bluuebunny/crossref_metadata_2025 huggingface dataset:
The Negative Symptom Inventory-Psychosis Risk (NSI-PR): Psychometric Validation of the Final 11-Item Version
Authors: Strauss Gregory P , Walker Elaine F , Carter Nathan T , Luther Lauren , Mittal Vijay A
Published: December 2024

Background and Hypotheses

The lack of psychometrically validated assessment tools designed specifically to assess negative symptoms in individuals at clinical high risk (CHR) for psychosis represents a significant barrier to the early identification and prevention of psychosis. To address this need, the Negative Symptom Inventory-Psychosis Risk (NSI-PR) was developed based on the iterative, data-driven approach recommended by the National Institute of Mental Health consensus conference on negative symptoms.

Study Design

This manuscript reports the results of the second study phase that psychometrically validates the final 11-item version of the scale in data collected across 3 sites. A total of 222 participants (144 CHR and 78 clinical help-seeking controls) completed the NSI-PR, 1 week of ecological momentary assessment (EMA), and additional convergent and discriminant validity measures.

Study Results

Structural analyses replicated the previously reported strong fit for the 5-factor (anhedonia, avolition, asociality, alogia, and blunted affect) and hierarchical structures (2 super-ordinate dimensions and 5 lower-level domains). The 5 domains and 2 dimensions generally demonstrated good internal consistency, temporal stability, and interrater reliability. Convergent validity was demonstrated in relation to the 16-item beta version of the NSI-PR, Structured Interview for Psychosis-risk Syndromes negative subscale, Global Functioning Scale social and role, and EMA measures. Discriminant validity was supported by low correlations with positive, disorganized, and general psychiatric symptoms.

Conclusions

Findings indicate the final 11-item version of the NSI-PR has sound psychometric properties. The scale, which is designed specifically for CHR individuals, is brief and appropriate for use in research and clinical contexts. Accompanying training materials have been developed to support its use in multisite trials.
Polygenic and Polyenvironment Interplay in Schizophrenia-Spectrum Disorder and Affective Psychosis; the EUGEI First Episode Study
Authors: Rodriguez Victoria , Alameda Luis , Aas Monica , Gayer-Anderson Charlotte , Trotta Giulia , Spinazzola Edoardo , Quattrone Diego , Tripoli Giada , Jongsma Hannah E , Stilo Simona , La Cascia Caterina , Ferraro Laura , La Barbera Daniele , Lasalvia Antonio , Tosato Sarah , Tarricone Ilaria , Bonora Elena , Jamain Stéphane , Selten Jean-Paul , Velthorst Eva , de Haan Lieuwe , Llorca Pierre-Michel , Arrojo Manuel , Bobes Julio , Bernardo Miguel , Arango Celso , Kirkbride James , Jones Peter B , Rutten Bart P , Richards Alexander , Sham Pak C , O’Donovan Michael , Van Os Jim , Morgan Craig , Di Forti Marta , Murray Robin M , Vassos Evangelos
Published: December 2024

Background

Multiple genetic and environmental risk factors play a role in the development of both schizophrenia-spectrum disorders and affective psychoses. How they act in combination is yet to be clarified.

Methods

We analyzed 573 first episode psychosis cases and 1005 controls, of European ancestry. Firstly, we tested whether the association of polygenic risk scores for schizophrenia, bipolar disorder, and depression (PRS-SZ, PRS-BD, and PRS-D) with schizophrenia-spectrum disorder and affective psychosis differed when participants were stratified by exposure to specific environmental factors. Secondly, regression models including each PRS and polyenvironmental measures, including migration, paternal age, childhood adversity and frequent cannabis use, were run to test potential polygenic by polyenvironment interactions.

Results

In schizophrenia-spectrum disorder vs controls comparison, PRS-SZ was the strongest genetic predictor, having a nominally larger effect in nonexposed to strong environmental factors such as frequent cannabis use (unexposed vs exposed OR 2.43 and 1.35, respectively) and childhood adversity (3.04 vs 1.74). In affective psychosis vs controls, the relative contribution of PRS-D appeared to be stronger in those exposed to environmental risk. No evidence of interaction was found between any PRS with polyenvironmental score.

Conclusions

Our study supports an independent role of genetic liability and polyenvironmental risk for psychosis, consistent with the liability threshold model. Whereas schizophrenia-spectrum disorders seem to be mostly associated with polygenic risk for schizophrenia, having an additive effect with well-replicated environmental factors, affective psychosis seems to be a product of cumulative environmental insults alongside a higher genetic liability for affective disorders.
The Causal Relationships Between Inflammatory Proteins, Brain Structure, and Psychiatric Disorders: A Two-Step Mendelian Randomization Analysis
Authors: Zhao Linlin , Tan Liwen , Liu Weiqing , Zhang Sijie , Liao Aijun , Yuan Liu , He Ying , Chen Xiaogang , Li Zongchang
Published: December 2024

Background and Hypothesis

Inflammatory proteins are implicated in psychiatric disorders, but the causality and underlying mechanisms remain unclear.

Study Design

We conducted bidirectional Mendelian randomization (MR) using genetic variants from genome-wide association studies (GWAS) for 91 inflammatory proteins (N = 14 824) and 11 psychiatric disorders (N = 9725 to 1 035 760). The primary analysis used the inverse variance weighted (IVW) method, with additional sensitivity analyses to confirm robustness. A two-step MR approach assessed whether brain imaging-derived phenotypes (IDPs) mediated the observed effects.

Study Results

Forward MR analysis found the protective effect of CD40 on schizophrenia (SCZ) (IVW OR = 0.90, P = 5.29 × 10−6) and bipolar disorder (BD) (IVW OR = 0.89, P = 5.08 × 10−6). Reverse MR demonstrated that increased genetic risk of Tourette’s syndrome (TS) was associated with reduced Fms-associated tyrosine kinase 3 ligand (Flt3L) levels (Flt3L) (Wald Ratio beta = −0.42, P = 1.99 × 10−7). The protective effect of CD40 on SCZ was partially mediated by the modulation of fractional anisotropy (FA) values in the right and left superior frontal occipital fasciculus, with mediation proportions of 9.6% (P = .025) and 11.5% (P = .023), respectively.

Conclusion

CD40 exerts an immunoprotective effect on SCZ and BD, and the effect of CD40 on SCZ was partially mediated through modulation of FA values in the superior frontal occipital fasciculus. These findings enhance comprehension of the etiology of these psychiatric conditions and underscore the promise of therapeutic strategies aimed at inflammatory proteins.
Childhood Trauma Across the Schizophrenia Spectrum: A Comparison of Schizotypal Personality Disorder and Schizophrenia
Authors: Chan Chi C , Dolgopolskaia Elen-Sarrah , Goldstein Kim E , Kowalchyk Mary , Aladin Sana , Challman Katelyn N , Ng Sabrina , Reynolds Kaitlyn , Russo Danielle , Kapil-Pair Kalpana N , Hollander Sean , Rice Timothy , Perez-Rodriguez M Mercedes , Haznedar M Mehmet , McClure Margaret M , Szeszko Philip R , Hazlett Erin A
Published: December 2024

Background

The etiology of schizophrenia involves both biological and environmental risk factors. Studying childhood trauma in disorders along the schizophrenia spectrum, including schizotypal personality disorder (SPD), can inform early risk and protective factors for psychosis. However, no study has directly compared childhood trauma between SPD and schizophrenia.

Study Design

One hundred twenty-four participants (schizophrenia/schizoaffective disorder [SZ] n = 45, SPD n = 32, and healthy controls [HCs] n = 47) matched on age and gender were assessed for different types of childhood abuse and neglect as well as clinical symptoms. Kruskal-Wallis H-tests examined group differences in childhood trauma severity and logistic regression modeled childhood trauma types that were associated with an SZ vs SPD diagnosis.

Study Results

SZ and SPD had greater severity than HC on total trauma score and all types of childhood trauma assessed (all P-values < .05). SZ and SPD only differed on childhood sexual abuse, which was greater in SZ (P = .039). Childhood sexual abuse (odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.02-1.27, P = .02) and emotional abuse (OR = 0.82, 95% CI = 0.71-0.95, P = .01) were independent predictors of an SZ vs SPD diagnosis. Sensitivity analysis indicated that a cutoff at mild sexual abuse was significant in predicting SZ vs SPD when compared with none/minimal sexual abuse. In SZ, greater sexual abuse was associated with positive schizotypal traits and in SPD, greater emotional abuse was associated with depressive symptoms.

Conclusions

Findings suggest that childhood sexual and emotional abuse may be important factors that influence illness trajectory across the severity of disorders on schizophrenia spectrum. These findings have implications for understanding disease mechanisms and early prevention.
Working as a Wet Nurse: Was It More Than Just an Extra Income? A Case Study in Nineteenth-Century Rural Spain
Authors: Marco-Gracia Francisco J
Published: December 2024

One of the largest groups of workers in hospitals historically has been external wet nurses. They are responsible for raising abandoned children during their early years of life. However, we know little about them, only what the records of foundling homes tell us. In this article, we have combined information from the foundling hospital in the city of Zaragoza, Spain, with parish records of all wet nurses from 16 rural municipalities in the province throughout the nineteenth century (170 women who took care of 215 foundlings). From the data, we have studied their family profile, reproductive success, and motivations for volunteering as wet nurses. Did they only do it for the necessary extra income? Our results indicate that wet nurses had greater reproductive success than their contemporaries, using the care of foundlings as a means to space out their own marital fertility.
Determining effective dietary and ruminal fermentation parameters on live weight gain in diets formulated with selected agro-industrial by-products and their validation in performance fattening lambs
Authors: Vaghar Seyedin Seyed Morteza , Mojtahedi Mohsen , Younesi Hossein Naeimipour , Vargas-Bello-Pérez Einar
Published: December 2024

The objective of this study was to determine the effects of dietary agro-industrial by-products (AIBP) with different amounts of metabolizable energy (ME) and crude protein (CP) on fermentation (96 h) and gas production (GP) kinetics in vitro, as well as acceptability, animal performance, digestibility, and blood parameters in lambs. The gas production technique (GPT) and fermentation characteristics were used in an in vitro trial. This experiment used diets with ME contents of 6.28, 7.53, and 9.62 MJ/kg, as well as levels 120, 140, and 160 g/kg CP. Principal component analysis (PCA) was used to select the most important dietary ingredient ruminal fermentation parameters. The in vitro results showed that increasing ME and CP content increased and decreased GP (P < 0.05), respectively. An increase in CP content caused an increase in ruminal ammonia nitrogen (NH3-N) concentration (P < 0.05) and an increase in ME caused a decrease in pH (P < 0.05). PCA, by reducing the dimensions of the variables, shows that neutral detergent fiber (NDF), synchronization index (SI), and lignin as dietary parameters and pH and NH3 as fermentation quality parameters were the main variables in predicting LWG (P < 0.05). Next, to prove the ineffectiveness of dietary protein content on LWG, the highest ME content (ME = 9.62 MJ/kg) was selected for in vivo experiment. For the in vivo trial, eighteen male lambs of 6-7 months of age and 30.6 ± 2.27 kg body weight were randomly fed on three diets containing 120, 140, and 160 g/kg CP and ME 9.62 MJ/kg. There was no effect of the experimental diets on acceptability, performance characteristics, or apparent digestibility in an in vivo trial (P > 0.05). NH3-N concentration was affected by the varying content of CP (P < 0.05). The results of this study indicate that Khorasan Kurdish lambs have a high potential for using AIBP in their diet. Additionally, lamb producers can prevent N wastage without worrying about the loss of animal performance by using 120 g/kg CP, which meets the animals’ needs and has beneficial environmental consequences.
In vitro effect of vitaminB12 on embyro growth by induction of hypoxia in culture
Authors: Patat Dilara , Nisari Mehtap , Ulger Harun , Ertekin Tolga , Dagli Ertugrul , Cayan Dicle , Al Ozge , Guler Hatice , Sengul Goksemin Fatma , Tastan Mustafa
Published: December 2024

In this study, effects of vitaminB12 on embryonic development have been investigated by supplying vitaminB12 on a hypoxia-induced embryo culture. 9.5-day-old embryos from Wistar albino adult pregnant rats were used in our experimental set up.10 μM and 100 μM vitaminB12 were added to culture medium which is then exposed to in vitro hypoxia. Additionally, 11.5-day-old embryos and yolksacs were examined morphologically. Different vitaminB12 doses are compared within experimental groups. It was found that both control and experimental groups in 11.5-day-old embryos are at same developmental stage. It was also determined that oxygen deficiency influenced embryonic development and yolk sac vascularity in hypoxia group, are lagging behind in all experimental groups (P < 0.05). However, the development of vitaminB12 embryos were similar to control group under normoxic conditions (P > 0.05). It was also observed that development was compensated through supplement of vitaminB12 to hypoxia group (P < 0.05). It was indicated that the development in H + 100 μM vitB12 groups was quite close to control group. However, development of H + 10 μM vitB12 embryos were in parallel with hypoxic group. Furthermore, H + 100 μM vitB12 group showed higher embryonic development than H + 10 μM vitB12 group (P < 0.05).VitaminB12 treatment has been used to prevent intrauterine growth restriction which can be caused by many different pharmacological agents. However, nobody has investigated effects of vitaminB12 on hypoxia-induced early embryo growth retardation. In the light of our findings, administration of 100 μM vitaminB12 restores damage of embryonic development due to hypoxia and this application also increases embryonic vascularity and circulation. Thus, supplementation of vitaminB12 can be offered as a therapeutic approach towards cell death and diseases such as neurovascular and cardiovascular diseases and in the near future.
Impact of exposure to a mixture of organophosphate esters on the adrenal glands of Sprague Dawley rats
Authors: Li Zixuan , Hales Barbara F , Robaire Bernard
Published: December 2024

There is growing evidence that organophosphate esters (OPEs) can act as endocrine-disrupting chemicals. However, only a few studies have assessed the effects of OPE exposure on one of the most important endocrine glands in the body, the adrenal gland. Our aim was to test the effects of a mixture of OPEs detected in Canadian house dust on adrenal function in Sprague Dawley rats. Adult male and female rats (n = 15 per treatment group) were administered either a vehicle or an OPE mixture (0.048, 1.6, or 48 mg/kg bw/d) for 70 to 72 d via their diet. With OPE exposure, adrenal glands from male adult rats were reduced in weight, whereas those of female rats showed an increase in weight. This led us to investigate whether OPEs induce sex-specific effects on adrenal gland function and the mechanisms involved. Serum levels of two adrenal hormones, aldosterone and corticosterone, were decreased only in male serum samples. Serum levels of renin and adrenocorticotropic hormone, which regulate aldosterone and corticosterone synthesis, respectively, were assessed. Exposure to the OPE mixture decreased renin levels only in males. Serum biochemistry analysis revealed that triglycerides and LDL cholesterol levels were increased in males. Transcriptomic analysis revealed that the top affected pathways in male adrenal glands from all three treatment groups were related to potassium channels, which play a role in regulating aldosterone and corticosterone levels. The most affected pathways in female adrenal glands were related to cholesterol biosynthesis and immune functions. These results show that an environmentally relevant mixture of OPEs affects adrenal function and that these effects are sex specific.
PFKFB3 protein in adipose tissue contributes to whole body glucose homeostasis
Authors: Griesel Beth A. , Olson Ann Louise
Published: December 2024

Age‐dependent changes in adipose tissue are thought to play a role in development of insulin resistance. A major age‐dependent change in adipose tissue is the downregulation of key proteins involved in carbohydrate metabolism. In the current study, we investigate the role of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase 3 (PFKFB3) a key governor of the rate of glycolysis in adipocytes via the synthesis of fructose‐2,6‐bisphosphate that was significantly downregulated in aged mice. We employed an adipocyte‐specific PFKFB3 mouse line to investigate the role of PFKFB3 on adipocyte function. In both aged mice and PFKFB3‐knockout mice, we observed an increase in O‐glcNAcylated proteins consistent with a shift in glucose metabolism toward the hexosamine biosynthetic pathway. Under chow‐fed conditions, PFKFB3 knockout resulted in significantly smaller adipocyte area, but no difference in total fat mass. While glucose tolerance was unchanged under chow conditions, when mice were challenged with a 4 weeks high‐fat feeding, PFKFB3 deletion led to a greater decrease in glucose tolerance as well as a significant increase in macrophage infiltration. These results indicate that perturbation of the glycolytic pathway in adipose tissue has multiple effects of adipocyte biology and may play a significant role in metabolic changes associated with aging. Results of this student support the notion that changes in glucose metabolism in adipose tissue impact whole‐body metabolism.
Genetic and epigenetic factors shape phenotypes and outcomes in systemic lupus erythematosus – focus on juvenile-onset systemic lupus erythematosus
Authors: Charras Amandine , Hiraki Linda T. , Lewandowski Laura , Hedrich Christian M.
Published: December 2024

Purpose of review

Systemic lupus erythematosus (SLE) is a severe autoimmune/inflammatory disease. Patients with juvenile disease-onset and those of non-European ancestry are most severely affected. While the exact pathophysiology remains unknown, common and rare gene variants in the context of environmental exposure and epigenetic alterations are involved. This manuscript summarizes the current understanding of genetic and epigenetic contributors to SLE risk, manifestations and outcomes.

Recent findings

Though SLE is a mechanistically complex disease, we are beginning to understand the impact of rare and common gene variants on disease expression and associated outcomes. Recent trans-ancestral and multigenerational studies suggest that differential genetic and environmental impacts shape phenotypic variability between age-groups and ancestries. High genetic burden associates with young age at disease-onset, organ involvement, and severity. Additional epigenetic impact contributes to disease-onset and severity, including SLE-phenotypes caused by rare single gene variants. Studies aiming to identify predictors of organ involvement and disease outcomes promise future patient stratification towards individualized treatment and care.

An improved understanding of genetic variation and epigenetic marks explain phenotypic differences between age-groups and ancestries, promising their future exploitation for diagnostic, prognostic and therapeutic considerations.
Chatbots in Limb Lengthening and Reconstruction Surgery: How Accurate Are the Responses?
Authors: Bafor Anirejuoritse , Strub Daryn , Kold Søren , Iobst Christopher A. , Tulchin-Francis Kirsten
Published: December 2024

Background:

Artificial intelligence-based language model chatbots are being increasingly used as a quick reference for healthcare related information. In pediatric orthopaedics, studies have shown that a significant percentage of parents use online search engines to find out more about the health condition of their children. Several studies have investigated the accuracy of the responses generated from these chatbots. The accuracy of responses with these programs in limb lengthening and reconstruction surgery has not previously been determined. Our goal was to assess the response accuracy of 3 different chatbots (ChatGPT, Google Bard, and Microsoft Copilot) to questions related to limb reconstruction surgery.

Methods:

A list of 23 common questions related to limb reconstruction surgery was generated and posed to the 3 chatbots on 3 separate occasions. Responses were randomized and platform-blinded before rating by 3 orthopaedic surgeons. The 4-point rating system reported by Mika et al was used to grade all responses.

Results:

We found that ChatGPT had the best response accuracy score of all 3 chatbots while Microsoft Copilot had the worst score, and this finding was consistent among all 3 raters.

Conclusions:

Using the Response Accuracy Score, the responses from ChatGPT were determined to be satisfactory, requiring minimal clarification, while responses from Microsoft Copilot required moderate clarification.

Level of Evidence:

Level IV—diagnostic.
Efficacy and Safety of Probiotics as Adjunctive Therapy in Cancer Treatment
Authors: Qureshi Zaheer , Jamil Abdur , Altaf Faryal , Siddique Rimsha
Published: December 2024

Objectives:

The gut microbiome is crucial in influencing cancer progression and response to treatment. We evaluate the efficacy and safety of probiotics and synbiotics in cancer treatment, focusing on the incidence of diarrhea, significant complications, surgical site infections, length of hospital stay, progression-free survival (PFS), and overall survival (OS).

Methods:

Following PRISMA guidelines, a comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and Cochrane CENTRAL up to June 2024. The risk of bias was assessed using the Cochrane Risk-of-Bias tool. Meta-analysis was performed using a random-effects model.

Results:

Fifteen studies involving 2197 participants were included. Probiotic use was associated with a significant reduction in the incidence of diarrhea (OR=0.39, 95% CI: 0.15-1.00, P=0.049) with moderate heterogeneity (I
2=64%). No significant differences were found in major complications (OR=0.50, 95% CI: 0.05-4.92, P=0.4053, I
2=73%), surgical site infections (OR=0.36, 95% CI: 0.12-1.09, P=0.058, I
2=0%), length of hospital stay (SMD=−0.30, 95% CI: -1.00 to 0.41, P=0.2726, I
2=62%), PFS (HR=0.61, 95% CI: 0.03-10.82, P=0.2715, I
2=0%), or OS (HR=0.52, 95% CI: 0.00-58.82, P=0.3298, I
2=0%).

Conclusions:

Probiotics significantly reduced the incidence of chemotherapy-induced diarrhea, highlighting their potential as supportive care agents in oncology. However, their impact on significant complications, surgical site infections, length of hospital stay, and survival outcomes remains inconclusive.
A Rare Case With a Review of Cutaneous Composite Hemangioendothelioma and the Role of Neuroendocrine Markers
Authors: Sahu Ajit , Ayyanar Pavithra , Aparnna J.N. , Gunasekar Sudhakar , Mishra Pritinanda
Published: December 2024

Composite hemangioendothelioma comprises permutations of different histological patterns few of which have been found to have specific genetic alteration and immunohistochemical expression. It comprises retiform or epithelioid hemangioendothelioma-like areas, with a variable proportion of hemangioma or low-grade angiosarcoma-like areas. It was found to express neuroendocrine markers and was seen to have a worse prognosis in recurrence or distant metastasis. A 29-year-old woman presented with a lesion of 22 cm in size in her right leg. Biopsy and wide local excision showed features of composite hemangioendothelioma. This is a recurrent lesion after initial resection 2 years back, along with a cutaneous metastasis in the thigh. We report this rare case with a literature review, highlighting the importance of uncommon histomorphology and neuroendocrine marker expression in predicting local recurrence and cutaneous metastasis.
Postautologous Hematopoietic Stem Cell Transplantation Disseminated Hypopigmented Keratosis
Authors: Sripodok Supasan , Wu Nan-Lin , Wu Yu-Hung
Published: December 2024

Disseminated hypopigmented keratosis is a rare distinct clinical entity. This report describes the case of a 19-year-old male patient who developed disseminated hypopigmented keratosis 2 months after autologous hematopoietic stem cell transplantation for pineal choriocarcinoma. The patient displayed numerous tiny whitish or depigmented macules and papules on the chest, back, posterior neck, shoulders, arms, and thighs, closely resembling lichen nitidus. Microscopically, the lesion was orthokeratotic, acanthotic, and flat-bottomed without cytological atypia. Dermal inflammation was minimal. Fontana–Masson, Melan-A, and sex-determining region Y-box transcription factor 10 staining revealed a significant decrease in both basal melanin content and the number of melanocytes. The patient was initially administered a topical agent comprising hydrocortisone and urea, which exhibited minimal improvement. This case report suggests that disseminated hypopigmented keratosis may be a rare cutaneous manifestation of autologous hematopoietic stem cell transplantation. Additional research is necessary to gain a more comprehensive understanding of the pathogenesis and the clinical course of this disease.
Age is associated with altered locomotor and hypothermic response to acute nicotine
Authors: Novoa Carlos , Garcia-Trevizo Prescilla , Gould Thomas J.
Published: December 2024

Cigarette smoking is at an all-time low. However, nicotine consumption has diversified with the introduction of commercial tobacco products that include Electronic Nicotine Delivery Systems. Nicotine is the main psychoactive component of tobacco and contributes to the addictive properties of tobacco products. Prolonged nicotine exposure induces neural adaptations that promote addiction-related behaviors in an age-dependent manner. Here, we investigated nicotine sensitivity among young adult and middle-aged male mice by comparing initial responses to nicotine tartrate from different suppliers. We observed that all nicotine compounds tested in the present study induced a robust reduction in locomotor activity and body temperature, and nicotine exposure resulted in increased serum cotinine concentration. We observed age-related differences in the magnitude and the time course of nicotine responses for locomotor and hypothermic effects. Reduction in locomotor activity was larger among young adult mice, but the time course of this response was similar for both age groups. Nicotine-induced reduction in body temperature was of a comparable magnitude for both age groups but young adults showed a faster decrease than middle-aged mice. These results suggest that age of exposure is a key factor contributing to nicotine sensitivity and its potential addictive effects. These responses were consistently produced for nicotine tartrate from different sources. Our findings reveal distinct responses between young adults and middle-aged mice, suggesting that age-specific neurobiological mechanisms in nicotine sensitivity continue developing into adulthood. These age-related variations in nicotine response are crucial for developing targeted interventions and understanding the risk factors for nicotine dependence across the lifespan.
1,4-dihydroxy-2-naphthoic acid prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced motor function deficits
Authors: Madison Caitlin A. , Debler Roanna A. , Gallegos Paula L. , Hillbrick Lauren , Chapkin Robert S. , Safe Stephen , Eitan Shoshana
Published: December 2024

Parkinson’s disease (PD), characterized by death of dopaminergic neurons in the substantia nigra, is the second most prevalent progressive neurodegenerative disease. However, the etiology of PD is largely elusive. This study employed the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rodent model to examine the effectiveness of 1,4-dihydroxy-2-naphthoic acid (1,4-DHNA), an aryl hydrocarbon receptor (AhR) active gut bacteria-derived metabolite, in mitigating MPTP’s motoric deficits, and the role of AhR in mediating these effects. Male C57BL/6 mice were fed daily with vehicle, 20 mg/kg 1,4-DHNA, or AhR-inactive isomer 3,7-DHNA, for 3 weeks before administration of 80 mg/kg MPTP or vehicle. Four weeks later, mice were assessed for motoric functions. Both 1,4-DHNA and 3,7-DHNA prevented MPTP-induced deficits in the motor pole test and in the adhesive strip removal test. Additionally, 1,4-DHNA improved balance beam performance and completely prevented MPTP-induced reduction in stride length. In contrast, 3,7-DHNA, an AhR-inactive compound, did not improve balance beam performance and had only a partial effect on stride length. This study suggests that natural metabolites of gut microbiota, such as 1,4-DHNA, could be beneficial to counteract the development of motor deficits observed in PD. Thus, this study further supports the hypothesis that pathological and mitigating processes in the gut could play an essential role in PD development. Moreover, this indicates that 1,4-DHNA’s ability to combat various motor deficits is likely mediated via multiple underlying molecular mechanisms. Specifically, AhR is involved, at least partially, in control of gait and bradykinesia, but it likely does not mediate the effects on fine motor skills.
Repeatability of Posterior Corneal Surface Measurements and Zernike Polynomials of Two Ocular Biometers With Single and Dual Scheimpflug Cameras in Keratoconus and Healthy Eyes
Authors: Bucur Julian , Kaiser Klemens Paul , Biller Marvin Lucas , Kohnen Thomas , Lwowski Christoph Martin
Published: December 2024

Purpose:

This study aims to evaluate the repeatability of posterior corneal surface and Zernike polynomial measurements of 2 different ocular biometers and Scheimpflug devices in keratoconus (KC) and healthy eyes.

Methods:

This is a prospective, comparative study performed at the Department of Ophthalmology, Goethe-University Frankfurt, Germany. Included were KC and healthy eyes. Two consecutive measurements of 1 eye per patient, taken with Galilei G6 (Ziemer, Switzerland) and Pentacam AXL (Oculus, Germany), were analyzed. Repeatability was evaluated for posterior keratometry (K1, K2 and Km), posterior astigmatism, and the following Zernike polynomials: Defocus, Astigmatism, Coma, Trefoil, Spherical Aberration, and root mean square (RMS) total.

Results:

Both devices showed good repeatability for many of the analyzed parameters with several interclass correlation (ICC) values of 0.96 or above. Regarding the Zernike polynomials, ICC values and the narrowness of the 95% limits of agreement varied in between the devices for each polynomial. In addition, the agreement between both devices was reduced for the Zernike analysis. The only comparable polynomials were Spherical Aberration with a high interdevice ICC of 0.955 and RMS total with a lower ICC of 0.591 (both in the KC group).

Conclusions:

Regarding the posterior measurements, Pentacam AXL showed higher repeatability in healthy eyes and Galilei G6 in KC eyes. For both devices, the intradevice repeatability was high for most Zernike polynomials. However, the interdevice comparability for Zernike polynomials was reduced to Spherical Aberration and RMS total, with Spherical Aberration showing higher agreement in KC eyes.
Genomic characteristics of a Streptococcus suis of ST353 resulting in severe endophthalmitis with bilateral deafness
Authors: Shen Liang , Tong Yanfei , Li Shichao , Chen Yuda , A Ruhan , Li Zhen , Wang Wenling , Yin Lijuan , Zou Jiuming , Sun Ziyong , Wu Changcheng , Tan Wenjie
Published: December 2024

Background:

Streptococcus suis (S. suis) can be transmitted to humans through exposure to pigs or consumption of raw pork and causes serious diseases. Although infection through skin abrasions is considered an important route of transmission, few studies have reported skin injuries in patients during exposure or before infection. This study explored a rare instance of intraocular infection and bilateral deafness caused by S. suis and emphasized the importance of timely diagnosis and treatment to prevent disease progression.

Methods:

The diagnosis was made on the basis of clinical symptoms, imaging, molecular detection, and isolated culture methods. Drug susceptibility testing was conducted to determine the effectiveness of antibiotics. Whole-genome sequencing was used to identify the strain’s sequence type and serotype as well as the presence of pathogenicity islands (PAIs).

Results:

A patient with intraocular infection and bilateral deafness was diagnosed with an S. suis infection. The infection was hypothesized to result from interspecies transmission due to the patient’s occupation and recent skin damage. The isolated strain was sensitive to ampicillin, ceftriaxone, vancomycin, linezolid, levofloxacin, and meropenem. Whole-genome sequencing revealed that the strain belonged to sequence type 353 and serotype 2, showing close similarity to strains isolated from wild boars in Chinese provinces. The strain lacked the 89 complete kb PAI but had a 33 kb PAI with high similarity, potentially indicating variable virulence.

Conclusion:

This study highlights the importance of employing multiple diagnostic strategies for the timely identification and treatment of S. suis infections. The presence of a potentially less virulent strain emphasizes the need for continuous surveillance and monitoring of emerging S. suis infections, particularly in Asian countries with high-risk populations associated with the pig farming industry.
Glaucoma Progression in Treatment-Naïve Patients With Normal Tension Glaucoma With Myopia—Role of Intraocular Pressure
Authors: Han Dong Kyun , Lee Eun Ji , Kim Tae-Woo
Published: December 2024

Précis:

While myopia has been recognized as a positive prognostic factor for normal tension glaucoma (NTG) progression in the adult population, some myopic NTG eyes exhibited significant progression within 2 years when left untreated, even under low intraocular pressure (IOP).

Objective:

To determine the natural history and risk factors associated with progressive retinal nerve fiber layer (RNFL) thinning in previously stable, treatment-naïve, patients with NTG with myopia.

Methods:

This study included 111 myopic NTG eyes without IOP-lowering treatment for at least 1 year and without disease progression during the treatment-free period. The RNFL thickness was measured, and a visual field test was performed every 6–12 months for >2 years. Patients with progressive changes were classified as the P(+) group, whereas those without progression were classified as the P(–) group. Cox proportional hazards model assessed risk factors of progression, whereas linear regression determined factors associated with the rate of RNFL thinning.

Results:

Progressive change was observed in 25 of the 111 participants [P(+) group, 22.5%]. A family history of glaucoma, higher mean IOP, and maximum IOP during the follow-up were significant factors both for being in the P(+) group and for a faster RNFL thinning. None with a mean IOP <11 mm Hg were in the P(+) group. Davies test identified that 14.2 mm Hg was a significant breakpoint (P = 0.042), above which the rate of RNFL thinning increased significantly with the mean IOP (R
2 = 0.252, P = 0.034).

Conclusions:

Patients with myopic NTG untreated for IOP, especially those with a family history of glaucoma or higher IOP, are at increased risk of progression. Early treatment initiation is advised for high-risk patients with myopic NTG, even when their condition appears stable.
Association Between Metabolic Syndrome and Physical Fitness in Firefighters in Cape Town, South Africa
Authors: Ras Jaron , Grace Jeanne
Published: December 2024

Objective

To assess the relationship between metabolic syndrome (MetS) and physical fitness in firefighters.

Methods

Firefighters (n = 309) were systematically recruited to participate in this study. A questionnaire and physical measures were used to collect data on firefighters’ cardiometabolic health and physical fitness levels. Data were analyzed using binary and multinomial logistic regressions.

Results

The prevalence of MetS was 23.0%, which was most prevalent in station and platoon commanders. Multivariable analysis showed that age (P < 0.001), lean body mass (P < 0.001), absolute aerobic capacity (P < 0.001), and leg strength (P < 0.001) was significantly associated with MetS. In addition, relative aerobic capacity (P < 0.001), push-ups (P = 0.016), and sit-ups (P < 0.001) were inversely associated with MetS.

Conclusions

Firefighters with MetS had a higher absolute aerobic capacity and strength, and healthier fighters had a higher relative aerobic capacity, muscular endurance capacity, and flexibility.
Ultrasound-guided Percutaneous Fine-needle Aspiration Performed by In-training Pulmonologist
Authors: Perez-Gutierrez Victor , Khalid Amnah , Camere Maurizio , Perwaiz Muhammad
Published: December 2024

Ultrasound (US)-guided fine-needle aspiration (FNA) is a minimally invasive procedure that can be performed by an in-training pulmonologist. This is a retrospective study of 73 patients who underwent US-guided FNA by pulmonologist and interventional radiologist. Comparable diagnostic yield was found in this study (88.0% vs 81.3%, P = 0.460), but a higher number of second diagnostic procedures was seen in the Interventional Radiology group (22.9% vs 16.0%, P = 0.488). No significant complications were reported in the pulmonary group. In-training pulmonologists can safely perform US-guided FNA for thoracic and extrathoracic lesions.
The determination of euglobulin clot lysis time reference intervals in Beckton Dickinson and Kima 3.2% sodium citrate coagulation tubes
Authors: Kuktić Ivona , Pašalić Ante , Čančarević Ognjen , Galić Edvard , Saračević Andrea , Radišić Biljak Vanja
Published: December 2024

Enhanced fibrinolysis or hyperfibrinolysis may lead to life-threatening blood loss, while reduced activity may contribute to thrombosis. Euglobulin clot lysis time (ECLT) is a manual method that measures plasma fibrinolytic activity and is considered the gold standard. However, the data on reference interval is scarce and outdated. We have employed one-sided reference interval (>3 h) since the implementation of ECLT in our laboratory; therefore, we aimed to establish reliable ECLT reference interval and to explore the possible preanalytical influence of different blood collection tubes on the established ECLT reference interval. Establishing a reference interval for fibrinolysis was performed according to CLSI EP28-A3c guidelines by employing a posteriori direct sampling technique. The predefined exclusion criteria included a history of malignant or hepatobiliary disease, a history of deep vein thrombosis/pulmonary embolism (DVT/PE), an acute inflammatory state at the time of the venipuncture. We collected vein blood samples in Vacutest plastic coagulation tubes (Kima, Italy) and Vacutainer glass coagulation tubes (Beckton Dickinson, USA) containing 0.109 mol/l buffered trisodium citrate as an anticoagulant at a blood-to-anticoagulant ratio 9 : 1. We calculated two-sided reference interval and presented as 2.5th and 97.5th percentiles. ECLT values did not differ between sexes or the types of tubes enrolled in the study (P = 0.8979). The established reference interval ranged from 130 to 297 min for the KIMA Vacutest tube and from 120 to 292 min for the BD Vacutainer tube. The established ECLT reference interval differed significantly from the currently used cut-off value in our laboratory, thus enabling the assessment of hyperfibrinolysis by employing double-sided reference interval.
Heterogeneity in Pancreatitis
Authors: Bellin Melena D. , Andersen Dana K. , Akshintala Venkata , Born Dianna , Coghill Robert C. , Easler Jeffrey , Fogel Evan L. , Forsmark Christopher E. , Freeman A. Jay , Hughes Steven J. , Jensen Amy , Liran Omer , Martin Linda , Pandol Stephen J. , Palermo Tonya M. , Papachristou Georgios I. , Park Walter G. , Phillips Anna Evans , Schwarzenberg Sarah Jane , Singh Vikesh K. , Toledo Frederico G. S. , VanDalfsen Jill , Whitcomb David C. , Wu Bechien , Yadav Dhiraj
Published: December 2024

Both the clinical management and study of recurrent acute pancreatitis and chronic pancreatitis are complicated by significant heterogeneity in the etiology, mechanisms, symptoms, and complications of pancreatitis. The National Institutes of Diabetes and Digestive and Kidney Disease recently convened a workshop to address current knowledge and knowledge gaps in the field. Preclinical models that better replicate human disease are important for development of new therapies. Pain is often the most common and most difficult symptom to treat, as the causes are multifactorial and effective treatment may vary depending on whether pain is neuropathic or nociceptive in origin, and the placebo effect can complicate evaluation of the efficacy of medical and procedural interventions. Novel technologies like functional magnetic resonance imaging and virtual reality may offer novel means for assessing and treating pain, respectively. Clinical trial designs will need to consider best approaches to addressing the heterogeneity of chronic pancreatitis, including careful attention to designing eligibility criteria, and establishing accepted and validated core outcomes criteria for the field. The latter may be informed by consensus in pain research. Recruitment of participants into clinical trials has been challenging, often requiring multiple centers. Establishment of a clinical trials network would facilitate greater opportunities for therapeutic trials in pancreatitis.
Current Understanding of Therapeutic and Diagnostic Applications of Exosomes in Pancreatic Cancer
Authors: Shakerian Neda , Tafazoli Aida , Razavinia Amir , Sadrzadeh Aghajani Zahra , Bana Nikoo , Mard-Soltani Maysam , Khalesi Bahman , Hashemi Zahra Sadat , Khalili Saeed
Published: December 2024

Unusual symptoms, rapid progression, lack of reliable early diagnostic biomarkers, and lack of efficient treatment choices are the ongoing challenges of pancreatic cancer. Numerous research studies have demonstrated the correlation between exosomes and various aspects of pancreatic cancer. In light of these facts, exosomes possess the potential to play functional roles in the treatment, prognosis, and diagnosis of the pancreatic cancer. In the present study, we reviewed the most recent developments in approaches for exosome separation, modification, monitoring, and communication. Moreover, we discussed the clinical uses of exosomes as less invasive liquid biopsies and drug carriers and their contribution to the control of angiogenic activity of pancreatic cancer. Better investigation of exosome biology would help to effectively engineer therapeutic exosomes with certain nucleic acids, proteins, and even exogenous drugs as their cargo. Circulating exosomes have shown promise as reliable candidates for pancreatic cancer early diagnosis and monitoring in high-risk people without clinical cancer manifestation. Although we have tried to reflect the status of exosome applications in the treatment and detection of pancreatic cancer, it is evident that further studies and clinical trials are required before exosomes may be employed as a routine therapeutic and diagnostic tools for pancreatic cancer.
Curable giant hematoma due to small bowel mesenteric laceration after screening colonoscopy: a case report
Authors: Li Xue , Liu Chuntao , Zhang Lingye , Wang Yongjun , Zhang Shutian , Xing Jie
Published: December 2024

Introduction and importance:

Mesenteric laceration after screening colonoscopy is a rare and fatal complication. This case reported a giant hematoma due to a small intestinal mesenteric laceration after a screening colonoscopy.

Case description:

A 56-year-old woman complained of persistent dramatic abdominal pain after the screening colonoscopy. This patient has appendectomy, rheumatic heart disease, IgG4-related disease, type 2 diabetes mellitus, and coronary atherosclerotic heart disease. Blood tests showed hemoglobin concentration sharply fell to 87 g/L and computed tomography scans confirmed a 16.4 cm × 6.1 cm × 9.5 cm hematoma abdominal hematoma near the small intestine. Digital subtraction angiography consistently showed rough and disordered the fourth group of the superior mesenteric artery. The main diagnosis was mesenteric laceration of the small intestine following colonoscopy. The patient was treated with fasting, gastrointestinal decompression, rehydration, inhibition of gastric acid, and meropenem to fight infection, 4 U suspended red blood cells and 400 mL fresh frozen plasma. Finally, this patient was discharged after conservative treatment, and the abdominal hematoma was significantly shrunk after 3 months.

Clinical discussion:

Anticoagulants, a history of previous abdominal surgery, and IgG-RD leading to abdominal fibrosis were possible risk factors for mesenteric laceration. When the patient’s condition is complex and has no absolute indication for surgery, conservative management could be appropriately considered.

Conclusions:

We reported a case of abdominal hematoma due to colonoscopy. The successful conservative therapy may provide a novel experience for intra-abdominal hematoma treatment.
Berberine in combination with anti-PD-L1 suppresses hepatocellular carcinoma progression and metastasis via Erk signaling pathway
Authors: Miao Ganggang , Zhang Zhiyu , Wang Meiyan , Gu Xingwei , Xiang Dongxiao , Cao Hongyong
Published: December 2024

Background:

Berberine (BBR) is an isoquinoline alkaloid extracted from Huang Lian and other herbal medicines. It has been reported to play a crucial role in multiple metabolic diseases and cancers. Programmed cell death-1 (PD-L1) is known as the immune checkpoint; immunotherapy targeting PD1/PD-L1 axis can effectively block its pro-tumor activity. However, the effect of the combined use of BBR and anti-PD-L1 on hepatocellular carcinoma (HCC) has not been reported.

Methods:

Hep-3B and HCCLM3 cells were chosen as the experimental objects. To determine the potential anti-cancer activity of the combination of BBR and anti-PD-L1, we first treated v cells with BBR. The cell viability of Hep-3B and HCCLM3 with BBR treatment was measured by Cell Count Kit 8 assay. Cytometry by time-of-flight was performed to analyze tumor tissues after treatment with BBR and/or anti-PD-L1. Proliferation-, migration-, and invasion-related markers were measured by western blotting and immunohistochemistry.

Results:

The results showed that BBR significantly inhibited the proliferation of Hep-3B and HCCLM3.The combination treatment of BBR and anti-PD-L1 had a prominent inhibitory effect on HCC tumorigenesis. Cytometry by time-of-flight analysis indicated that BBR affects the immune subsets in the tumors. Besides, BBR and anti-PD-L1 inhibited the migration and invasion of HCC by inactivating the phosphorylation of Erk.

Conclusion:

Our study proposed that the combination treatment of BBR and anti-PD-L1 markedly inhibited the tumorigenesis of HCC by Erk signaling pathway. We hope our research can provide a new strategy for the potential of BBR as a therapeutic agent in the treatment of HCC.