Life, Volume 13, Issue 12 (December 2023) – 127 articles

4-Nonylphenol belongs to the alkylphenol group of chemicals, and its high occurrence in the environment can cause an adverse effect on human health. Breast milk can serve as a marker to take measure of human exposure to these chemicals through different routes of exposure. In this work, the influence of selected factors (the kind of water drank by the mothers; the consumption of fish, pork, and beef; wearing gloves; using nail polish, gel nails, vitamins, and medication) on the concentration on 4-nonylphenol in 89 breast milk samples was studied. The concentrations of nonylphenol in breast milk were determined by HPLC with fluorescence detection. The lowest and highest concentrations of 4-nonylphenol in breast milk were 0.97 ng/mL and 4.37 ng/mL, respectively. Statistical significance was observed for the consumption of pork (p = 0.048) and fish (0.041) in relation to the 4-nonylphenol concentration. Certain parameters (use of gel nails, beef consumption, and vitamin supplementation) were at the border of statistical significance (p = 0.06). Other parameters did not show any statistical significance. The results showed that breast milk in Slovakia does not contain a harmful dose of 4-nonylphenol and does not cause health problems. But it is necessary to continue this research and perform extended screening on a larger number of samples. Full article

Purpose: To measure the ocular motility parameters of the Developmental Eye Movement (DEM) test objectively, with an eye tracker in subjects with intellectual disability (ID). Methods: The DEM test was performed on 45 subjects with ID, while their eye movements were recorded with an eye tracker. Some objective parameters of ocular motility were obtained through each subtest (A, B, and C) of the full DEM test. Results: There was a significant positive correlation between the saccadic speed (cc: 0.537; p = 0.001) and length (cc: 0.368; p = 0.030) of both eyes for the same subject. People with a higher percentage of ID exhibited a greater number of fixations, saccades, and errors, and took longer to perform the DEM test than those with a lower ID percentage, who had greater numbers of these parameters than subjects without ID. Subjects without ID exhibited faster saccades, with a higher amplitude, than subjects with ID. Conclusions: The eye tracker quantifies ocular motility parameters involved in the DEM test in subjects with ID. Both eyes’ movements in subjects with ID were conjugated, exhibiting saccades of the same length and speed. All parameters were different in subjects with ID compared to those in subjects without ID, so normative tables specifically for subjects with ID are necessary. Full article

Orthohantaviruses are mainly carried and transmitted by wild rodents, although during the last decade, they have also been identified in multiple species of shrews and moles. Orthohantavirus, Orthohantavirus seewisense (Seewis virus, SWSV), first detected in Switzerland in a single Sorex araneus (Eurasian common shrew) specimen, has been further described in several European countries, including Croatia’s neighboring Slovenia and Hungary. Croatia is a well-known endemic region for several zoonotic agents including three different orthohantaviruses: Orthohantavirus puumalaense (PUUV), Orthohantavirus dobravaense (DOBV), and Orthohantavirus tulaense (TULV). In this study, nine shrews were tested and SWSV RNA was detected in liver, lung, and kidney belonging to two shrews (22.22%), one collected on Medvednica mountain in Zagreb County, and the other in the Stara Gradiška area in lowland Croatia. The phylogenetic analysis of the complete S segment’s open reading frame (ORF) and partial L-segment revealed that the Croatian sequences, when compared to sequences from the adjacent geographic regions, form a specific genetic lineage. Two SWSV-positive shrew species—Sorex araneus and Neomys milleri (Mediterranean water shrew)—were identified using barcode-based sequence analysis. Therefore, the SWSV detection in N. milleri throughout the course of this study is seen as a rare find in this shrew species. To our knowledge, this is the first molecular and phylogenetic analysis of SWSV in Croatia. Full article

Heterotopic ossification (HO) is the process of ectopic bone formation in the periarticular soft tissues and is usually formed in the elbow, hip and knee joint as a complication of trauma, burns, brain injury or surgical procedures. The development of HO around the elbow joint can cause a severe limitation of range of motion (ROM) and may affect daily activities of the patient. Treatment of ectopic bone formation around the elbow is a challenge for many surgeons. Non-operative treatment usually fails to restore the ROM of the elbow joint; thus, surgery is necessary to restore the function of the joint. In the past, many surgeons suggested that a delayed excision of HO, until maturation of the ectopic bone, is the best option in order to avoid any possible recurrence. However, many authors now suggest that this delay may lead to complications such as muscular atrophy and formation of soft tissue contractures that can cause a greater impairment of elbow function; thus, early excision is a better option and can better restore the elbow ROM. We performed a literature research of articles that investigated which is the best time of HO excision and we also evaluated if the tethering effect of HO can lead to a greater impairment of the elbow function. We found numerous studies suggesting that a limitation in ROM of the elbow can appear from the tethering of the ectopic bone formation and not only from primary HO. Concerning the HO excision, there were no significant differences between patients who underwent delayed and early excision, concerning the recurrence rate of HO around the elbow. Patients who underwent early excision had better restoration of elbow ROM; thus, early excision, combined with a rehabilitation program, is reported to be the best option for these patients. Full article

Background: The use of encapsulated cells for the in vivo delivery of biotherapeutics is a promising new technology to potentiate the effectiveness of cell-based therapies for veterinary and human application. One use of the technology is to locally activate chemotherapeutics to their short-lived highly active forms. We have previously shown that a stable clone of HEK293 cells overexpressing a cytochrome P450 enzyme that has been encapsulated in immunoprotective cellulose sulphate beads can be implanted near solid tumours in order to activate oxazaphosphorines such as ifosfamide and cyclophosphamide to the tumour-killing metabolite phosphoramide mustard. The efficacy of this approach has been shown in animal models as well as in human and canine clinical trials. In these previous studies, the oxazaphosphorine was only given twice. An analysis of the Kaplan–Meier plots of the results of the clinical trials suggest that repeated dosing might result in a significant clinical benefit. Aims: In this study, we aimed to (i) demonstrate the stable long-term expression of cytochrome P450 from a characterized, transfected cell clone, as well as (ii) demonstrate that one implanted dose of these encapsulated cytochrome P450-expressing cells is capable of activating multiple doses of ifosfamide in animal models. Methodology: We initially used cell and molecular methods to show cell line stability over multiple passages, as well as chemical and biological function in vitro. This was followed by a demonstration that encapsulated HEK293 cells are capable of activating multiple doses of ifosfamide in a mouse model of pancreatic cancer without being killed by the chemotherapeutic. Conclusion: A single injection of encapsulated HEK293 cells followed by multiple rounds of ifosfamide administration results in repeated anti-tumour activity and halts tumour growth but, in the absence of a functioning immune system, does not cause tumour regression. Full article

Klebsiella pneumoniae (K. pneumoniae) is a multidrug-resistance Gram-negative organism responsible for carbapenem-resistant infections. These challenges have inspired studies on the use of natural products as alternatives to conventional drugs. The aim of this study was to analyze the antibacterial and antioxidant effects of Ficus carica L. (fig) branch extracts and to perform in vivo animal experiments to better understand the absorption mechanisms of the antibacterial components during the digestion process after oral administration. The antibacterial components of the fig branch extracts were analyzed via gas chromatography-mass spectrometry (GC-MS). An in vivo animal study and liquid chromatography-triple quadrupole-tandem mass spectrometry (LC-QQQ-MS/MS) analyses were performed to analyze the deacetylation reactions of the fig extracts after oral administration in mice. Ultimately, the antibacterial effects of the fig extracts increased with the fractional distillation time. The fig extracts showed excellent antibacterial effects against K. pneumoniae, as well as Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Pseudomonas aeruginosa (P. aeruginosa). The three antibacterial and antioxidant components of the fig extracts were revealed to be eugenol, acetyleugenol, and psoralen. Interestingly, in this study, we identified acetyleugenol in the phenolic compounds of the fig extract for the first time. Through in vivo animal testing, we observed the deacetylation reaction of acetyleugenol to eugenol in the fig extract as digestion proceeded in the internal organs of the mice after oral administration. The results of this study suggest the use of natural fig extract as an effective therapeutic and prophylactic antibacterial agent for inflammation-related infections with a wide variety of biomedical applications. Full article

Perishable commodities like cassava necessitate effective postharvest preservation for various industrial applications. Hence, optimizing pretreatment processes and modeling drying kinetics hold paramount importance. This study aimed to optimize cassava pretreatment using the central composite design of a response surface methodology while also assessing microstructure and dehydration kinetics. Diverse chemical and thermal pretreatments were explored, encompassing sodium metabisulfite concentrations (0–4% w/w), citric acid concentrations (0–4% w/w), and blanching time (0–4 min). The four investigated responses were moisture content, whiteness index, activation energy (E_a), and effective moisture diffusivity (D_eff). Employing five established drying models, suitability was appraised after optimal pretreatment conditions were determined. The findings revealed that moisture content ranged from 5.82 to 9.42% db, whereas the whiteness index ranged from 87.16 to 94.23. D_eff and E_a ranged from 5.06 × 10⁻⁹ to 6.71 × 10⁻⁹ m²/s and 29.65–33.28 kJ/mol, respectively. The optimal pretreatment conditions for dried cassava were identified by optimizing the use of 1.31% citric acid, 1.03% sodium metabisulfite, and blanching time for 1.01 min. The microstructure indicated that particular chemical and thermal pretreatment configurations yielded particles in the shape of circular and elliptical granules. The logarithmic model provided the most accurate description of the dehydration kinetics, with the highest R² value (0.9859) and the lowest χ², RSME, and SSE values of 0.0351, 0.0015, and 0.0123, respectively. Full article

Several animal species have been found to be susceptible to SARS-CoV-2 infection. The occurrence of infection in dogs and cats living in close contact with owners deserves particular attention from public health authorities in a One Health approach. In this study, we conducted serological screening to identify SARS-CoV-2 exposure in the sera from dogs and cats in three regions of southern Italy sampled during the years 2021 and 2022. We collected 100 serum samples in 2021 (89 from dogs and 11 from cats) and 640 in 2022 (577 from dogs and 63 from cats). Overall, the ELISA positivity rate was found to be 2.7% (20/740), with higher seroprevalence in dogs. Serum neutralization tests confirmed positivity only in two samples collected from dogs, and the assays, performed with serologically distinct SARS-CoV-2 variants, showed variant-specific positivity. This paper shows that monitoring SARS-CoV-2 exposure in animals might be affected by the viral antigenic evolution, which requires continuous updates to the serological tests used. Serological surveys are useful in understanding the true extent of exposure occurring in specific animal populations, not suffering the same limitations as molecular tests, and could help in identifying the infecting virus if tests able to characterize the immune response are used. The use of variant-specific validated serological methods should always be considered in serosurvey studies in order to determine the real impact of emerging variants on animal populations and its implications for veterinary and human health, as well as to identify potential reservoirs of the virus and its evolutionary changes. Full article

Transspinal direct current stimulation (tsDCS) is a non-invasive technique used to modulate spinal cord activity. However, the effects and mechanisms of this stimulation are currently not comprehensively known. This study aimed to estimate the effect of different intensities of tsDCS applied at the level of cervical enlargement of the spinal cord (C7-Th1 segments) on the excitability of the corticospinal system (CSS) and the correction of motor skills in healthy subjects. The effect of tsDCS was estimated by the motor-evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS) in the primary motor cortex (M1). The study involved 54 healthy adults aged 22 ± 4 years. The application of 11 min anodal tsDCS at the level of the cervical spine C7-Th1 with a current intensity of 2.5 mA did not change the MEP amplitude of the upper limb muscles, in contrast to the data that we previously obtained with a current intensity of 1.5 mA. We also found no difference in the effect of 2.5 mA stimulation on motor skill correction in healthy subjects in the nine-hole peg test (9-HPT) and the serial reaction time task (SRT) as with 1.5 mA stimulation. Our data show that an increase in the intensity of stimulation does not lead to an increase in the effects but rather reduces the effects of stimulation. These results provide information about the optimally appropriate stimulation current intensities to induce CSS excitability and the ability of tsDCS to influence motor skills in healthy adults. Full article

Atypical polypoid adenomyoma (APAM) is a rare polypoid benign tumor of the uterus that causes irregular vaginal bleeding in women of reproductive age. It has the potential for malignant transformation, but it does not metastasize. APAM may coexist with endometrial hyperplasia and adenocarcinoma, usually leading to misdiagnosis. Histopathologically, it is a biphasic tumor, represented by the endometrioid glands with a complex histoarchitecture, with sometimes squamous morular metaplasia or cytologic atypia, interspersed with a fibromyomatous stroma. This tumor has a high incidence of recurrence. We present a very rare case of a 21-year-old patient, a virgin, without a significant medical history, with a bleeding mass occupying the vagina. The mass was excised using forceps, scissors, and a suture of the visible pedicle. After a four-year follow-up and no additional medical treatment, no relapse was observed. Given the risk of recurrence and progression, APAM might be treated via a hysterectomy in patients with no desire for pregnancy. Due to a lower recurrence rate, the conservative treatment of atypical polypoid adenomyoma performed via an operative hysteroscopy represents the best choice. Previously diagnosed in hysterectomy specimens, with the introduction of better-performing indirect imaging techniques, adenomyosis is a clinical entity that has the possibility of being diagnosed in the presurgical stage. Full article

Effective postoperative pain management is critical for recovery after orthopedic surgery, but often remains inadequate despite multimodal analgesia. This systematic review synthesizes evidence on innovative modalities for enhancing pain control following major orthopedic procedures. Fifteen randomized controlled trials and comparative studies evaluating peripheral nerve blocks, local anesthetic infiltration, cryotherapy, transcutaneous electrical stimulation, adjunct medications, and other techniques are included. Thematic analysis reveals that peripheral nerve blocks and local anesthetic infiltration consistently demonstrate reduced pain scores, opioid consumption, and side effects versus conventional analgesia alone. Oral multimodal medications also show promise as part of opioid-sparing regimens. Adjunctive approaches like cryotherapy, music, and dexmedetomidine require further research to optimize protocols. Despite promising innovations, critical knowledge gaps persist regarding comparative effectiveness, optimal interventions and dosing, combination strategies, cost-effectiveness, and implementation. High-quality randomized controlled trials using standardized protocols are essential to guide the translation of enhanced multimodal regimens into clinical practice. This review provides a framework for pursuing research priorities and advancing evidence-based postoperative pain management across orthopedic surgeries. Full article

An important feature of ruminal ciliates is their phenotypic plasticity, which makes their identification difficult. The common manifestation of the phenotypic plasticity in rumen ciliates is a change in their cell size and caudal spination. We analyzed various morphotypes of Epidinium with five caudal processes (spines) taken from the rumen of European bison (Bison bonasus). In the study, the cluster analysis and K-means analysis of morphometric data could not distinguish very similar morphotypes of Epidinium with five caudal processes. However, the morphotype of E. parvicaudatum prevailed (70%). The DNA of four individual E. parvicaudatum was isolated successfully from formaldehyde-preserved samples. The partial 18S rDNA gene sequences (about 350–400 bp) were identical to Epidinium sequences in GenBank (E. caudatum, a one-spine morphotype, and E. cattanei, a five-spine morphotype). It can be assumed that these short sequences cannot distinguish the differences between the Epidinium morphospecies. Complete gene sequences from various hosts and various molecular markers are necessary to reveal the validity of the Epidinium five-spine species. In conclusion, classical morphology should be supplemented with molecular data when more morphotypes of the rumen ciliate species are present in samples. Full article

We provide new support for habitable microenvironments in the near-subsurface of Mars, hosted in Fe- and Mg-rich rock units, and present a list of minerals that can serve as indicators of specific water–rock reactions in recent geologic paleohabitats for follow-on study. We modeled, using a thermodynamic basis without selective phase suppression, the reactions of published Martian meteorites and Jezero Crater igneous rock compositions and reasonable planetary waters (saline, alkaline waters) using Geochemist’s Workbench Ver. 12.0. Solid-phase inputs were meteorite compositions for ALH 77005, Nakhla, and Chassigny, and two rock units from the Mars 2020 Perseverance rover sites, Máaz and Séítah. Six plausible Martian groundwater types [NaClO₄, Mg(ClO₄)₂, Ca(ClO₄)₂, Mg-Na₂(ClO₄)₂, Ca-Na₂(ClO₄)₂, Mg-Ca(ClO₄)₂] and a unique Mars soil-water analog solution (dilute saline solution) named “Rosy Red”, related to the Phoenix Lander mission, were the aqueous-phase inputs. Geophysical conditions were tuned to near-subsurface Mars (100 °C or 373.15 K, associated with residual heat from a magmatic system, impact event, or a concentration of radionuclides, and 101.3 kPa, similar to <10 m depth). Mineral products were dominated by phyllosilicates such as serpentine-group minerals in most reaction paths, but differed in some important indicator minerals. Modeled products varied in physicochemical properties (pH, Eh, conductivity), major ion activities, and related gas fugacities, with different ecological implications. The microbial habitability of pore spaces in subsurface groundwater percolation systems was interrogated at equilibrium in a thermodynamic framework, based on Gibbs Free Energy Minimization. Models run with the Chassigny meteorite produced the overall highest H₂ fugacity. Models reliant on the Rosy Red soil-water analog produced the highest sustained CH₄ fugacity (maximum values observed for reactant ALH 77005). In general, Chassigny meteorite protoliths produced the best yield regarding Gibbs Free Energy, from an astrobiological perspective. Occurrences of serpentine and saponite across models are key: these minerals have been observed using CRISM spectral data, and their formation via serpentinization would be consistent with geologically recent-past H₂ and CH₄ production and sustained energy sources for microbial life. We list index minerals to be used as diagnostic for paleo water–rock models that could have supported geologically recent-past microbial activity, and suggest their application as criteria for future astrobiology study-site selections. Full article

Platelet-rich plasma is an autologous plasma containing platelets prepared from fresh whole blood drawn from a peripheral vein. Through processing, it can be prepared to contain supraphysiologic levels of platelets at three to five times greater than the level of normal plasma. PRP has been explored both in vivo and ex vivo in the human endometrium model in its ability to harness the intrinsic regenerative capacity of the endometrium. Intrauterine autologous PRP infusions have been shown to increase endometrial thickness and reduce the rate of intrauterine adhesions. In the setting of recurrent implantation failure, intrauterine infusion of PRP has been shown to increase clinical pregnancy rate. PRP also appears to hold a potential role in select patients with premature ovarian insufficiency, poor ovarian responders and in improving outcomes following frozen–thawed transplantation of autologous ovarian tissue. Further studies are required to explore the potential role of PRP in reproductive medicine further, to help standardise PRP protocols and evaluate which routes of administration are most effective. Full article

Chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), is a rare autoinflammatory bone disease primarily affecting children and adolescents. This review presents a comprehensive analysis of the intricate relationship between CNO and inflammatory bowel disease (IBD), shedding light on shared pathophysiological mechanisms and clinical management. A thorough literature review was conducted, encompassing 24 case reports involving 40 patients. The demographic distribution of patients revealed a near-equal gender ratio, with a median age of diagnosis at 12 years. The diagnosis patterns showed a higher proportion of CNO as the initial diagnosis, while Crohn’s disease was more prevalent than ulcerative colitis. The time interval between the clinical presentations varied, ranging from simultaneous detection to a substantial 15-year gap. Treatment modalities included nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, aminosalicylates, and biologic agents, such as infliximab, often overlapping in their use and suggesting shared pathophysiological pathways. Both conditions displayed systemic manifestations, and patients often responded well to immunosuppressive medications. The pathophysiology of CNO involves a genetic predisposition, cytokine dysregulation, and osteoclast activation. Dysregulated innate immunity results in immune cell infiltration into bones, causing sterile bone lesions. Notably, emerging evidence hints at a potential link between the microbiome and CNO. In contrast, IBD results from imbalanced mucosal immune responses to the intestinal microbiota. Polymorphisms in the promotor region of IL-10, common cytokines, immune cells, and genetic markers indicate shared immunological and genetic factors between CNO and IBD. Both conditions also involve extraintestinal symptoms. This analysis underscores the need for clinical awareness of the co-occurrence of CNO and IBD, especially among pediatric patients. A deepened understanding of the connections between these seemingly distinct diseases could lead to more effective management and improved patient outcomes. Full article

Although the importance of lipid homeostasis in neuronal function is undisputed, how they are regulated within neurons to support their unique function is an area of active study. NHR-49 is a nuclear hormone receptor functionally similar to PPARα, and a major lipid regulator in C. elegans. Although expressed in most tissues, little is known about its roles outside the intestine, the main metabolic organ of C. elegans. Here, using tissue- and neuron-type-specific transgenic strains, we examined the contribution of neuronal NHR-49 to cell-autonomous and non-autonomous nhr-49 mutant phenotypes. We examined lifespan, brood size, early egg-laying, and reduced locomotion on food. We found that lifespan and brood size could be rescued by neuronal NHR-49, and that NHR-49 in cholinergic and serotonergic neurons is sufficient to restore lifespan. For behavioral phenotypes, NHR-49 in serotonergic neurons was sufficient to control egg-laying, whereas no single tissue or neuron type was able to rescue the enhanced on-food slowing behavior. Our study shows that NHR-49 can function in single neuron types to regulate C. elegans physiology and behavior, and provides a platform to further investigate how lipid metabolism in neurons impact neuronal function and overall health of the organism. Full article

Inflammation plays a pivotal role in the development and progression of inflammatory bowel disease (IBD), by contributing to tissue damage and exacerbating the immune response. The investigation of serotonin receptor 2A (5-HT2A) ligands and transient receptor potential (TRP) channel ligands is of significant interest due to their potential to modulate key inflammatory pathways, mitigate the pathological effects of inflammation, and offer new avenues for therapeutic interventions in IBD. This study investigates the anti-inflammatory effects of 5-HT2A ligands, including psilocybin, 4-AcO-DMT, and ketanserin, in combination with TRP channel ligands, including capsaicin, curcumin, and eugenol, on the inflammatory response induced by tumor necrosis factor (TNF)-α and interferon (IFN)-γ in human 3D EpiIntestinal tissue. Enzyme-linked immunosorbent assay was used to assess the expression of pro-inflammatory markers TNF-α, IFN-γ, IL-6, IL-8, MCP-1, and GM-CSF. Our results show that psilocybin, 4-AcO-DMT, and eugenol significantly reduce TNF-α and IFN-γ levels, while capsaicin and curcumin decrease these markers to a lesser extent. Psilocybin effectively lowers IL-6 and IL-8 levels, but curcumin, capsaicin, and 4-AcO-DMT have limited effects on these markers. In addition, psilocybin can significantly decrease MCP-1 and GM-CSF levels. While ketanserin lowers IL-6 and GM-CSF levels, there are no effects seen on TNF-α, IFN-γ, IL-8, or MCP-1. Although synergistic effects between 5-HT2A and TRP channel ligands are minimal in this study, the results provide further evidence of the anti-inflammatory effects of psilocybin and eugenol. Further research is needed to understand the mechanisms of action and the feasibility of using these compounds as anti-inflammatory therapies for conditions like IBD. Full article

Background: Clinically relevant acute postoperative pancreatitis (CR-PPAP) after pancreaticoduodenectomy (PD) is a complication that may lead to the development of local and systemic consequences. The study aimed to identify risk factors for CR-PPAP and assess the impact of CR-PPAP on the postoperative course after PD. Methods: The study retrospectively analyzed data from 428 consecutive patients who underwent PD at a single center between January 2013 and December 2022. The presence of increased amylase activity in plasma, above the upper limit of normal 48 h after surgery, was checked. CR-PPAP was diagnosed when accompanied by disturbing radiological features and/or symptoms requiring treatment. We investigated the relationship between the occurrence of CR-PPAP and the development of postoperative complications after PD, and possible predictors of CR-PPAP. Results: The postoperative follow-up period was 90 days. Of the 428 patients, 18.2% (n = 78) had CR-PPAP. It was associated with increased rates of CR-POPF, delayed gastric emptying, occurrence of intra-abdominal collections, postoperative hemorrhage, peritonitis, and septic shock. Patients who developed CR-PPAP were more often reoperated (37.17% vs. 6.9%, p < 0.0001)) and had increased postoperative mortality (14.1% vs. 5.74%, p < 0.0001). Soft pancreatic parenchyma, intraoperative blood loss, small diameter of the pancreatic duct, and diagnosis of adenocarcinoma papillae Vateri were independent risk factors for CR-PPAP and showed the best performance in predicting CR-PPAP. Conclusions: CR-PPAP is associated with an increased incidence of postoperative complications after PD, worse treatment outcomes, and an increased risk of reoperation and mortality. Pancreatic consistency, intraoperative blood loss, width of the duct of Wirsung, and histopathological diagnosis can be used to assess the risk of CR-PPAP. Amylase activity 48 h after surgery > 161 U/L is highly specific in the diagnosis of CR-PPAP. Full article

Osteoarthritis (OA) is a degenerative joint condition with limited disease-modifying treatments currently. Palm tocotrienol-rich fraction (TRF) has been previously shown to be effective against OA, but its mechanism of action remains elusive. This study aims to compare serum metabolomic alteration in Sprague–Dawley rats with monosodium iodoacetate (MIA)-induced OA which were treated with palm TRF, glucosamine sulphate, or a combination of both. This study was performed on thirty adult male rats, which were divided into normal control (n = 6) and OA groups (n = 24). The OA group received intra-articular injections of MIA and daily oral treatments of refined olive oil (vehicle, n = 6), palm TRF (100 mg/kg, n = 6), glucosamine sulphate (250 mg/kg, n = 6), or a combination of TRF and glucosamine (n = 6) for four weeks. Serum was collected at the study’s conclusion for metabolomic analysis. The findings revealed that MIA-induced OA influences amino acid metabolism, leading to changes in metabolites associated with the biosynthesis of phenylalanine, tyrosine and tryptophan as well as alterations in the metabolism of phenylalanine, tryptophan, arginine and proline. Supplementation with glucosamine sulphate, TRF, or both effectively reversed these metabolic changes induced by OA. The amelioration of metabolic effects induced by OA is linked to the therapeutic effects of TRF and glucosamine. However, it remains unclear whether these effects are direct or indirect in nature. Full article

Lymphovascular space invasion (LVSI) is the presence of tumor emboli in the endothelial-lined space at the tumor body’s invasive edge. LVSI is one of three Sedlis criteria components—a prognostic tool for early cervical cancer (CC)—essential for indicating poor prognosis, such as lymph node metastasis, distant metastasis, or shorter survival rate. Despite its clinical significance, an in-depth comprehension of the molecular mechanisms or immune dynamics underlying LVSI in CC remains elusive. Therefore, this study investigated tumor-immune microenvironment (TIME) dynamics of the LVSI-positive group in CC. RNA sequencing included formalin-fixed paraffin-embedded (FFPE) slides from 21 CC patients, and differentially expressed genes (DEGs) were analyzed. Functional analysis and immune deconvolution revealed aberrantly enriched PI3K/Akt pathway activation and a heterogenic immune composition with a low abundance of regulatory T cells (Treg) between LVSI-positive and LVSI-absent groups. These findings improve the comprehension of LSVI TIME and immune mechanisms, benefiting targeted LVSI therapy for CC. Full article

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are examples of severe cutaneous adverse reactions to drugs (SCARs) with several international recommendations for global medical management, ranging from pharmacological systemic therapy to skin wound care. There is no defined best management of the skin wounds in SJS/TEN. The care of wounds is essential to initiate re-epithelialization. Our objective is to improve the cicatrization process, avoiding scarring due to deepening of the wounds, as well as prevent infections, achieve pain control, and avoid loss of serum proteins, fluids, and electrolytes. In this retrospective case series, we highlight the value of systemic therapy and the use of silver nitrate for wound management in four patients with TEN. Full article

This study explores the integration of Wide Field Optical Coherence Tomography (WF-OCT) with an AI-driven clinical decision support system, with the goal of enhancing productivity and decision making in breast cancer surgery margin assessment. A computationally efficient convolutional neural network (CNN)-based binary classifier is developed using 585 WF-OCT margin scans from 151 subjects. The CNN model swiftly identifies suspicious areas within margins with an on-device inference time of approximately 10 ms for a 420 × 2400 image. In independent testing on 155 pathology-confirmed margins, including 31 positive margins from 29 patients, the classifier achieved an AUROC of 0.976, a sensitivity of 0.93, and a specificity of 0.98. At the margin level, the deep learning model accurately identified 96.8% of pathology-positive margins. These results highlight the clinical viability of AI-enhanced margin visualization using WF-OCT in breast cancer surgery and its potential to decrease reoperation rates due to residual tumors. Full article

Trypanosoma cruzi, the protozoan causative of Chagas disease (ChD), exhibits striking genetic and phenotypic intraspecific diversity, along with ecoepidemiological complexity. Human-pathogen interactions lead to distinct clinical presentations of ChD. In 2009, an international consensus classified T. cruzi strains into six discrete typing units (DTUs), TcI to TcVI, later including TcBat, and proposed reproducible genotyping schemes for DTU identification. This article aims to review the impact of classifying T. cruzi strains into DTUs on our understanding of biological, ecoepidemiological, and pathogenic aspects of T. cruzi. We will explore the likely origin of DTUs and the intrinsic characteristics of each group of strains concerning genome organization, genomics, and susceptibility to drugs used in ChD treatment. We will also provide an overview of the association of DTUs with mammalian reservoirs, and summarize the geographic distribution, and the clinical implications, of prevalent specific DTUs in ChD patients. Throughout this review, we will emphasize the crucial roles of both parasite and human genetics in defining ChD pathogenesis and chemotherapy outcome. Full article

Heart failure (HF) and chronic kidney disease (CKD) are associated with high mortality. In both disorders, impaired iron homeostasis, mostly in the form of a functional iron deficiency, is a frequent co-morbidity. In HF, functional iron deficiency and management by i.v. iron supplementation have been proven to affect both prognosis and functional capacity. In the same context, iron supplementation is routine for the adequate management of renal anemia in CKD. In numerous recent studies in HF and in CKD, sodium–glucose transporter 2 (SGLT2) inhibitor treatment has been proven to significantly reduce mortality. Furthermore, the same trials showed that these drugs alleviate iron deficiency and anemia. These effects of SGLT2 inhibitors may be due to an amelioration of inflammation with reduced interleukin-6 (IL-6) and to an enhancement of autophagy with increased sirtuin 1 (SIRT1), both associated with modified production of hepcidin and enhanced ferritinophagy. However, the exact pathogenic basis of the beneficial SGLT2 inhibitor action is not fully elucidated. Nevertheless, effects on iron homeostasis might be a potential explanatory mechanism for the powerful SGLT2 inhibitors’ cardiovascular and renal outcome benefits. In addition, the interaction between iron supplementation and SGLT2 inhibitors and its potential impact on prognosis remains to be clarified by future studies. This review represents a significant effort to explore the complex relationships involved, seeking to elucidate the intricate mechanisms by which SGLT2 inhibitors influence iron homeostasis. Full article

Understanding and addressing post-radical prostatectomy (RP) erectile dysfunction (ED) is of paramount importance for clinicians. Cavernous nerve (CN) injury rat model studies have provided consistently promising experimental data regarding regaining erectile function (EF) after nerve damage-induced ED. However, these findings have failed to translate efficiently into clinical practice, with post-RP ED therapeutic management remaining cumbersome and enigmatic. This disparity highlights the need for further standardization and optimization of the elaborate surgical preparation protocols and multifaceted reporting parameters involved in reliable CN injury rat model experimentation. Even so, despite its technical complexity, this animal model remains instrumental in exploring the functional implications of RP, i.e., surgical lesions of the neurovascular bundles (NVBs). Herein, besides cavernous nerve (CN) dissection, injury, and electrostimulation, multiple pressure measurements, i.e., mean arterial pressure (MAP) and intra-cavernosal pressure (ICP), must also be achieved. A transverse cervical incision allows for carotid artery cannulation and MAP measurements. Conversely, ICP measurements entail circumcising the penis, exposing the ischiocavernous muscle, and inserting a needle into the corporal body. Finally, using an abdominal incision, the prostate is revealed, and the major pelvic ganglia (MPG) and CNs are dissected bilaterally. Specific surgical techniques are used to induce CN injuries. Herein, we provide a narrative and illustrative overview regarding these complex experimental procedures and their particular requirements, reflecting on current evidence and future research perspectives. Full article

The tiger grouper (Epinephelus fuscoguttatus), an important mariculture fish in Southeast Asia, faces increasing health issues in recent years. Phellodendri Cortex (PC) is a traditional Chinese herbal medicine that exhibits a variety of beneficial effects on tiger groupers. The effects of PC, however, varies with the period of dietary intervention. This study aims to investigate the long-term effects of 1% PC supplementation on tiger groupers, focusing on growth, immunity, disease resistance, and intestinal gene expression. The tiger groupers (with an initial mean weight of 27.5 ± 0.5 g) were fed with a diet of Phellodendri Cortex supplementation and a control diet for 8 weeks. Our results indicate that the long-term PC supplementation did not affect growth or Vibrio disease resistance in tiger groupers. However, the transcriptome analysis revealed potential damage to the structural and functional integrity of the groupers’ intestines. On the other hand, anti-inflammatory and cathepsin inhibition effects were also observed, offering potential benefits to fish enteritis prevention and therapy. Therefore, long-term PC supplementation in grouper culture should be applied with caution. Full article

Maintenance of the health of our oceans is critical for the survival of the oceanic food chain upon which humanity is dependent. Zooplanktonic copepods are among the most numerous multicellular organisms on earth. As the base of the primary consumer food web, they constitute a major biomass in oceans, being an important food source for fish and functioning in the carbon cycle. The potential impact of climate change on copepod populations is an area of intense study. Omics technologies offer the potential to detect early metabolic alterations induced by the stresses of climate change. One such omics approach is lipidomics, which can accurately quantify changes in lipid pools serving structural, signal transduction, and energy roles. We utilized high-resolution mass spectrometry (≤2 ppm mass error) to characterize the lipidome of three different species of copepods in an effort to identify lipid-based biomarkers of copepod health and viability which are more sensitive than observational tools. With the establishment of such a lipid database, we will have an analytical platform useful for prospectively monitoring the lipidome of copepods in a planned long-term five-year ecological study of climate change on this oceanic sentinel species. The copepods examined in this pilot study included a North Atlantic species (Calanus finmarchicus) and two species from the Gulf of Mexico, one a filter feeder (Acartia tonsa) and one a hunter (Labidocerca aestiva). Our findings clearly indicate that the lipidomes of copepod species can vary greatly, supporting the need to obtain a broad snapshot of each unique lipidome in a long-term multigeneration prospective study of climate change. This is critical, since there may well be species-specific responses to the stressors of climate change and co-stressors such as pollution. While lipid nomenclature and biochemistry are extremely complex, it is not essential for all readers interested in climate change to understand all of the various lipid classes presented in this study. The clear message from this research is that we can monitor key copepod lipid families with high accuracy, and therefore potentially monitor lipid families that respond to environmental perturbations evoked by climate change. Full article

Common carp (Cyprinus carpio L.) as a cultivated fish species has huge importance all over the world. According to FAO statistics, carp is the third most widely bred freshwater pond fish species; only two other Cyprinids (silver carp and grass carp) are bred in higher amounts. Carp is native all over Asia and in a large part of Europe. As a result of human intervention, at present, carp are widespread all over the world, except for the Arctic region. Carp breeding was launched in the antique period, in the ancient Chinese Empire and the Roman Empire. The presently applied method of breeding of common carp has a long evolution. From the effectiveness point of view, the propagation and early-life nursing are crucial parts of carp production, as they provide seed stocks for the further growing section. Without effective propagation, there is no intensive carp production. Nowadays, more advanced propagation methods are available all over the world; however, in the current review, only the main milestones and production efficiency of the propagation and nursing method used in the ponds of Eastern Central Europe are discussed. In the historical overview of carp reproduction, first the natural reproduction, then the semi-extensive and intensive hatchery propagation are presented and investigated in detail. The analysis focuses on the advantages and disadvantages of the method. In particular, the different important milestones of the advanced hatchery method are shown and explained. The effectiveness is proven even with practical calculations. Not only the reproduction, but the pond nursing method is also presented and discussed, concentrating on the management of evolutionarily adapted natural feeds (Zooplankton) and their effect on the survival of fish larvae. Full article

Schistosomiasis and soil-transmitted helminthiasis remain a public health concern in Tanzania. This study investigated the prevalence and intensities of Schistosoma haematobium, S. mansoni, and soil-transmitted helminths and associated factors in Itilima district, north-western Tanzania. A cross-sectional survey was conducted between August and September 2020 among 3779 primary schoolchildren in 62 primary schools and 1122 adults in 19 villages. Urine samples were obtained from each participant and examined visually for the presence of macrohaematuria, microhaematuria, and S. haematobium eggs using a urine dipstick and urine filtration test. A single stool sample was obtained from each participant and screened for S. mansoni and soil-transmitted helminths using the Kato Katz and formalin-ether concentration techniques. A questionnaire was administered to schoolchildren to elucidate the risk factors for schistosomiasis. The overall prevalence of S. haematobium in adults was 8.1% (95% confidence interval (CI), 6.6–9.8%). In total, 3779 schoolchildren had complete results from urine testing, and the overall prevalence of S. haematobium was 10.1% (95% CI, 9.1–11.1%). The prevalence of S. mansoni and soil-transmitted helminths was relatively low among both children and adults compared to S. haematobium. Factors associated with S. haematobium infection among schoolchildren were the mother’s occupation, children aged 11–15 years, and water contact behaviour. The odds of having schistosomiasis infection among children aged 11–15 are 40% higher than those aged 5–10 (95% confidence interval (CI), 10–80%, p = 0.04). Children of parents who are livestock keepers have 12.3 times higher odds of having infection compared to those who have small-scale businesses (95% CI, 1.0–5.4, p = 0.03). Children who are in contact with infested water more than three times a week have 2.1 times higher odds of having an infection compared to those who do not (95% CI, 2.1; 1.6–2.8, p < 0.001). The findings provide updated geographical information on prevalence, yielding insights into the planning and implementation of mass drug administration in rural Tanzania. Full article

The purpose of this study was to assess oxidative phosphorylation (OXPHOS) in mouse ovaries, determine the relative content of proteins that form the respiratory chain complexes and the main structures of the cytoskeleton, and determine the mRNA of the corresponding genes after hindlimb suspension for 96 h. After hindlimb suspension, the maximum rate of oxygen uptake increased by 133% (p < 0.05) compared to the control due to the complex I of the respiratory chain. The content of mRNA of genes encoding the main components of the respiratory chain increased (cyt c by 78%, cox IV by 56%, ATPase by 69%, p < 0.05 compared with the control). The relative content of cytoskeletal proteins that can participate in the processes of transport and localization of mitochondria does not change, with the exception of an increase in the content of alpha-tubulin by 25% (p < 0.05) and its acetylated isoform (by 36%, p < 0.05); however, the mRNA content of these cytoskeletal genes did not differ from the control. The content of GDF9 mRNA does not change after hindlimb suspension. The data obtained show that short-term exposure to simulated weightlessness leads to intensification of metabolism in the ovaries. Full article