Comparison of the Effects of Lidocaine and Amiodarone on Patients With Cardiac Arrest: A Systematic Review and Meta-Analysis.

The objective of this study was to compare the impact of amiodarone and lidocaine on survival and neurological outcomes following cardiac arrest. A systematic review of randomized controlled trials (RCTs) as well as cohort and cross-sectional trials was undertaken, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Potential relevant studies were searched in databases, including PubMed, Embase, Cochrane Library, and Web of Science, from the beginning of databases to February 15, 2024. Outcomes assessed in this study were survival to hospital discharge, survival to hospital admission or 24 hours, favorable neurological outcomes, and return of spontaneous circulation (ROSC). A total of seven studies (five observational and two RCTs) were included in this meta-analysis encompassing 19,081 patients with cardiac arrest. Pooled analysis showed no difference between amiodarone and lidocaine in terms of survival to hospital discharge (odds ratio (OR): 0.88, 95% confidence interval (CI): 0.75 to 1.04), ROSC (OR: 0.94, 95% CI: 0.84 to 1.05, p-value: 0.25), favorable neurological outcomes (OR: 0.88, 95% CI: 0.66 to 1.17, p-value: 0.38), and survival to 24 hours (OR: 0.82, 95% CI: 0.55 to 1.21, p-value: 0.31). While lidocaine demonstrated a slight survival advantage, the differences were statistically insignificant. Similarly, no significant variations were observed in ROSC incidence, neurological outcomes, or survival at 24 hours. These findings align with current guidelines but underscore the necessity for further rigorous RCTs to provide conclusive recommendations.

Assessment of land use management and its effect on soil quality and carbon stock in Ebonyi State, Southeast Nigeria.

Evaluating soil quality (SQ) resulting from land management use impact is important for soil carbon (C) monitoring, land sustainability and suitability. However, the data in less developed regions of Africa like Nigeria is scarce, limiting our understanding at global scale. The study evaluated land management use on soil quality in Ebonyi State, Nigeria, a representative region of Africa. Soil samples were collected in 2021 and resampled in 2022 from regions including five land use managements (FS = forest soil; GLS = grass land soil; ACS = alley cropping Soil; SDS = sewage dump-soils; CCS = continuously cultivated soil). Soil physical and chemical properties were analyzed and discussed. The results shows that soil physical properties (bulk density, hydraulic conductivity, aggregate stability) were significantly (P < 0.05) influenced by land use management. Moderate to high bulk density, very low hydraulic conductivity (HC), and low aggregate stability were observed across land management, suggesting potential inhibition to root penetration, poor aeration, and water infiltration. Improved land management practices such as planting of cover crops either for re-grassing or addition of crop residues could be adopted as conservative options for increasing soil quality and encourage additional soil C. Soil pH decreased with the increase in soil depth in all land uses for both years. A higher soil pH of 6.78 (slightly acidic) was seen in SDS and lower mean 6.0 (moderately acidic) was obtained in CCS at 0-20 cm in 2021. The average mean nitrogen content was rated "very high" (0.81 g kg-1 and 0.69 g kg-1) in 2021 and 2022 respectively, suggesting nitrogen might not be a limiting factor for plant growth in the region. During the 2021 and 2022 study periods, the overall average mean C stock were 12.71 g kg-1 and 15.87 g kg-1 respectively suggesting 3.1 g kg-1 C stock increment in 2022. Soil inorganic C also increased by 9.86 g cm-2 in 2022. The study provided crucial information about how land management use affected soil physico-chemical properties including C stock and suggested that C stock could be improved by adopting appropriate land management use practices. The results fill a data gap in under-studied regions, but also facilitate potential land management practices.

Methylation of softwood and hardwood kraft lignins with chloromethane.

Methylation is a well-established means of enhancing the thermal stability, improving the compatibility in polymer blends, and lowering the glass-transition temperature of lignins. This process normally involves reagents that are costly, associated with poor atom economy and/or highly toxic. Herein, we report the methylation of softwood and hardwood kraft lignins using chloromethane in alkaline aqueous media. This reaction proceeds in high yields at 90-110 °C under moderate pressure (40 psi) while generating environmentally benign sodium chloride and water as by-products.

Final analysis of phase II results with cemiplimab in metastatic basal cell carcinoma after hedgehog pathway inhibitors.

BACKGROUND: Metastatic basal cell carcinoma (mBCC) is a rare condition with no effective second-line treatment options. Cemiplimab is an immune checkpoint inhibitor that blocks the binding of programmed cell death-1 (PD-1) to its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Here, we present the final analysis of cemiplimab in patients with mBCC after first-line hedgehog pathway inhibitor (HHI) treatment (NCT03132636). PATIENTS AND METHODS: In this open-label, single-arm, phase II study, adults with mBCC and Eastern Cooperative Oncology Group performance status ≤1, post-HHI treatment, received cemiplimab 350 mg intravenously every 3 weeks for ≤93 weeks or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review (ICR). Duration of response (DOR) was a key secondary endpoint. Other secondary endpoints were ORR per investigator assessment, progression-free survival (PFS), overall survival (OS), complete response rate, safety, and tolerability. RESULTS: Fifty-four patients were enrolled: 70% were male and the median age of patients was 64 [interquartile range (IQR) 57.0-73.0] years. The median duration of follow-up was 8 months (IQR 4-21 months). The ORR per ICR was 22% [95% confidence interval (CI) 12% to 36%], with 2 complete responses and 10 partial responses. Among responders, the median time to response per ICR was 3 months (IQR 2-7 months). The estimated median DOR per ICR was not reached [95% CI 10 months-not evaluable (NE)]. The disease control rate was 63% (95% CI 49% to 76%) per ICR and 70% (95% CI 56% to 82%) per investigator assessment. The median PFS per ICR was 10 months (95% CI 4-16 months); the median OS was 50 months (95% CI 28 months-NE). The most common treatment-emergent adverse events were fatigue [23 (43%)] and diarrhoea [20 (37%)]. There were no treatment-related deaths. CONCLUSIONS: Cemiplimab demonstrated clinically meaningful antitumour activity, including durable responses, and an acceptable safety profile in patients with mBCC who had disease progression on or intolerance to HHI therapy.

Increasing the versatility of the biphenyl-fused-dioxacyclodecyne class of strained alkynes.

Biphenyl-fused-dioxacyclodecynes are a promising class of strained alkyne for use in Cu-free 'click' reactions. In this paper, a series of functionalised derivatives of this class of reagent, containing fluorescent groups, are described. Studies aimed at understanding and increasing the reactivity of the alkynes are also presented, together with an investigation of the bioconjugation of the reagents with an azide-labelled protein.

Cytosolic actin isoforms form networks with different rheological properties that indicate specific biological function.

The implications of the existence of different actins expressed in epithelial cells for network mechanics and dynamics is investigated by microrheology and confocal imaging. γ-actin predominately found in the apical cortex forms stiffer networks compared to ß-actin, which is preferentially organized in stress fibers. We attribute this to selective interactions with Mg2+-ions interconnecting the filaments' N-termini. Bundling propensity of the isoforms is different in the presence of Mg2+-ions, while crosslinkers such as α-actinin, fascin, and heavy meromyosin alter the mechanical response independent of the isoform. In the presence of myosin, ß-actin networks show a large number of small contraction foci, while γ-actin displays larger but fewer foci indicative of a stronger interaction with myosin motors. We infer that subtle changes in the amino acid sequence of actin isoforms lead to alterations of the mechanical properties on the network level with potential implications for specific biological functions.

A monomeric StayGold fluorescent protein.

StayGold is an exceptionally bright and stable fluorescent protein that is highly resistant to photobleaching. Despite favorable fluorescence properties, use of StayGold as a fluorescent tag is limited because it forms a natural dimer. Here we report the 1.6 Å structure of StayGold and generate a derivative, mStayGold, that retains the brightness and photostability of the original protein while being fully monomeric.

A 36-Year-Old Woman With an Unexpected Cause of Hypokalemia.

A 36-year-old woman complained of bilateral lower limb weakness for the last 3 days. She could move her upper limb, neck, and facial muscles and had no respiratory or swallowing difficulties. About 4 years ago, she complained of sudden weakness involving her lower limbs. Two years later, she had another episode involving only the right upper limb. In both cases, she was hypokalemic and received oral and intravenous potassium. She is a known diabetic and has polycystic ovary disease. Her blood pressure was 150/100 mm Hg, and body mass index was 29. Her serum potassium was 2 mEq/L, plasma renin 5 ng/dL, plasma aldosterone 0.63 µIU/mL, and aldosterone to plasma renin activity ratio 8. Cushing syndrome was considered a possibility. Subsequent analysis indicated a baseline cortisol level of 19.6 µg/dL at 8 Am. A screening overnight 1-mg dexamethasone suppression test (DST) showed 17 µg/dL cortisol. The low-dose DST revealed a cortisol level of 10.8 µg/dL. Adrenocorticotropin level was 196 pg/mL, and 24-hour urinary cortisol level was 1284 mg/dL. A high dose of 8-mg DST at 11 Pm to find the source of hypercortisolism performed yielded 15.9 µg/dL. Magnetic resonance imaging of the pituitary displayed a well-defined, heterogeneously enhanced mass lesion (15 × 13 × 11 mm) in the sella with mild suprasellar extension. Transsphenoidal resection and stereotactic radiosurgery were performed on the tumor with hormone replacement and glycemic control following surgery.

Mental Health Programme in India: Has the tide really turned?

Mental disorders in India form a major public health concern and the efforts to tackle these dates back to four decades, by way of the National Mental Health Programme (NMHP) and its operational arm, the District Mental Health Programme (DMHP). Although the progress of NMHP (and DMHP) was relatively slower till recently, the last 4-5 years have seen rapid strides with several initiatives, including (i) expansion of DMHPs to 90 per cent of the total districts of the country, (ii) the National Mental Health Policy and (iii) strengthening the Mental Health Legislation by way of providing explicit provisions for rights of persons with mental illnesses. Among others, factors responsible for this accelerated growth include the easily accessible digital technology as well as judicial activism. Federal and State cooperation is another notable feature of this expansion. In this review, the authors summarize the available information on the evolution of implementation and research aspects related to India's NMHP over the years and provide a case for the positive turn of events witnessed in the recent years. However, the authors caution that these are still baby steps and much more remains to be done.

Sensory cortical ensembles exhibit differential coupling to ripples in distinct hippocampal subregions.

Cortical neurons activated during recent experiences often reactivate with dorsal hippocampal CA1 ripples during subsequent rest. Less is known about cortical interactions with intermediate hippocampal CA1, whose connectivity, functions, and ripple events differ from dorsal CA1. We identified three clusters of putative excitatory neurons in mouse visual cortex that are preferentially excited together with either dorsal or intermediate CA1 ripples or suppressed before both ripples. Neurons in each cluster were evenly distributed across primary and higher visual cortices and co-active even in the absence of ripples. These ensembles exhibited similar visual responses but different coupling to thalamus and pupil-indexed arousal. We observed a consistent activity sequence preceding and predicting ripples: (1) suppression of ripple-suppressed cortical neurons, (2) thalamic silence, and (3) activation of intermediate CA1-ripple-activated cortical neurons. We propose that coordinated dynamics of these ensembles relay visual experiences to distinct hippocampal subregions for incorporation into different cognitive maps.

An Unusual Antenatal Presentation of a Mature Pericardial Teratoma Masquerading as Congenital Pulmonary Airway Malformation.

We report an antenatal presentation of a huge pericardial mature teratoma that was referred as congenital pulmonary airway malformation (CPAM) in the late third trimester of pregnancy. Initial ultrasound evaluation revealed a huge predominantly cystic lesion with mixed echogenicity in the left hemithorax. A provisional diagnosis of pleural tumor was considered in view of previous scans at 20‒28 weeks being normal and associated pleural effusion. Magnetic resonance imaging of the fetus reported the lesion to be CPAM which was supported by postnatal computed tomographic imaging done on day 2 of life. However, intraoperatively, the lesion was found to be of pericardial origin which on subsequent histopathological examination was confirmed to be mature teratoma. We recommend considering potential differential diagnosis other than CPAM, especially when the lesion is found for the first time in the late third trimester.

Detailed Morphometric Analysis on Left Coronary Artery in the Population of North-East India.

Introduction The left ventricle, the cardiac chamber responsible for blood supply to the whole of systemic vasculature, receives most of its blood supply from the left coronary arteries (LCAs). Atherosclerosis of these vessels leading to myocardial infarction is a leading cause of death. Several invasive diagnostic or therapeutic coronary interventions are available for such patients. Just like any vascular procedure, a prior comprehensive knowledge of the dimensions of these vessels and their branching pattern is essential to perform these procedures uneventfully. No previous study in the population of North-Eastern India documents the population-specific reference for morphometric values of left coronary arteries and their anatomic variations. So, this study aims to fill up this lacuna. Methods This study was conducted in the Department of Anatomy in collaboration with the Catheterization Lab, Department of Cardiology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), Shillong. Coronary angiograms (CAG) of 100 subjects - 38 females and 62 males - were obtained from the Cardiac Catheterization Lab. Coronary angiograms were studied for the normal variant anatomy and morphometry of the LCAs - the left main coronary artery (LMCA), left anterior descending (LAD), and left circumflex (LCX).  Results The mean length and luminal diameter of LMCA were found to be 9.13±3.23 mm and 4.38±0.58 mm, respectively. The mean length of LAD and LCX were 109.46±14.49 mm and 66.27±11.56 mm, respectively. Ramus intermedius was present in 32% of the subjects, whereas the remaining subjects had bifurcations of LMCA. We also found that 86% of patients had "wrap-around LAD", while in 11% of our subjects, LAD failed to reach the apex. Diagonal branches originating from LAD were single, duplicated, and multiple in 14%, 62%, and 24% respectively. The marginal branches were found to be single, double, and multiple in 20%, 51%, and 29% respectively. Conclusion This study establishes a baseline reference on morphometry of the left coronary artery specific to the population of North-East India. This study may be of assistance to radiologists and cardiologists when performing procedures on the left coronary arteries in the population of North-Eastern India, with respect to the prevalence of anatomic variations.

Aptamers: Features, Synthesis and Applications.

Aptamers have become a topic of interest among the researchers and scientists since they not only possess all of the benefits of antibodies but also possess special qualities including heat stability, low cost, and limitless uses⋅ Here we give a review about the features, applications, and challenges of aptamers and also how they are beneficial over the antibodies for biomedical applications. Their unique features make aptamers a prominent tool in therapeutics, diagnostics, biosensors and targeted drug delivery. In conclusion, aptamers represent exciting materials for a variety of applications and can be modified to improve their properties and to extend their applications in biomedical field.

Reconditioned monocytes are immunomodulatory and regulate inflammatory environment in sepsis.

Sepsis is caused by dysregulated immune response to severe infection and hyper inflammation plays a central role in worsening the disease. The immunomodulatory properties of mesenchymal stem cells (MSCs) have been evaluated as a therapeutic candidate for sepsis. Reconditioned monocytes (RM), generated from healthy human peripheral blood mononuclear cells (PBMCs) exhibit both macrophage and MSCs-like properties. RM were administered at different stages of sepsis in a mouse model. It reduced serum levels of IL6, MCP-1, IL-10, improved hypothermia, increased survival, and recovery from 0 to 66% when combined with antibiotics in the mouse model. The reduced human leucocyte antigen DR molecules expression on RM enables their co-culture with PBMCs of sepsis patients which resulted in reduced ROS production, and up-regulated TGF-ß while down-regulating IL6, IL8, and IL-10 in-vitro. RM are potentially immunomodulatory, enhance survival in sepsis mouse model and modulate inflammatory behaviour of sepsis patient's PBMCs.

Histological risk score and its role in predicting recurrence in early-stage oral squamous cell carcinomas.

Context: Oral squamous cell carcinoma (OSCC) comprises more than 90% of oral cancers and is the most common carcinoma affecting the oral cavity. Early stage T1/T2 OSCC have a heterogeneous prognosis and a significant number of patients develop loco regional recurrence (LRR) and have reduced disease free survival (DFS) with increased disease related mortality. Aims and Objectives: To assess the impact of the three parameters used in Brandwein-Gensler risk model along with lympho-vascular invasion (LVI), depth of invasion (DOI) and lymph node metastases in predicting LRR in early stage OSCC. Materials and Methods: This was a retrospective study on early stage T1/2 OSCC patients over a period of 2 years who received treatment by surgical resection and had follow-up data. LRR was assessed based on recurrence of OSCC at the initial site or in regional lymph nodes. Results: Out of 1135 OSCC cases during our study period a total of 207 cases befitted our inclusion criteria. Recurrence was noted in 113 (54.6%) cases. Univariate analysis identified LVI (P < 0.00001), DOI (P < 0.00001), nodal involvement (P < 0.00001), worst pattern of invasion (WPOI) (P < 0.00001), lymphocytic host response (LHR) (P = 0.004), perineural invasion (PNI) (P = 0.012) as strong statistically significant risk factors for LRR. Conclusion: Adequate assessment of simple parameters on routine H and E by incorporating Brandwein-Gensler histological risk scoring model at the initial presentation can help prognosticate and predict LRR and select patients for post-surgical adjuvant therapy.

ACE2 overexpression in corticotropin-releasing-hormone cells offers protection against pulmonary hypertension.

Background: Pulmonary hypertension (PH), characterized by elevated pulmonary pressure and right heart failure, is a systemic disease involving inappropriate sympathetic activation and an impaired gut-brain-lung axis. Global overexpression of angiotensin converting enzyme 2 (ACE2), a cardiopulmonary protective enzyme of the renin-angiotensin system, attenuates PH induced by chronic hypoxia. Neurons within the paraventricular nucleus of the hypothalamus (PVN) that synthesize corticotropin-releasing hormone (CRH) are activated by stressors, like hypoxia, and this activation augments sympathetic outflow to cardiovascular tissues. These data coupled with our observations that ACE2 overexpression in CRH cells (CRH-ACE2KI mice) decreases anxiety-like behavior via suppression of hypothalamic-pituitary-adrenal (HPA) axis activity by decreasing CRH synthesis, led us to hypothesize that selective ACE2 overexpression in CRH neurons would protect against hypoxia-induced PH. Methods: CRH-ACE2KI and WT male and female mice were exposed to chronic hypoxia (10%O2) or normoxia (21%O2) for 4 weeks in a ventilated chamber with continuous monitoring of oxygen and carbon dioxide concentrations (n = 7-10/group). Pulmonary hemodynamics were measured with Millar pressure catheters then tissues were collected for histological analyses. Results: Chronic hypoxia induced a significant increase (36.4%) in right ventricular (RV) systolic pressure (RVSP) in WT mice, which was not observed in CRH-ACE2KI mice. No significant differences in RVSP were observed between male and female mice in any of the groups. Conclusion: Overexpression of ACE2 in CRH cells was protective against hypoxia-induced PH. Since the majority of expression of CRH is in brain nuclei such as paraventricular nucleus of the hypothalamus (PVN) and/or central nucleus of the amygdala (CeA) these data indicate that the protective effects of ACE2 are, at least in part, centrally mediated. This contributes to the systemic nature of PH disease and that CRH neurons may play an important role in PH.

An open-source behavior controller for associative learning and memory (B-CALM).

Associative learning and memory, i.e., learning and remembering the associations between environmental stimuli, self-generated actions, and outcomes such as rewards or punishments, are critical for the well-being of animals. Hence, the neural mechanisms underlying these processes are extensively studied using behavioral tasks in laboratory animals. Traditionally, these tasks have been controlled using commercial hardware and software, which limits scalability and accessibility due to their cost. More recently, due to the revolution in microcontrollers or microcomputers, several general-purpose and open-source solutions have been advanced for controlling neuroscientific behavioral tasks. While these solutions have great strength due to their flexibility and general-purpose nature, for the same reasons, they suffer from some disadvantages including the need for considerable programming expertise, limited online visualization, or slower than optimal response latencies for any specific task. Here, to mitigate these concerns, we present an open-source behavior controller for associative learning and memory (B-CALM). B-CALM provides an integrated suite that can control a host of associative learning and memory behaviors. As proof of principle for its applicability, we show data from head-fixed mice learning Pavlovian conditioning, operant conditioning, discrimination learning, as well as a timing task and a choice task. These can be run directly from a user-friendly graphical user interface (GUI) written in MATLAB that controls many independently running Arduino Mega microcontrollers in parallel (one per behavior box). In sum, B-CALM will enable researchers to execute a wide variety of associative learning and memory tasks in a scalable, accurate, and user-friendly manner.

Generation of a transgenic mouse embryonic stem cell line overexpressing DNMT1.

DNMT1 overexpression is reported in disorders like schizophrenia, bipolar, epilepsy and multiple cancer types. Here, we used non-homologous recombination to generate R1Dnmt1WT-1, a mouse embryonic stem cell (ESC) line carrying a Dnmt1 cDNA transgene to achieve about two-fold overexpression. This ESC line showed increased transcript levels of Sox2 pluripotency marker. R1Dnmt1WT-1 embryoid bodies showed increased levels of Lefty1 (endoderm), Tbxt and Acta2 (mesoderm), and Pax6 (ectoderm) transcripts. This new line showed normal karyotype and microsatellite profiles making it useful in studying carcinogenesis and abnormal neurogenesis due to DNMT1 overexpression.

Torsion of giant occipital encephalocoele in a 2-day-old infant: emergent surgery and outcome.

INTRODUCTION: Torsion of a giant occipital encephalocele leading to necrosis is an extremely rare complication found in neonates with only two such cases reported in literature previously. Infection and ulceration of the necrosed skin may lead to meningitis or sepsis. We present here a neonate with giant occipital encephalocele showing progressive necrosis during the first day of his life. CASE REPORT: A new-born baby, delivered vaginally, with no antenatal imaging was found to have a huge mass in the occipital region, which was covered by normal pink-purplish skin. During the first day of his life, the sac started becoming ulcerated accompanied with a rapid colour change in the skin, gradually turning darker and then black. The pedicle of the encephalocele was twisted with progressive necrosis of the encephalocele. MRI showed a giant encephalocele with single vein draining into the torcula and dysplastic occipital lobe herniating into the defect. The neonate was taken up for urgent excision and repair of the encephalocele. The encephalocele was excised 'in-total' with 'figure-of-8' repair of the meninges. One year after the operation, she appears to be well-developed without any neurological problems. CONCLUSION: Necrosis may have resulted from arterial or venous compromise caused by torsion of the pedicle during delivery or after birth. The high pressure inside the sac associated with the thin skin of the encephalocele may be another predisposing factor. In view of the risk of meningitis and rupture, immediate surgery with repair with minimal blood loss is indicated.