (25/32) patients compared to the placebo group (11/30), (p = 0.012). Adverse events were mild/moderate. Candidiasis incidence was low (2%). CONCLUSIONS: Rivelin® -CLO patches were superior to placebo demonstrating statistically significant, clinically relevant efficacy in objective and subjective improvement and, with a favorable safety profile.

A Light-Tolerant Wireless Neural Recording IC for Motor Prediction With Near-Infrared-Based Power and Data Telemetry.

Miniaturized and wireless near-infrared (NIR) based neural recorders with optical powering and data telemetry have been introduced as a promising approach for safe long-term monitoring with the smallest physical dimension among state-of-the-art standalone recorders. However, a main challenge for the NIR based neural recording ICs is to maintain robust operation in the presence of light-induced parasitic short circuit current from junction diodes. This is especially true when the signal currents are kept small to reduce power consumption. In this work, we present a light-tolerant and low-power neural recording IC for motor prediction that can fully function in up to 300 µW/mm2 of light exposure. It achieves best-in-class power consumption of 0.57 µW at 38° C with a 4.1 NEF pseudo-resistorless amplifier, an on-chip neural feature extractor, and individual mote level gain control. Applying the 20-channel pre-recorded neural signals of a monkey, the IC predicts finger position and velocity with correlation coefficient up to 0.870 and 0.569, respectively, with individual mote level gain control enabled. In addition, wireless measurement is demonstrated through optical power and data telemetry using a custom PV/LED GaAs chip wire bonded to the proposed IC.

Service user experiences of mental health assessments: a systematic review and thematic synthesis of qualitative literature.

BACKGROUND: Successive governments have placed service users' experiences at the heart of mental health services delivery and development. However, little is known about service users' experiences of assessments and there is some evidence that assessments can cause harm. AIMS: To synthesise the qualitative literature on service users' experiences of undergoing mental health service assessments. METHODS: Literature was systematically searched, screened and extracted, following PRISMA guidelines. Several search strategies were employed, including electronic database searches, handsearching, and forward and backward citation tracking, to identify literature which contained data on service users' experiences of mental health assessments. Thematic synthesis was used to derive a set of themes underpinning these experiences. RESULTS: Of the 10,137 references screened, 47 were identified as relevant to the review. Two main themes were identified: the importance of humanising assessment processes and experiences of service user agency, with each theme containing four sub-themes. CONCLUSIONS: Findings highlight key factors determining service user experience. We identify key practice implications, contextualised within the literature on trauma-informed approaches and conclude that trauma-informed approaches may aid understanding and improvement of people's assessment experiences. Further research into the experiences of people from Black and minority ethnic communities is indicated.

Assessment of APACHE II Score to Predict ICU Outcomes of Patients with AKI: A Single-center Experience from Haryana, North India.

Background: The acute physiology and chronic health evaluation (APACHE) II severity score has shown a good calibration and discriminatory value across a range of disease processes and remains the most widely used source of prognostic information on the risk for death in patients admitted to intensive care units (ICUs). Objectives: To study APACHE II scores in patients of acute kidney injury (AKI) admitted in the ICU and to find its association with outcome. Materials and methods: One hundred patients with AKI aged 18 years or above were admitted in the ICU, department of general medicine, of a tertiary care institute in Haryana, North India, from October 2019 to September 2020, were studied. Patients who had known causes of chronic kidney disease (CKD), on maintenance hemodialysis, and those who underwent renal replacement therapy (RRT) or nephrectomy were excluded. All required investigations were performed, and data were collected. The patients were followed till discharge or in-hospital mortality. Results: The mean age of the patients was 55.92 ± 18.18 years. Male-female ratio was 1.5:1. Thirty-five percent of the admitted patients had an in-hospital mortality. Sepsis (47%) was the most common cause of AKI, and 83% of the patients had underlying comorbid conditions. The mean APACHE II score of the expired patients on admission, i.e., 24.80 ± 13.65, was found to be significantly higher compared to the mean APACHE II score (17.25 ± 10.12) of the discharged patients (p-value <0.001). APACHE II score was found to have 57.14% sensitivity, 86.15% specificity, 69% PPV, 78.9% NPV, and 76% diagnostic accuracy to predict mortality among the AKI patients. Conclusion: APACHE II scoring system has a good discrimination and calibration when applied to ICU-admitted AKI patients and is a good predictor of prognosis in them. How to cite this article: Patel P, Gupta S, Patel H, Bashar MDA. Assessment of APACHE II Score to Predict ICU Outcomes of Patients with AKI: A Single-center Experience from Haryana, North India. Indian J Crit Care Med 2022;26(3):276-281.

Cellular-scale silicon probes for high-density, precisely localized neurophysiology.

Neural implants with large numbers of electrodes have become an important tool for examining brain functions. However, these devices typically displace a large intracranial volume compared with the neurons they record. This large size limits the density of implants, provokes tissue reactions that degrade chronic performance, and impedes the ability to accurately visualize recording sites within intact circuits. Here we report next-generation silicon-based neural probes at a cellular scale (5 × 10 µm cross section), with ultra-high-density packing (as little as 66 µm between shanks) and 64 or 256 closely spaced recording sites per probe. We show that these probes can be inserted into superficial or deep brain structures and record large spikes in freely behaving rats for many weeks. Finally, we demonstrate a slice-in-place approach for the precise registration of recording sites relative to nearby neurons and anatomical features, including striatal µ-opioid receptor patches. This scalable technology provides a valuable tool for examining information processing within neural circuits and potentially for human brain-machine interfaces.NEW & NOTEWORTHY Devices with many electrodes penetrating into the brain are an important tool for investigating neural information processing, but they are typically large compared with neurons. This results in substantial damage and makes it harder to reconstruct recording locations within brain circuits. This paper presents high-channel-count silicon probes with much smaller features and a method for slicing through probe, brain, and skull all together. This allows probe tips to be directly observed relative to immunohistochemical markers.

False negative diagnostic errors with polymerase chain reaction for the detection of cryptococcal meningoencephalitis.

The accuracy of the BioFire FilmArray Meningitis/Encephalitis (ME) panel for the identification of Cryptococcus has recently been called into question. The primary objective of this study was to assess the agreement between the BioFire ME polymerase chain reaction (PCR) and other markers of cryptococcal infection. This retrospective review identified five patients with cryptococcal meningoencephalitis, 4 of whom had a negative ME panel for Cryptococcus. All five cases had positive serum cryptococcal antigens, and three of five had a positive cerebrospinal fluid (CSF) culture for Cryptococcus. The BioFire ME panel does not appear to be reliable for ruling out Cryptococcus meningoencephalitis; multiple testing methods are recommended.