Life, Volume 14, Issue 1 (January 2024) – 161 articles

Abscisic acid (ABA) is the most important phytohormone involved in the response to drought stress. Subclass II of SNF1-related kinase 2 (SnRK2) is an important signaling kinase related to ABA signal transduction. It regulates the phosphorylation of the target transcription factors controlling the transcription of a wide range of ABA-responsive genes in Arabidopsis thaliana. The transgenic poplars (Populus tremula × P. tremuloides, clone T89) ectopically overexpressing AtSnRK2.8, encoding a subclass II SnRK2 kinase of A. thaliana, have been engineered but almost no change in its transcriptome was observed. In this study, we evaluated osmotic stress tolerance and stomatal behavior of the transgenic poplars maintained in the netted greenhouse. The transgenic poplars, line S22, showed a significantly higher tolerance to 20% PEG treatment than non-transgenic controls. The stomatal conductance of the transgenic poplars tended to be lower than the non-transgenic control. Microscopic observations of leaf imprints revealed that the transgenic poplars had significantly higher stomatal closures under the stress treatment than the non-transgenic control. In addition, the stomatal index was lower in the transgenic poplars than in the non-transgenic controls regardless of the stress treatment. These results suggested that AtSnRK2.8 is involved in the regulation of stomatal behavior. Furthermore, the transgenic poplars overexpressing AtSnRK2.8 might have improved abiotic stress tolerance through this stomatal regulation. Full article

High temperatures associated with climate change may increase the severity of plant diseases. This study investigated the effect of heat shock treatment on host and non-host barley powdery mildew interactions using brassinosteroid (BR) mutants of barley. Brassinosteroids are plant steroid hormones, but so far little is known about their role in plant-fungal interactions. Wild type barley cultivar Bowman and its near-isogenic lines with disturbances in BR biosynthesis or signalling showed high compatibility to barley powdery mildew race A6, while cultivar Delisa and its BR-deficient mutants 522DK and 527DK were fully incompatible with this pathogen (host plant-pathogen interactions). On the other hand, Bowman and its mutants were highly resistant to wheat powdery mildew, representing non-host plant-pathogen interactions. Heat pre-treatment induced shifts in these plant-pathogen interactions towards higher susceptibility. In agreement with the more severe disease symptoms, light microscopy showed a decrease in papillae formation and hypersensitive response, characteristic of incompatible interactions, when heat pre-treatment was applied. Mutant 527DK, but not 522DK, maintained high resistance to barley powdery mildew race A6 despite heat pre-treatment. By 10 days after heat treatment and infection, a noticeable shift became apparent in the chlorophyll a fluorescence and in various leaf reflectance parameters at all genotypes. Full article

Secondary metabolites derived from plants are recognized as valuable products with several successful applications in the pharmaceutical, cosmetic, and food industries. The major limitation to the broader implementation of these compounds is their low manufacturing efficiency. Current efforts to overcome unprofitability depend mainly on biotechnological methods, especially through the application of plant in vitro cultures. This concept allows unprecedented bioengineering opportunities for culture system modifications with in situ product removal. The silica-based xerogels can be used as a novel, porous biomaterial characterized by a large surface area and high affinity to lipophilic secondary metabolites produced by plant tissue. This study aimed to investigate the influence of xerogel-based biomaterials functionalized with methyl, hydroxyl, carboxylic, and amine groups on Rindera graeca transgenic root growth and the production of naphthoquinone derivatives. The application of xerogel-based scaffolds functionalized with the methyl group resulted in more than 1.5 times higher biomass proliferation than for reference untreated culture. The naphthoquinone derivatives’ production was noted exclusively in culture systems supplemented with xerogel functionalized with methyl and hydroxyl groups. Applying chemically functionalized xerogels as in situ adsorbents allowed for the enhanced growth and productivity of in vitro cultured R. graeca transgenic roots, facilitating product isolation due to their selective and efficient accumulation. Full article

Pediatric Differentiated Thyroid Cancer (pedDTC) is a rare pediatric malignancy with an increasing incidence over time. To date, there is a paucity of literature specifically addressing pedDTC within the context of Middle Eastern ethnicity. This retrospective study aimed to assess the risk-stratifying factors for overall survival (OS) and event-free survival (EFS) in pediatric DTC patients from Iraq and Jordan. The medical records of 81 patients from two tertiary cancer institutes were retrieved. Kaplan–Meier analysis was employed to investigate OS and EFS, and the Cox proportional hazards model was employed to estimate hazard ratios. All patients underwent surgery and radioactive iodine therapy, with a median age of 14 and an interquartile range of 12–15. Lymph node involvement was observed in 55% of cases, while distant metastases were present in 13.5%. After a median follow-up period of 68 months, the 10-year survival rate was determined to be 94%, while the 10-year EFS rate was 58%. EFS was negatively impacted by cervical lymph node metastases and early age of diagnosis (p ≤ 0.01, each). Therefore, pediatrics with initial cervical lymph node metastases and those diagnosed before puberty tend to experience poorer EFS, which may justify the need for more aggressive management plans. Full article

Intermittent hypoxia (IH) is a central characteristic of sleep apnea syndrome (SAS), and it subjects cells in the body to repetitive apnea, chronic hypoxia, oxygen desaturation, and hypercapnia. Since SAS is linked to various serious cardiovascular complications, especially hypertension, many studies have been conducted to elucidate the mechanism of hypertension induced by SAS/IH. Hypertension in SAS is associated with numerous cardiovascular disorders. As hypertension is the most common complication of SAS, cell and animal models to study SAS/IH have developed and provided lots of hints for elucidating the molecular mechanisms of hypertension induced by IH. However, the detailed mechanisms are obscure and under investigation. This review outlines the molecular mechanisms of hypertension in IH, which include the regulation systems of reactive oxygen species (ROS) that activate the renin–angiotensin system (RAS) and catecholamine biosynthesis in the sympathetic nervous system, resulting in hypertension. And hypoxia-inducible factors (HIFs), Endotheline 1 (ET-1), and inflammatory factors are also mentioned. In addition, we will discuss the influences of SAS/IH in cardiovascular dysfunction and the relationship of microRNA (miRNA)s to regulate the key molecules in each mechanism, which has become more apparent in recent years. These findings provide insight into the pathogenesis of SAS and help in the development of future treatments. Full article

Introduction: Idiopathic pulmonary fibrosis is a chronic progressive lung disease of unknown cause with a high associated mortality. We aimed to compare the impact of chronic medical conditions on hospital outcomes of patients with acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). Methods: This was a retrospective cohort study using the NIS database from 2016 to 2018. We included patients aged 60 and older hospitalized in academic medical centers with the diagnoses of IPF and acute respiratory failure. We examined factors associated with hospital mortality and length of stay (LOS) using survey-weighted multivariate logistic and negative binomial regression. Results: Out of 4975 patients with AE-IPF, 665 (13.4%) did not survive hospitalization. There was no difference in the mean age between survivors and non-survivors. Patients were more likely to be male, predominantly white, and have Medicare coverage. Most non-survivors were from households with higher median income. Hospital LOS was longer among non-survivors than survivors (9.4 days vs. 9.8 days; p < 0.001). After multivariate-logistic regression, diabetes was found to be protective (aOR 0.62, 95% CI 0.50–0.77; p < 0.0001) while chronic kidney disease (CKD) conferred a significantly higher risk of death after AE-IPF (aOR 6.85, 95% CI 1.90–24.7; p = 0.00). Our multivariate adjusted negative binomial regression model for LOS identified obesity (IRR 0.85, 95% CI 0.76–0.94; p ≤ 0.00) and hypothyroidism (IRR 0.90, 95% CI 0.83–0.98; p = 0.02) to be associated with shorter hospital LOS. Conclusions: Our results suggest that CKD is a significant contributor to hospital mortality in AE-IPF, and diabetes mellitus may be protective. Obesity and hypothyroidism are linked with shorter hospital LOS among patients hospitalized with AE-IPF in US academic medical centers. Full article

The skin’s protective mechanisms, in some cases, are not able to counteract the destructive effects induced by UV radiations, resulting in dermatological diseases, as well as skin aging. Nutlin-3, a potent drug with antiproliferative activity in keratinocytes, can block UV-induced apoptosis by activation of p53. In the present investigation, ethosomes and transethosomes were designed as delivery systems for nutlin-3, with the aim to protect the skin against UV damage. Vesicle size distribution was evaluated by photon correlation spectroscopy and morphology was investigated by cryogenic transmission electron microscopy, while nutlin-3 entrapment capacity was evaluated by ultrafiltration and HPLC. The in vitro diffusion kinetic of nutlin-3 from ethosomes and transethosomes was studied by Franz cell. Moreover, the efficiency of ethosomes and transethosomes in delivering nutlin-3 and its protective role were evaluated in ex vivo skin explants exposed to UV radiations. The results indicate that ethosomes and transethosomes efficaciously entrapped nutlin-3 (0.3% w/w). The ethosome vesicles were spherical and oligolamellar, with a 224 nm mean diameter, while in transethosome the presence of polysorbate 80 resulted in unilamellar vesicles with a 146 nm mean diameter. The fastest nutlin-3 kinetic was detected in the case of transethosomes, with permeability coefficients 7.4-fold higher, with respect to ethosomes and diffusion values 250-fold higher, with respect to the drug in solution. Ex vivo data suggest a better efficacy of transethosomes to promote nutlin-3 delivery within the skin, with respect to ethosomes. Indeed, nutlin-3 loaded transethosomes could prevent UV effect on cutaneous metalloproteinase activation and cell proliferative response. Full article

There has been a substantial increase in the number of cases of invasive fungal infections worldwide, which is associated with a growing number of immunosuppressed patients and a rise in antifungal resistance. Some fungi that were previously considered harmless to humans have become emerging pathogens. One of them is Purpureocillium lilacinum, a ubiquitous filamentous fungus commonly found in the environment, especially in the air and soil. P. lilacinum belongs to a bigger group of hyaline fungi that cause hyalohyphomycosis, a fungal infection caused by fungi with colorless hyphae. Although this is a heterogeneous group of fungi, there are similarities regarding their ubiquity, ways of transmission, affected patients, and difficulties in diagnostics and treatment. In hyalohyphomycosis, the skin is one of the most affected organs, which is why the involvement of dermatologists is crucial for the initial assessment, since the timely recognition and early diagnosis of this condition can prevent life-threatening infections and death. In this review, we covered cutaneous hyalohyphomycosis caused by P. lilacinum and other fungi in the same group, including Fusarium, Penicilium, Scedosporium, Scopulariopsis, Acremonium, and Trichoderma genera. Full article

Cockroaches harbor two coexisting symbiotic systems: the obligate endosymbiont Blattabacterium cuenotii, and a complex gut microbiota. Blattabacterium is the only bacterium present in the eggs, as the gut microbiota is acquired by horizontal transmission after hatching, mostly through coprophagy. Blattella germanica, a cosmopolitan omnivorous cockroach living in intimate association with humans, is an appropriate model system for studying whether the gut microbiota is essential for the cockroach’s survival, development, or welfare. We obtained a germ-free cockroach population (i.e., containing normal amounts of the endosymbiont, but free of microbes on the insects’ surface and digestive tract). Non-significant differences with the controls were detected in most fitness parameters analyzed, except for a slight shortening in the hatching time of the second generation and a reduction in female weight at 10 days after adult ecdysis. The latter is accompanied by a decrease in uric acid reserves. This starvation-like phenotype of germ-free B. germanica suggests that the microbiota is not essential in this species for survival and development throughout its complete life cycle, but it could participate in complementation of host nutrition by helping with food digestion and nutrient absorption. Full article

The levels and potential role of prolactin (PRL) in the brain under conditions of acute systemic hypoxia were examined, focusing on the accumulation of PRL in cerebrospinal fluid (CSF) and its effects on neuronal activity and injury. The amount of PRL in the brain was investigated using brain tissues from forensic autopsy cases. We counted the number of neurites that formed in human primary neurons (HNs) after the addition of PRL. Furthermore, HNs supplemented with PRL or triiodothyronine (T3) were exposed to hypoxic conditions, and the dead cells were counted. The results showed correlations between brain PRL and CSF PRL levels. Additionally, PRL accumulation in the brain was observed in cases of asphyxia. In vitro experimental findings indicated increased neurite formation in the HNs treated with PRL. Moreover, both PRL and T3 demonstrated neuroprotective effects against hypoxia-induced neuronal cell death, with PRL showing stronger neuroprotective potential than T3. These results suggest that PRL accumulates in the brain during hypoxia, potentially influences neuronal activity, and exhibits neuroprotective properties against hypoxia-induced neuronal injury. Full article

Introduction: Mini-invasive surgical (MIS) approaches to total hip replacement (THR) are becoming more popular and increasingly adapted into practice. THR via the direct anterior approach (MIS DAA) has become a rather controversial topic in hip arthroplasty literature in the last decades. Our retrospective observational study focuses on the prevalence of one approach-specific complication—lateral femoral cutaneous nerve (LFCN) iatrogenic lesion—and tries to clarify the possible pathogenesis of this injury. Methods: This is a retrospective single-cohort observational single-center and single-surgeon study. Our patient records were searched for the period from 2015 to 2017—after a safe period of time after the learning curve for MIS DAA. All intra- and post-operative lesions of the LFCN were recorded. Lesion of the LFCN was confirmed by a neurological examination. Minimum patient follow-up was 2 years. Results: This study involved 417 patients undergoing single-side THR via MIS DAA. Patients were examined on follow-up visits at 6 weeks, 6 months, 1 year, and 2 years after surgery. There were 17 cases of LCFN injury at the 6 weeks early follow-up visit (4.1%). All cases of clinically presenting LFCN injury resolved at the 2-year follow-up ad integrum. Discussion: Possible explanations of such neurological complications are direct iatrogenic injury, vigorous traction, hyperextension, or extreme external rotation of the operated limb. Use of a traction table or concomitant spinal pathology and deformity also play a role. Prevention involves stepwise adaptation of the approach during the learning curve period by attending cadaver lab courses, rational use of traction and hyperextension, and careful surgical technique in the superficial and deep fascial layers. Dynamometers could be used to visualise the limits of manipulation of the operated limb. Conclusions: Neurological complications are not as rare but questionably significant in patients undergoing THR via the DAA. Incidental finding of LFCN injury has no effect on the functional outcome of the artificial joint. It can lead to lower subjective satisfaction of patients with the operation, which can be avoided with careful education and management of expectations of the patients. Full article

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women that is characterized by fluid-filled sacs in the ovaries and various symptoms, including high androgen levels, endometrial irregularities, and cysts. Although the main cause of PCOS remains unknown, it has been linked to genetic, endocrine, and metabolic factors, and there are several treatment options, including lifestyle modifications, medications, and surgery. Natural products such as medicinal plants and fruits are being explored as potential treatments for PCOS because of their bioactive compounds with pharmacological effects related to antioxidant, antimicrobial, anticancer, and antidiabetic properties. Some of these compounds improve insulin sensitivity, reduce inflammation, and enhance glucose metabolism, thereby benefiting patients with PCOS. This mini-review examined the effects of natural products on PCOS, including their effects on ovarian histological changes, blood glucose, sex hormones, and lipid profiles, based on animal and human studies. This study suggests that the use of natural products as complementary medicines can be a promising resource for the development of effective therapeutics for PCOS; however, further research is needed to fully understand their benefits. Full article

The seasonal changes in environmental conditions can alter the growth states of host plants, thereby affecting the living environment of endophytes and forming different endophytic communities. This study employs Illumina MiSeq next-generation sequencing to analyze the 16SrRNA and ITS rDNA of endophytes in 24 samples of Actinidia arguta stem tissues across different seasons. The results revealed a high richness and diversity of endophytes in Actinidia arguta, with significant seasonal variations in microbial community richness. This study identified 897 genera across 36 phyla for bacteria and 251 genera across 8 phyla for fungi. Notably, 69 bacterial genera and 19 fungal genera significantly contributed to the differences in community structure across seasons. A distinctive feature of coexistence in the endophytic community, both specific and conservative across different seasons, was observed. The bacterial community in winter demonstrated significantly higher richness and diversity compared to the other seasons. Environmental factors likely influence the optimal timing for endophyte colonization. Solar radiation, temperature, precipitation, and relative humidity significantly impact the diversity of endophytic bacteria and fungi. In addition, seasonal variations show significant differences in the nutritional modes of fungal endophytes and the degradation, ligninolysis, and ureolysis functions of bacterial endophytes. This study elucidates the potential role of endophytes in assisting Actinidia arguta in adapting to seasonal changes and provides a theoretical basis for further exploration of functional microbial strains. Full article

Chickpeas (Cicer arietinum L.) are a valuable legume crop due to their nutritional value. To maintain chickpea productivity and avoid the adverse effects of climate change on soil and plant processes, it is crucial to address demand. Achieving this necessitates implementing sustainable agricultural practices incorporating the use of biostimulants, adaptable crops for arid conditions, as well as pest and disease-resistant crops that are sustainable over time. Three varieties of chickpeas were analysed to determine the effect of two different biostimulant application methods on both germination and vegetative growth. Possible effects due to location were also examined by conducting tests at two different sites. Significant variations in biostimulant response were evident only during the germination period, but not during the vegetative development stage, where the observed statistical differences were influenced more by the location or variety of chickpeas employed. Furthermore, this study examined the effect of biostimulants on nutrient cycling within the soil–plant microbiota system. Nitrogen-fixing bacteria (NFB) are present in the soil of chickpea crops at an order of magnitude of 10⁷ CFU/g DS. Additionally, an average concentration of 10⁶ CFU/g DS of phosphorus-mobilising bacteria was observed. Applying biostimulants (BioE) to seeds resulted in a successful germination percentage (GP) for both Amelia (AM) and IMIDRA 10 (IM) varieties. Full article

Illegal wildlife trade is currently on the rise, and it is becoming one of the most lucrative crime sectors. The rarer the species, the higher the demand. Wildlife trade falls under international regulations, such as the CITES convention. Proving that this convention has been violated is a complex process and can be very difficult to do. DNA analysis methods remain (in many cases) the only way to determine whether a certain specimen originated from a protected animal species, a specific individual, or a species in which it is legal to trade. Tanned animal hides are a specific type of specimen. With this type of biological material, obtaining amplifiable DNA is often difficult. This pilot study aimed to map the effect of the chemicals used in the tanning process on the degradation of the DNA yielded from such samples. The DNA was quantified using two different approaches: qPCR and Qubit fluorometry. The degree of DNA fragmentation was assessed by determining the degradation index. The results indicate that reagents containing chromium have the greatest influence on DNA degradation. However, by using the presented protocol, enough amplifiable DNA can be obtained from hides treated with aluminum-based reagents. Full article

Background: Immune checkpoint inhibitors (ICI) are one of the most effective therapies in oncology, albeit associated with various immune-related adverse events also affecting the cardiovascular system. Methods: We aimed to investigate the effect of ICI on arterial 2-[¹⁸F]FDG uptake by using 2-[¹⁸F]FDG PET/CT imaging pre/post treatment in 47 patients with lung cancer. Maximum 2-[¹⁸F]FDG standardized uptake values (SUVmax) and target-to-background ratios (TBRs) were calculated along six arterial segments. We classified the arterial PET lesions by pre-existing active inflammation (cut-off: TBRpre ≥ 1.6). 2-[¹⁸F]FDG metabolic activity pre/post treatment was also quantified in bone marrow, spleen, and liver. Circulating blood biomarkers were additionally collected at baseline and after immunotherapy. Results: ICI treatment resulted in significantly increased arterial inflammatory activity, detected by increased TBRs, in all arterial PET lesions analyzed. In particular, a significant elevation of arterial 2-[¹⁸F]FDG uptake was only recorded in PET lesions without pre-existing inflammation, in calcified as well as in non-calcified lesions. Furthermore, a significant increase in arterial 2-[¹⁸F]FDG metabolic activity after immunotherapy was solely observed in patients not previously treated with chemotherapy or radiotherapy as well as in those without CV risk factors. No significant changes were recorded in either 2-[¹⁸F]FDG uptake of bone marrow, spleen and liver after treatment, or the blood biomarkers. Conclusions: ICI induces vascular inflammation in lung cancer patients lacking pre-existing arterial inflammation. Full article

In recent times, there have been notable changes in cardiovascular medicine, propelled by the swift advancements in artificial intelligence (AI). The present work provides an overview of the current applications and challenges of AI in the field of heart failure. It emphasizes the “garbage in, garbage out” issue, where AI systems can produce inaccurate results with skewed data. The discussion covers issues in heart failure diagnostic algorithms, particularly discrepancies between existing models. Concerns about the reliance on the left ventricular ejection fraction (LVEF) for classification and treatment are highlighted, showcasing differences in current scientific perceptions. This review also delves into challenges in implementing AI, including variable considerations and biases in training data. It underscores the limitations of current AI models in real-world scenarios and the difficulty in interpreting their predictions, contributing to limited physician trust in AI-based models. The overarching suggestion is that AI can be a valuable tool in clinicians’ hands for treating heart failure patients, as far as existing medical inaccuracies have been addressed before integrating AI into these frameworks. Full article

The excessive use of synthetic pesticides has detrimental impacts on humans, non-target organisms, and the environment. Insect pest management strategies are shifting toward biopesticides, which can provide a feasible and environmentally friendly green solution to the pest problem. The key objective of the present research work was the preparation of Mentha piperita-based nanobiopesticides with enhanced stability, solubility, and pesticidal potential. Nanobiopesticides based on the Mentha piperita extract were prepared using the antisolvent precipitation method. The central composite design of response surface methodology (RSM) was utilized to optimize different process parameters, e.g., the amounts of the stabilizer and plant extract. The nanosuspension of Mentha piperita prepared with the stabilizer SLS showed a particle size of 259 nm and a polydispersity index of 0.61. The formulated biopesticides in the form of nanosuspensions showed good antibacterial activities as compared to the Mentha piperita extract against two phytopathogenic bacterial strains, Clavibacter michiganensis and Pseudomonas syringae. The M. piperita nanosuspension had higher antifungal efficacy against A. niger and F. oxysporum than the Mentha piperita extract. The M. piperita extract and its nanosuspensions were tested for pesticidal activity against the stored-grain insects Tribolium castaneum and Sitophilus oryzae. Mentha piperita-based nanobiopesticides demonstrated significantly high (p  <  0.05) average mortality of 84.4% and 77.7% against Tribolium castaneum and Sitophilus oryzae, respectively. Mentha piperita-based nanobiopesticides showed enhanced pesticidal potential and could be used as a good alternative to synthetic chemical pesticides. Full article

In physiological conditions, the intracellular chloride concentration is much lower than the extracellular. As GABA_A channels are permeable to anions, the reversal potential of GABA_A is very close to that of Cl⁻, which is the most abundant free anion in the intra- and extracellular spaces. Intracellular chloride is regulated by the activity ratio of NKCC1 and KCC2, two chloride-cation cotransporters that import and export Cl⁻, respectively. Due to the closeness between GABA_A reversal potential and the value of the resting membrane potential in most neurons, small changes in intracellular chloride have a major functional impact, which makes GABA_A a uniquely flexible signaling system. In most neurons of the adult brain, the GABA_A reversal potential is slightly more negative than the resting membrane potential, which makes GABA_A hyperpolarizing. Alterations in GABA_A reversal potential are a common feature in numerous conditions as they are the consequence of an imbalance in the NKCC1-KCC2 activity ratio. In most conditions (including Alzheimer’s disease, schizophrenia, and Down’s syndrome), GABA_A becomes depolarizing, which causes network desynchronization and behavioral impairment. In other conditions (neonatal inflammation and neuropathic pain), however, GABA_A reversal potential becomes hypernegative, which affects behavior through a potent circuit deactivation. Full article

With the conventional mechanical rotation measurement of joints, only static measurements are possible with the patient at rest. In the future, it would be interesting to carry out dynamic rotation measurements, for example, when walking or participating in sports. Therefore, a measurement method with an elastic polymer-based capacitive measuring system was developed and validated. In our system, the measurement setup was comprised of a capacitive strain gauge made from a polymer, which was connected to a flexible printed circuit board. The electronics integrated into the printed circuit board allowed data acquisition and transmission. As the sensor strip was elongated, it caused a change in the spacing between the strain gauge’s electrodes, leading to a modification in capacitance. Consequently, this alteration in capacitance enabled the measurement of strain. The measurement system was affixed to the knee by adhering the sensor to the skin in alignment with the anterolateral ligament (ALL), allowing the lower part of the sensor (made of silicone) and the circuit board to be in direct contact with the knee’s surface. It is important to note that the sensor should be attached without any prior stretching. To validate the system, an in vivo test was conducted on 10 healthy volunteers. The dorsiflexion of the ankle was set at 2 Nm using a torque meter to eliminate any rotational laxity in the ankle. A strain gauge sensor was affixed to the Gerdii’s tubercle along the course of the anterolateral ligament, just beneath the lateral epicondyle of the thigh. In three successive measurements, the internal rotation of the foot and, consequently, the lower leg was quantified with a 2 Nm torque. The alteration in the stretch mark’s length was then compared to the measured internal rotation angle using the static measuring device. A statistically significant difference between genders emerged in the internal rotation range of the knee (p = 0.003), with female participants displaying a greater range of rotation compared to their male counterparts. The polymer-based capacitive strain gauge exhibited consistent linearity across all measurements, remaining within the sensor’s initial 20% strain range. The comparison between length change and the knee’s internal rotation angle revealed a positive correlation (r = 1, p < 0.01). The current study shows that elastic polymer-based capacitive strain gauges are a reliable instrument for the internal rotation measurement of the knee. This will allow dynamic measurements in the future under many different settings. In addition, significant gender differences in the internal rotation angle were seen. Full article

The MYB transcription factor family can regulate biological processes such as ABA signal transduction to cope with drought stress, but its evolutionary mechanism and the diverse pathways of response to drought stress in different species are rarely reported. In this study, a total of 4791 MYB family members were identified in 908,757 amino acid sequences from 12 model plants or crops using bioinformatics methods. It was observed that the number of MYB family members had a linear relationship with the chromosome ploidy of species. A phylogenetic analysis showed that the MYB family members evolved in subfamily clusters. In response to drought stress, the pathways of MYB transcription factor families exhibited species-specific diversity, with closely related species demonstrating a higher resemblance. This study provides abundant references for drought resistance research and the breeding of wheat, soybean, and other plants. Full article

Consideration of the individual carpal bone characteristics of the wrist plays a key role in well-functioning biomedical devices and successful surgical procedures. Although geometric differences and individual bone sizes have been analyzed in the literature, detailed morphologic descriptions and correlations covering the entire wrist reported in a clinical context are lacking. This study aimed to perform a comprehensive and automatic analysis of the wrist morphology using the freely available “Open Source Carpal Database” (OSCD). We quantified the size of each of the individual carpal bones and their combination. These sizes were extracted in n = 117 datasets of the wrist of the OSCD in anatomical directions and analyzed using descriptive statics and correlation analysis to investigate the morphological characteristics under sex-specific aspects and to provide regression plots and equations to predict individual carpal bone sizes from the proximal and distal row dimensions. The correlations in the proximal row were higher compared to the distal row. We established comprehensive size correlations and size rations and found that there exist statistical differences between sex, particularly of the scaphoid. The regression plots and equations we provided will assist surgeons in a more accurate preoperative morphological evaluation for therapy planning and may be used for future anatomically inspired orthopedic biomedical device designs. Full article

A 50-year-old male presented to the emergency room after experiencing sudden right upper limb facial numbness and dysphasia, followed by full recovery. A brain CT scan showed hyperdense lesions within the left hemispheric sulcus, which raised suspicion of spontaneous subarachnoid hemorrhage. A T1-weighted MRI showed multiple tiny leptomeningeal enhancements in the same area, and a digital subtraction angiography showed no signs of vascular abnormality. Cerebrospinal fluid cytology revealed atypical melanin-containing cells with minimal pleomorphism. One month later, the patient developed sixth nerve palsy, which was determined to be due to intracranial hypertension. Multiple giant nevi on the legs, trunk, and scalp were also observed. A skin biopsy showed well-defined and symmetrical proliferation of melanocytic nevus cell nests in the dermis. An open biopsy was performed due to the suspicious leptomeningeal lesions, which surprisingly revealed diffuse and thick black-colored tissue infiltration of the leptomeninges. Pathology confirmed the diagnosis of meningeal melanocytosis. A ventriculoperitoneal shunt was then placed, and the patient’s neurological symptoms gradually improved. Based on the presence of multiple giant nevi on the patient’s skin and the finding of diffuse meningeal melanocytosis during the open biopsy, the patient was diagnosed with neurocutaneous melanosis. The patient received 6 cycles triweekly of Ipilimumab and Nivolumab 8 months after initial diagnosis. Unfortunately, the disease progressed and the patient passed away 14 months after initial diagnosis. Full article

(1) Importance of problem: Breast cancer accounted for 685,000 deaths globally in 2020, and half of all cases occur in women with no specific risk factor besides gender and age group. During the last four decades, we have seen a 40% reduction in age-standardized breast cancer mortality and have also witnessed a reduction in the medium age at diagnosis, which in turn means that the number of mastectomies performed for younger women increased, raising the need for adequate breast reconstructive surgery. Advances in oncological treatment have made it possible to limit the extent of what represents radical surgery for breast cancer, yet in the past decade, we have seen a marked trend toward mastectomies in breast-conserving surgery-eligible patients. Prophylactic mastectomies have also registered an upward trend. This trend together with new uses for breast reconstruction like chest feminization in transgender patients has increased the need for breast reconstruction surgery. (2) Purpose: The purpose of this study is to analyze the types of reconstructive procedures, their indications, their limitations, their functional results, and their safety profiles when used during the integrated treatment plan of the oncologic patient. (3) Methods: We conducted an extensive literature review of the main reconstructive techniques, especially the autologous procedures; summarized the findings; and presented a few cases from our own experience for exemplification of the usage of breast reconstruction in oncologic patients. (4) Conclusions: Breast reconstruction has become a necessary step in the treatment of most breast cancers, and many reconstructive techniques are now routinely practiced. Microsurgical techniques are considered the “gold standard”, but they are not accessible to all services, from a technical or financial point of view, so pediculated flaps remain the safe and reliable option, along with alloplastic procedures, to improve the quality of life of these patients. Full article

Background: Sortilin1 (SORT1) is a ubiquitously expressed transporter involved in sorting or clearing proteins and is pathologically linked to tissue fibrosis and calcification. Targeting SORT1 may have potential clinical efficacy in controlling or reversing cardiovascular fibrosis and/or calcification. Hence, this study assessed the protein–protein network of human SORT1 and its targetability using known nutra-/pharmaceuticals. Material and methods: Network proteins of human SORT1 were identified using the String database, and the affinity of the protein–protein interaction of this network was analysed using Chimera software (Chimera-1.17.3-mac64). The tissue-specific expression profile of SORT1 was evaluated and assessed for enrichment in different cell types, including immune cells. A library of in-house small molecules and currently used therapeutics for cardiovascular diseases were screened using AutoDock Vina to assess the targetability of human SORT1. The concentration affinity (CA) ratio of the small molecules was estimated to assess the clinical feasibility of targeting SORT1. Results: IGF2R, NTRK2, GRN and GGA1 were identified as high-affinity interaction networks of SORT1. Of these high-affinity interactions, IGF2R and GRN can be considered relevant networks in regulating tissue fibrosis or the microcalcification process due to their influence on T-cell activation, inflammation, wound repair, and the tissue remodelling process. The tissue cell-type enrichment indicated major expression of SORT1 in adipocytes, specialised epithelial cells, monocytes, cardiomyocytes, and thyroid glandular cells. The binding pocket analysis of human SORT1 showed twelve potential drug interaction sites with varying binding scores (0.86 to 5.83) and probability of interaction (0.004 to 0.304). Five of the drug interaction sites were observed to be targetable at the therapeutically feasible concentration of the small molecules evaluated. Empagliflozin, sitagliptin and lycopene showed a superior affinity and CA ratio compared to established inhibitors of SORT1. Conclusion: IGF2R and GRN are relevant networks of SORT1, regulating tissue fibrosis or the microcalcification process. SORT1 can be targeted using currently approved small-molecule therapeutics (empagliflozin and sitagliptin) or widely used nutraceuticals (lycopene), which should be evaluated in a randomised clinical trial to assess their efficacy in reducing the cardiac/vascular microcalcification process. Full article

Despite the therapeutical advancements in the surgical treatment of primary intra-axial neoplasms, which determined both a significative improvement in OS and QoL and a reduction in the incidence of surgery-induced major neurological deficits, nowadays patients continue to manifest subtle post-operative neurocognitive impairments, preventing them from a full reintegration back into social life and into the workforce. The birth of connectomics paved the way for a profound reappraisal of the traditional conception of brain architecture, in favour of a model based on large-scale structural and functional interactions of a complex mosaic of cortical areas organized in a fluid network interconnected by subcortical bundles. Thanks to these advancements, neurosurgery is facing a new era of connectome-based resections, in which the core principle is still represented by the achievement of an ideal onco-functional balance, but with a closer eye on whole-brain circuitry, which constitutes the foundations of both major neurological functions, to be intended as motricity; language and visuospatial function; and higher-order cognitive functions such as cognition, conation, emotion and adaptive behaviour. Indeed, the achievement of an ideal balance between the radicality of tumoral resection and the preservation, as far as possible, of the integrity of local and global brain networks stands as a mandatory goal to be fulfilled to allow patients to resume their previous life and to make neurosurgery tailored and gentler to their individual needs. Full article

The evolution of indocyanine green (ICG) fluorescence in breast and axilla surgery from an Australasian perspective is discussed in this narrative review with a focus on breast cancer and reconstruction surgery. The authors have nearly a decade of experience with ICG in a high-volume institution, which has resulted in publications and ongoing future research evaluating its use for predicting mastectomy skin flap perfusion for reconstruction, lymphatic mapping for sentinel lymph node (SLN) biopsy, and axillary reverse mapping (ARM) for prevention of lymphoedema. In the authors’ experience, routine use of ICG angiography during breast reconstruction postmastectomy was demonstrated to be cost-effective for the reduction of ischemic complications in the Australian setting. A novel tracer combination, ICG–technetium-99m offered a safe and effective substitute to the “gold standard” dual tracer for SLN biopsy, although greater costs were associated with ICG. An ongoing trial will evaluate ARM node identification using ICG fluorescence during axillary lymph node dissection and potential predictive factors of ARM node involvement. These data add to the growing literature on ICG and allow future research to build on this to improve understanding of the potential benefits of fluorescence-guided surgery in breast cancer and reconstruction surgery. Full article

Coenzyme CoQ10 (CoQ10) is an endogenous lipid-soluble antioxidant that effectively protects lipids, proteins, and DNA from oxidation due to its ability to undergo redox transitions between oxidized and reduced forms. Various oxidative stress-associated infectious and somatic diseases have been observed to disrupt the balance of CoQ10 concentration in tissues. As a high molecular weight polar lipophilic compound, CoQ10 exhibits very limited oral bioavailability, which restrains its therapeutic potential. Nevertheless, numerous studies have confirmed the clinical efficacy of CoQ10 therapy through oral administration of high doses over extended time periods. Experimental studies have demonstrated that in emergency situations, intravenous administration of both oxidized and reduced-form CoQ10 leads to a rapid increase in its concentration in organ tissues, offering protection for organ tissues in ischemic conditions. This suggests that the cardio- and neuroprotective efficacy of intravenously administered CoQ10 forms could present new opportunities in treating acute ischemic conditions. Based on these findings, the review provides reasoning supporting further research and implementation of CoQ10 dosage forms for intravenous administration in emergency situations into clinical practice. Full article

Background: Safety, efficacy, and patient comfort are the expectations during pulmonary vein isolation (PVI). We aimed to validate the combined advantages of pre- and periprocedural anticoagulation with non-vitamin K anticoagulants (NOACs) and rigorous left atrial appendage thrombus (LAAT) exclusion with computed tomography (CT). Methods: This study included a population of consecutive patients, between March 2018 and June 2020, who underwent cardiac CT within 24 h before PVI to guide the ablation and rule out LAAT. NOAC was omitted 24 h before the ablation. Results: A total of 187 patients (63% male) underwent CT before PVI. None of the patients experienced stroke during or after the procedure. The complication rate was low, with no thromboembolic events and 2.1% of patients experiencing a major bleeding event. Conclusions: Omitting NOAC 24 h before the ablation might be safe if combined with left atrial thrombus exclusion with computed tomography. Full article

Glioblastoma (GBM) is the most common and deadly primary malignant brain tumor. Current therapies are insufficient, and survival for individuals diagnosed with GBM is limited to a few months. New GBM treatments are urgent. Polymeric nanoparticles (PNs) can increase the circulation time of a drug in the brain capillaries. Polymersomes (PMs) are PNs that have been described as having attractive characteristics, mainly due to their stability, prolonged circulation period, biodegradability, their ability to sustain the release of drugs, and the possibility of surface functionalization. In this work, a poly(ethylene glycol)-ε-caprolactone (PEG-PCL) copolymer was synthesized and PMs were prepared and loaded with an hydrolytic instable compound, previously synthesized by our research team, the 3,6-bis(2,3,4,6-tetra-O-acetyl-β-glucopyranosyl)xanthone (XGAc), with promising cytotoxicity on glioblastoma cells (U-373 MG) but also on healthy cerebral endothelial cells (hCMEC/D3). The prepared PMs were spherical particles with uniform morphology and similar sizes (mean diameter of 200 nm) and were stable in aqueous suspension. The encapsulation of XGAc in PMs (80% encapsulation efficacy) protected the healthy endothelial cells from the cytotoxic effects of this compound, while maintaining cytotoxicity for the glioblastoma cell line U-373 MG. Our studies also showed that the prepared PMs can efficiently release XGAc at intratumoral pHs. Full article