Background and Purpose: Oligomeric Aβ1-42 (oAβ42) exhibits agonist-like action at human α7- and α7β2-nicotinic receptors (collectively, α7*-nAChR). Aβ1-42 and an N-terminal Aβ peptide fragment (N-Aβ fragment: Aβ1-15/16) have been shown to modulate presynaptic Ca2+ and enhance hippocampus-based synaptic plasticity via α7* nAChR. Both the N-Aβ fragment and its essential core sequence, the N-Aβcore hexapeptide (Aβ10-15), protect against Aβ-associated synapto- and neurotoxicity, also involving nAChR. Here, we investigated how oAβ42, the N-Aβ fragment and N-Aβcore regulate the functional activity of α7*-nAChRs. Experimental approach: Single-channel patch clamp recordings measured the impact of ACh, oAβ42, the N-Aβ fragment, and the N-Aβcore on the function of concatenated, human α7- and α7β2-containing nAChR expressed in nAChR-null SH-EP1 cells. Molecular dynamics simulations identified potential sites of interaction between the N-Aβ fragment and the orthosteric α7*-nAChR binding interfaces. Key Results: Relative to the effects of ACh alone, oAβ42 preferentially enhanced α7β2-nAChR open probability and open-dwell times. Co-application with the N-Aβcore neutralized these effects. Further, we demonstrate that the N-Aβ fragment alone, or in combination with ACh or oAβ42, resulted in selective enhancement of α7-nAChR single-channel open probability and open-dwell times (compared to ACh or oAβ42). Conclusions and Implications: Our findings show the functional diversity of Aβ peptides in regulating α7*-nAChR function, with implications for a wide range of nAChR-mediated functions in AD. Single-channel recordings of the differential effects of oAβ42, N-Aβ fragment and/or N-Aβcore on α7*-nAChR isoform function revealed the complexities of their interactions with α7*-nAChR, with new insights into the neuroprotective actions of these N-Aβ-derived peptides.

Early Diagnosis of Thoracic Spinal Dural Arteriovenous Fistula Using Lumbar Magnetic Resonance Imaging: A Case Report

Cesarean Section Rates in India: A Retrospective Analysis of Districts and States from 2011 to 2019

The olfactory sense is crucial for organisms, facilitating environmental recognition and inter-individual communication. Ithomiini butterflies exemplify this importance not only because they rely strongly on olfactory cues in both inter- and intra-sexual behaviours, but also because they show re-emergence of macro-glomerular complexes (MGCs). These specialized structures within the antennal lobe, lost in butterflies, but present in moths where they enable the integration of information from various types of pheromones, refining responses to specific cues. In this study we present high-quality genome assemblies for four Ithomiini species, investigating chemosensory evolution and associating expression profiles with neuroanatomical differences. We found that antennal transcriptomes across species exhibit profound divergence, indicating distinct species adaptations in environmental sensing. Noteworthy, sexual dimorphism is also characterised both in chemosensory genes and non-chemosensory genes, suggesting their relevance in behaviour. Lipid-related genes exhibit sexual dimorphism, potentially linked to pheromone production or host selection. The study broadens the understanding of antennal chemosensory adaptations in butterflies, highlighting the intricate interplay between genetic diversity, ecological specialization, and sensory perception with neuro-anatomical differences. Insights into chemosensory gene evolution, expression patterns, and potential functional implications enhance our knowledge of sensory adaptations in butterflies, laying the foundation for future investigations into the genetic drivers of behaviour, adaptation, and speciation in insects.

Wolves and other wildlife species that share habitats with humans with minor options for spatial avoidance must either tolerate frequent human encounters, which may be lethal, or allocate their activity to those periods of the day when the risk of encountering humans is smallest and the consequences least severe. This may force wolves in densely human-populated and cultivated landscapes to either become highly nocturnally active or habituate to human stimuli. Based on 6,220 camera trap images of adult wolves from eight territories in Denmark, we analyzed the extent to which diel activity patterns in a wolf population in a highly cultivated landscape with fragmented forests and extensive public access could be explained from diel variation in darkness, human activity, and prey (deer) activity. We found that diel activity correlated with all three factors simultaneously with human activity (negative) having the strongest total as well as partial effect, followed by darkness (positive) and deer activity (positive). Relative to a model that smoothed activity as a function of time of the day, the three factors accounted for 94% of the explainable diel variation in wolf activity. As most of the apparent selection for darkness could be explained by temporal human avoidance, we suggest that nocturnality (proportion of observations registered at night vs. day at equinox) is a useful proxy for investment in temporal human avoidance. In this study, wolf packs were 7.0 (95% CI: 5.0-9.7) times more active at night than at daytime, which makes Danish wolves amongst the most nocturnally active wolves reported so far. This result confirms the initial prediction that wolves with few options for spatial avoidance, invest heavily in temporal human avoidance.

The current crisis of global climate change and its consequences which are manifested in form of different environmental disasters is attributed to excessive emission and accumulation of greenhouse gases in the atmosphere, key among which is carbon dioxide. Hence, remedies are needed to mitigate against this change in climate. A mathematical model on climate change incorporating good conservation policies, enlightenment programmes and direct air capture technology as mitigation measures is formulated and analysed using the concept of optimal control theory and cost-effectiveness analysis. The objective functional is set up to minimize both the excessive concentration of carbon dioxide in the atmosphere and the total cost of implementation of each mitigation measure, as the resources available to cater for the needs of the teeming human population are limited. By formulating a Hamiltonian function and using Pontryagin’s Principle, the adjoint equations and characterisation of the optimal units were calculated. Using the optimality control system obtained, the numerical simulation was done in MATLAB using the Forward Backward Sweep algorithm of the Runge-Kutta Method. Seven different strategies of mitigation scenarios were simulated. From the results, each of these strategies has the potency to reduce the excessive concentration of carbon dioxide in the atmosphere. However, the best result was obtained using the strategy that combines all the three mitigation measures of good conservation policies, enlightenment programmes and direct air capture technology. Despite that this strategy (Strategy VII) appears the most desirable option to adopt, the cost of implementation of each strategy has to be considered since human resources are limited. Therefore, cost-effectiveness analysis techniques (Average Cost-Effectiveness Ratio and Incremental Cost-Effectiveness Ratio ) were used to arrive at the most cost-friendly strategy. From the computations involving these two ratios, both indicated good conservation policies strategy as the cheapest option to adopt in reducing the excessive concentration of carbon dioxide in the atmosphere.

1. The gut microbiota of rodents is essential for survival and adaptation, and has been shown to be susceptible to a variety of factors, ranging from environmental conditions to genetic predispositions. Nevertheless, few comparative studies have considered the contribution of species identity and geographic spatial distance to the variation in gut microbiota. 2. Here, we investigated the gut microbial communities of four wild rodent species (Rattus norvegicus, Apodemus agrarius, Cricetulus barabensis, and Tscherskia triton) at five sites in northern China’s farming-pastoral transition zone. By performing a cross-factorial comparison, we are able to test whether belonging to the same species, or instead, being in the same capture site dominates in determining gut microbiota composition. 3. Our analysis found that the Amplicon Sequence Variants (ASVs) showed a partial overlap with the species identity and the geographic capture sites, which did not reveal a ‘phylosymbiosis’ pattern. 4. The gut microbiota of these four rodent species adhered to typical mammalian characteristics, predominantly characterised by the Firmicutes and Bacteroidetes phyla. As the geographic distance between populations increased, the shared microbial taxa among conspecific populations decreased. We observed that within a relatively small geographical range, even different species exhibit convergent α-diversity due to their inhabitation within the same environmental microbial pool. In contrast, the composition and structure of the intestinal microbiota in allopatric populations of A. agrarius showed marked differences, as well as C. barabensis. Additionally, geographical environmental elements, exhibited significant correlations with diversity indices. Conversely, host-related factors had minimal influence on microbial abundance. 5. These findings illuminated that the similarity of the microbial compositions was not determined primarily by the host species, the location of the sampling explained a greater amount of variation in the microbial composition, indicating that the local environment played a crucial role in shaping the microbial composition.

More than 30% of extant shark species are classified as threatened with extinction, yet reliable population-level data is often rare, frequently due to a lack of genomic resources. Here we present a new genome-wide marker set for endangered shark species. We developed a target gene capture bait set based on the transcriptome and genome of a Lamnid shark, and tested it on 36 shark specimens, representing seven species from three orders. Illumina read mapping and calling of Single Nucleotide Polymorphisms (SNPs) showed high target recovery rates, especially in the order Lamniformes, providing several thousand detected biallelic SNPs in each species tested. Our results show this marker set can be used for SNP-calling in a broad range of shark species, enabling detailed population assessments and other ecological and evolutionary studies.

Objective: This study investigated the efficacy of the prophylactic human papillomavirus (HPV) vaccine started at 2009- 2013 in Japan. Materials and Methods: The study involved 1529 eligible women aged 16 to 39 years who visited 11 outpatient clinics for various reasons in Japan. All these patients underwent an examination of HPV genotype and a Pap test using cervical cell samples. Two hundred ninty-nine women (19.6%) received the prophylactic HPV vaccine (bivalent :quadrivalent vaccine ratio = 2:1). Of the 5062 participants in the Japanese Human Papillomavirus Disease Education and Research Survey (J-HERS 2011), which was conducted in the pre-vaccination era, 3236 eligible participants were included as controls. Results: In the present study (J-HERS 2021), highest rate for HPV vaccination (53%) was observed in 22- to 27-year-old patients. Vaccinated ones showed 49% protection against low-grade intraepithelial lesions (LSIL) and atypical squamous cells not excluding high-grade squamous intraepithelial lesions (ASCH) or worse (LSIL/ASCH+), and 100% protection against high-grade squamous intraepithelial lesions (HSIL) or worse (HSIL+). The prevalences of HPV16 and HPV18 infections also significantly decreased (HPV16; 95% and HPV18; 100%), but there were no differences in HPV6 and HPV11 infections by the vaccination. The prevalences of HPV51 and HPV59 increased with vaccination, although these changes were not confirmed in the comparative study with J-HERS 2011. Comparisons between the pre-vaccination period (J-HERS 2011) and post-vaccination period (J-HERS 2021) revealed reduction rates of 43%, 51%, 88%, and 62% were observed for HPV16, HPV18, HPV16/18, and HPV31/58 infections, respectively. Similarly, reduction rates of 62% and 71% for LSIL/ASCH+ and HSIL+, respectively. The reduction rate for LSIL/ASCH+ was 88% in 16- to 21-year-old patients, whereas the rate for HSIL+ was 87% in 28- to 33-year-old patients. C onclusion: Bivalent or quadrivalent vaccines provided 100% protection against high-grade squamous cell lesions (suggestive of CIN2 or CIN3) in young women aged < 39 years at 9 to 12 years after initiation of the first nationwide HPV vaccination program in Japan. Cross-protection against HPV31 and HPV58 is likely to occur, although some HPV type replacements are inconsistent across vaccination regimens. This demonstrates a high effectiveness of HPV vaccine. In contrast, we worry about no reduction of cervical cancer in younger generation (born in 1997-2007) who are rarely vaccinated due to long term suspension of this vaccine recommendation in Japan.

Following the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) treatment algorithm for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), patients suffering from severe uncontrolled CRSwNP are recommended to receive oral corticosteroids, (revision) sinus surgery, systemic biologicals, and/or aspirin treatment after desensitization (ATAD). Given the major differences in indications, outcomes, practical considerations, risks and costs of these key pillars of treatment, there is a growing need to define criteria for each treatment option and list the clinically relevant and major considerations for them. This EUFOREA document therefore provides an expert panel overview of the expected outcomes, specific considerations and (contra)indications of the five major treatment arms of severe uncontrolled CRSwNP: oral corticosteroids, primary and revision sinus surgery, biological treatment, and ATAD. This overview of treatment considerations is needed to allow physicians and patients to consider the different options in the context of providing optimal and personalized care for severe uncontrolled CRSwNP. In conclusion, the five major treatment options for severe uncontrolled CRSwNP have intrinsic advantages, specific indications, and considerations that are of importance to the patient, the physician, and the society. This EUFOREA statement supports the unmet need to define criteria for the indication of every treatment pillar of CRSwNP.

Genetic diversity is a fundamental component of biodiversity. Examination of global patterns of genetic diversity can help highlight mechanisms underlying species diversity, though patterns may differ across the genome. Here, we compiled 6862 observations of genetic diversity from 492 species of marine fish, assessed their associations with macroecological drivers, and tested among hypotheses for diversity gradients: the founder effect hypothesis, the kinetic energy hypothesis, and the productivity-diversity hypothesis. We found that mitochondrial genetic diversity followed geographic gradients similar to those of species diversity, being highest near the equator, particularly in the Coral Triangle, while nuclear genetic diversity did not follow clear global patterns. Despite these differences, all genetic diversity metrics were strongly correlated with chlorophyll-a concentration, while mitochondrial diversity was also positively associated with sea surface temperature. Our results provide support for the kinetic energy hypothesis, which predicts that elevated mutation rates at higher temperatures increase mitochondrial diversity, and the productivity-diversity hypothesis, which posits that resource-rich regions support larger populations with greater genetic diversity. Overall, these findings reveal how environmental variables can influence mutation rates and drift in the ocean, caution against using mitochondrial macrogenetic patterns as proxies for nuclear DNA, and aid in defining global gradients of genetic diversity.

Metastatic melanoma is a cancer for which vascularization is not a diagnostic criterion. The aim of this study was to evaluate the applicabilities of laser speckle contrast imaging (LSCI) and contrast enhanced ultrasound (CEUS) in a mouse-model. B16F10 cells were xenografted to C57BL/6 mice. Mice were treated with anti-PD1 or 0.9% NaCl and tumor volume was measured daily. CEUS and LSCI were performed weekly. No difference in tumor growth or median survival were observed between treated and no-treaated mice. No significant difference in tumor volume measurement comparing caliper and CEUS was observed. LSCI and CEUS analyses showed a decrease in tumor perfusion in both groups of mice. Although both CEUS and LSCI are useful for measuring tumor volume, LSCI appears to be more robust and effective for monitoring tumor microcirculation. Non-invasive investigations are needed to better predict tumor vascularization: CEUS and LSCI have a good applicability in a mice model.

Aim: The objective of this registry study is to assess the utilization of PGx drugs among patients with CKD Methods: This study was a retrospective study of patients affiliated to the Department of Nephrology, Aalborg University Hospital, Denmark during 2021. Patients diagnosed with CKD were divided into CKD without dialysis and CKD with dialysis. PGx prescription drugs were retrieved from the Patient Administration System. Actionable dosing guidelines (AG) for specific drug-gene pairs for CYP2D6, CYP2C9, CYP2C19 and SLCO1B1were retrieved from the PharmGKB homepage. Results: Out of 1241 individuals, 25.5% were on dialysis. The median number of medications for each patient was 9 within the non-dialysis group, and 16 within the dialysis group. Thirty-one distinct PGx drugs were prescribed. Altogether, 76.0% (943 individuals) were prescribed at least 1 PGx drugs and the prevalence of prescriptions of PGx drugs was higher the dialysis group compared to the non-dialysis group. The most frequently prescribed drugs with AG were metoprolol, pantoprazole, atorvastatin, simvastatin, warfarin. Conclusion: This study demonstrated that a substantial proportion of patients with CKD are exposed to drugs or drug combinations for which there exists actionable dosing guidelines related to PGx of CYP2D6, CYP2C19, CYP2C9, and SLCO1B1.

Dobutamine stress echocardiography (DSE) is a test recommended for diagnosing coronary artery disease (CAD), which can also assess its severity. MAPSE (M-mode-derived long axis, mitral annular plane systolic excursion) can be used to measure the longitudinal shortening of the Left Ventricle (LV) which plays a major role in the pumping function of the cardiac muscle. For detecting early abnormalities, this parameter appears to be much more sensitive than global EF. Objective: In order to determine whether Delta change MAPSE in Dobutamine stress Echocardiography predicts ischemic heart disease and whether it correlates with coronary artery disease severity in patients with ischemic heart disease. Patients and Methods: This study evaluated 60 patients between April 2020 and July 2021, 30 of whom were ischemic (ischemic group) and 30 of whom were not (normal group). The MAPSE (septal, lateral, anterior, inferior anulus) is measured at each stress echo stage and the Delta MAPSE (Peak MAPSE – rest MAPSE) is calculated. Additionally, the EF is measured using modified Simpson’s method for each stage and the Delta EF (Peak EF – rest EF) is determined. These measurements are then compared between two groups. The severity of coronary artery disease is assessed using the Gensini score (GS). Results: Our study comprised a total of 60 patients, with an average age of 59.5 ± 7.3 years. The male gender was predominant, accounting for 74% of the participants. A notable disparity was observed between the two groups in terms of their diabetic history, which was statistically significant. Specifically, 53% of the patients had diabetes, whereas only 27% of the control group had the condition (p=0.035). There was a statistically significant difference observed between the two groups in terms of Delta MAPSE (p<0.0001). The Delta MAPSE in patients was recorded as -0.54 ± 0.3, whereas in the control groups it was 0.88 ± 0.7. Additionally, a statistically significant difference was found between the two groups based on Delta EF (p=0.012). The Delta EF in patients was measured as 1.5±5.6, while in the control groups, it was 4.8±3.9. There was a significant negative correlation observed between delta MAPSE and Gensini score in the patients’ group (P= 0.0085; r = - 0.47). Conversely, a negative correlation was also observed between delta EF and Gensini score in the patients’ group, although it was not statistically significant (P= .029; r = - 0.2). Conclusion: The reduced MAPSE in dobutamine stress echocardiography (DSE) is an efficient and straightforward quantitative echocardiographic technique that can accurately anticipate both the existence and the extent of coronary artery disease (CAD).

Background Due to the high mortality rate of oral squamous cell carcinoma (OSCC), early detection of the disease is critical. Despite previous research on potential diagnostic biomarkers, there is no consensus regarding the role and validity of specific biomarkers for OSCC. Aims The purpose of this study was to explore and verify diagnostic biomarkers for OSCC. Methods and Results mRNA expression data of 57 oral tissues from OSCC patients and 22 from individuals without OSCC was analyzed using a moderated t-test to determine potential biomarkers. Statistical analysis revealed 163 differentially expressed genes between OSCC and normal tissues, 68 of which were upregulated in OSCC tissue. The 11 most significantly upregulated genes were determined to be MMP1, MMP3, MMP10, CXCL10, IL8, CXCL11, MMP12, CXCL9, GBP5, RPS4Y1, and MMP13. Conclusions This study suggests that MMPs are especially promising diagnostic biomarkers and therapeutic targets for OSCC and identifies 68 upregulated genes for further research.

The nosocomial bacterium Acinetobacter baumannii is protected from antibiotic treatment by acquiring antibiotic resistances and by forming biofilms. Cell attachment, one of the first steps in biofilm formation, is normally induced by environmental metabolites. We hypothesized that vanillic acid, the oxidized form of vanillin, a widely available metabolite with antimicrobial properties, may play a role in A. baumannii cell attachment. We first discovered that A. baumannii actively breaks down VA through the evolutionarily conserved vanABKP genes. These genes are under the control of the repressor VanR, which we show binds directly to VanR binding sites within the vanABKP genes bidirectional promoter. VA in turn counteracts VanR inhibition. We identified a VanR binding site and searched for it throughout the genome especially in pili encoding promoter genes. We found a VanR binding site in the pilus encoding csu operon promoter and showed that VanR binds specifically to it. As expected, a strain lacking VanR overproduces Csu pili and makes robust biofilms. Our study uncovers the role that VA plays in facilitating the attachment of A. baumannii cells to surfaces, a crucial step in biofilm formation. These findings provide valuable insights into a previously obscure catabolic pathway with significant clinical implications.

A document by Mahfujul Z. Haque. Click on the document to view its contents.

Case Report