Life, Volume 13, Issue 8 (August 2023) – 171 articles

Congenital cataract (CC) causes a third of the cases of treatable childhood blindness worldwide. CC is a disorder of the crystalline lens which is established as clinically divergent and has complex heterogeneity. This study aimed to determine the genetic basis of CC. Whole blood was obtained from four consanguineous families with CC. Genomic DNA was extracted from the blood, and the combination of targeted and Sanger sequencing was used to identify the causative gene. The mutations detected were analyzed in silico for structural and protein–protein interactions to predict their impact on protein activities. The sequencing found a known FYCO1 mutation (c.2206C>T; p.Gln736Term) in autosomal recessive mode in families with CC. Co-segregation analysis showed affected individuals as homozygous and carriers as heterozygous for the mutation and the unaffected as wild-type. Bioinformatics tools uncovered the loss of the Znf domain and structural compactness of the mutant protein. In conclusion, a previously reported nonsense mutation was identified in four consanguineous families with CC. Structural analysis predicted the protein as disordered and coordinated with other structural proteins. The autophagy process was found to be significant for the development of the lens and maintenance of its transparency. The identification of these markers expands the scientific knowledge of CC; the future goal should be to understand the mechanism of disease severity. Ascertaining the genetic etiology of CC in a family member facilitates establishing a molecular diagnosis, unlocks the prospect of prenatal diagnosis in pregnancies, and guides the successive generations by genetic counseling. Full article

The Sundarban is the world’s largest contiguous mangrove forest and stores around 26.62 Tg of blue carbon. The present study reviewed the factors causing a decline in its blue carbon content and poses a challenge in enhancing the carbon stock of this region. This review emphasized that recurrent tropical cyclones, soil erosion, freshwater scarcity, reduced sediment load into the delta, nutrient deficiency, salt-stress-induced changes in species composition, mangrove clearing, and anthropogenic pollution are the fundamental drivers which can potentially reduce the total blue carbon stock of this region. The southern end of the Ganges–Brahmaputra–Meghna Delta that shelters this forest has stopped its natural progradation due to inadequate sediment flow from the upper reaches. Growing population pressure from the north of the Sundarban Biosphere Reserve and severe erosion in the southern end accentuated by regional sea-level rise has left minimal options to enhance the blue carbon stock by extending the forest premises. This study collated the scholarly observations of the past decades from this region, indicating a carbon sequestration potential deterioration. By collecting the existing knowledge base, this review indicated the aspects that require immediate attention to stop this ecosystem’s draining of the valuable carbon sequestered and, at the same time, enhance the carbon stock, if possible. This review provided some key recommendations that can help sustain the blue carbon stock of the Indian Sundarban. This review stressed that characterizing the spatial variability of blue carbon with more sampling points, catering to the damaged trees after tropical cyclones, estuarine rejuvenation in the upper reaches, maintaining species diversity through afforestation programs, arresting coastal erosion through increasing sediment flow, and combating marine pollution have become urgent needs of the hour. The observations synthesized in this study can be helpful for academics, policy managers, and decision makers willing to uphold the sustainability of the blue carbon stock of this crucial ecosystem. Full article

Background: Parkinson’s disease is a progressive neurodegenerative disorder, with incidence and prevalence rates of 8–18 per 100,000 people per year and 0.3–1%, respectively. As parkinsonian symptoms do not appear until approximately 50–60% of the nigral DA-releasing neurons have been lost, the impact of routine structural imaging findings is minimal at early stages, making Parkinson’s disease an ideal condition for the application of functional imaging techniques. The aim of this multicenter study is to assess whether 123I-FP-CIT (DAT-SPECT), 123I-MIBG (mIBG-scintigraphy) or an association of both exams presents the highest diagnostic accuracy in de novo PD patients. Methods: 288 consecutive patients with suspected diagnoses of Parkinson’s disease or non- Parkinson’s disease syndromes were analyzed in the present Italian multicenter retrospective study. All subjects were de novo, drug-naive patients and met the inclusion criteria of having undergone both DAT-SPECT and mIBG-scintigraphy within one month of each other. Results: The univariate analysis including age and both mIBG-SPECT and DAT-SPECT parameters showed that the only significant values for predicting Parkinson’s disease in our population were eH/M, lH/M, ESS and LSS obtained from mIBG-scintigraphy (p < 0.001). Conclusions: mIBG-scintigraphy shows higher diagnostic accuracy in de novo Parkinson’s disease patients than DAT-SPECT, so given the superiority of the MIBG study, the combined use of both exams does not appear to be mandatory in the early phase of Parkinson’s disease. Full article

Introduction: The self-expanding, resheathable, repositionable transcatheter aortic heart valve Portico is being used successfully for transcatheter aortic valve implantation procedures (TAVI) in patients with severe aortic stenosis. The aim of this study was to evaluate outcomes at 2 years after TAVI with the Portico valve. Methods: Multicenter registry of clinical, echocardiographic and survival data from consecutive patients treated with the Portico TAVI system (Abbott, Chicago, IL, USA) in three cath labs in Northern Greece and Epirus during 2017–2020. The primary end point was all-cause mortality at 24 months. Secondary end points included procedural outcomes (efficacy and safety) and echocardiographic measurements. Results: A total of 90 patients (81 ± 6 years, 50% females, mean age 81 ± 6 years) were included in the registry. The indication for implantation was severe, symptomatic aortic stenosis (NYHA III, IV) in eighty-two (91.1%) and degeneration of a prosthetic aortic valve in eight (8.9%) patients. All patients were categorized as high surgical risk (mean Logistic Euroscore 25.9 ± 10, Euroscore II 7.7 ± 4.4 and STS score 10.8 ± 8.9). The procedure was performed transfemorally in all patients, under general anesthesia in 95.6%, under TOE guidance in 21.1%, with native valve predilatation in 46.7%, and the “resheath” option was used in 31.1% of the cases. The implantation was successful in 97.8% and there was a need for a second valve in 2.2% of the cases. Complications included permanent pacemaker implantation (16.7%), access cite complications (15.6%), arrythmias (23.3%), paravalvular leak (moderate 7.8%, severe 1.1%), acute kidney injury (7.8%), no strokes and one death during the procedure. Aortic valve peak velocity, peak and mean pressure gradients, were significantly reduced after the procedure. All-cause mortality at 1, 12 and 24 months was 4.4%, 6.7% and 7.8%, respectively. Conclusions: TAVI with the Portico system comprises an effective and safe solution for the management of severe, symptomatic aortic stenosis in high-risk surgical patients. Full article

Catheter ablation has been shown to be more effective at maintaining sinus rhythm and improving quality of life when compared to antiarrhythmic drugs. Radiofrequency and cryoablation are two effective methods. However, catheter-only ablation strategies have not consistently produced high success rates in treating longstanding and persistent AF patients. The emerging treatment of choice for such cases is hybrid ablation, which involves a multidisciplinary and minimally invasive approach to achieve surgical ablation of the direct posterior left atrial wall in combination with endocardial catheter ablation. Studies have shown promising results for the hybrid approach when compared with catheter ablation alone, but it is not without risks. Large and randomised studies are necessary to further evaluate these strategies for managing AF. Full article

Focused ultrasound (FUS) has emerged as a promising noninvasive therapeutic modality for treating atherosclerotic arterial disease. High-intensity focused ultrasound (HIFU), a noninvasive and precise modality that generates high temperatures at specific target sites within tissues, has shown promising results in reducing plaque burden and improving vascular function. While low-intensity focused ultrasound (LIFU) operates at lower energy levels, promoting mild hyperthermia and stimulating tissue repair processes. This review article provides an overview of the current state of HIFU and LIFU in treating atherosclerosis. It focuses primarily on the therapeutic potential of HIFU due to its higher penetration and ability to achieve atheroma disruption. The review summarizes findings from animal models and human trials, covering the effects of FUS on arterial plaque and arterial wall thrombolysis in carotid, coronary and peripheral arteries. This review also highlights the potential benefits of focused ultrasound, including its noninvasiveness, precise targeting, and real-time monitoring capabilities, making it an attractive approach for the treatment of atherosclerosis and emphasizes the need for further investigations to optimize FUS parameters and advance its clinical application in managing atherosclerotic arterial disease. Full article

This article relates personal recollections and starts with the origin of electron microscopy in the sixties of the previous century at the University of Amsterdam. Novel fixation and embedding techniques marked the discovery of the internal bacterial structures not visible by light microscopy. A special status became reserved for the freeze-fracture technique. By freeze-fracturing chemically fixed cells, it proved possible to examine the morphological effects of fixation. From there on, the focus switched from bacterial structure as such to their cell cycle. This invoked bacterial physiology and steady-state growth combined with electron microscopy. Electron-microscopic autoradiography with pulses of [³H] Dap revealed that segregation of replicating DNA cannot proceed according to a model of zonal growth (with envelope-attached DNA). This stimulated us to further investigate the sacculus, the peptidoglycan macromolecule. In particular, we focused on the involvement of penicillin-binding proteins such as PBP2 and PBP3, and their role in division. Adding aztreonam (an inhibitor of PBP3) blocked ongoing divisions but not the initiation of new ones. A PBP3-independent peptidoglycan synthesis (PIPS) appeared to precede a PBP3-dependent step. The possible chemical nature of PIPS is discussed. Full article

(1) Objective: Keloid and hypertrophic scars are a challenge in clinical management, causing functional and psychological discomfort. These pathological scars are caused by a proliferation of dermal tissue following skin injury. The TGF-β/Smad signal pathway in the fibroblasts and myofibroblasts is involved in the scarring process of skin fibrosis. Today, multiple therapeutic strategies that target the TGF-β/Smad signal pathway are evaluated to attenuate aberrant skin scars that are sometimes difficult to manage. We performed a head-to-head, randomized controlled trial evaluating the appearance of the post-surgical scars of 64 subjects after two times daily topical application to compare the effect of a class I pullulan-based medical device containing Allium cepa extract 5% and hyaluronic acid 5% gel versus a class I medical device silicone gel on new post-surgical wounds. (2) Methods: Objective scar assessment using the Vancouver Scar Scale (VSS), POSAS, and other scales were performed after 4, 8, and 12 weeks of treatment and statistical analyses were performed. The trial was registered in clinicalTrials.gov ( NCT05412745). In parallel, molecular docking simulations have been performed to investigate the role of Allium cepa in TGF-β/Smad signal pathway. (3) Results: We showed that VSS, POSAS scale, itching, and redness reduced significantly at week 4 and 8 in the subjects using devices containing Allium cepa and HA. No statistically significant differences in evaluated scores were noted at 12 weeks of treatment. Safety was also evaluated by gathering adverse events related to the application of the gel. Subject compliance and safety with the assigned gel were similar between the two study groups. Molecular docking simulations have shown how Allium cepa could inhibit fibroblasts proliferation and contraction via TGF-β/Smad signal pathway. (4) Conclusions: The topical application of a pullulan-based medical device containing Allium cepa and HA showed a clear reduction in the local inflammation, which might lead to a reduced probability of developing hypertrophic scars or keloids. Full article

Pulicaria jaubertii (PJ) is a medicinal plant used as a synthetic antioxidant and as a traditional medicine due to its bioactive compounds. The objective of this study was to investigate the effects of PJ on carcass traits and breast meat quality parameters of broiler chickens. Two hundred and forty male broilers (1 day old) were divided into four groups (0, 3, 6, and 9 g of PJ/kg of basal diet). Performance indicators were evaluated during the feeding stages, and carcass characteristics and physiochemical and qualitative parameters of breast meat were measured at 36 days old. The results showed that PJ improved performance parameters such as weight gain, feed conversion ratio, and production efficiency index (p < 0.05) in the finishing stage. The diets supplemented with PJ were associated with better carcass characteristics (p < 0.05), but some body parts, such as legs (6 and 9 g PJ) and backs (3–9 g PJ) decreased (p < 0.05). Temperature and initial pH were decreased by PJ (p < 0.05). Meat color was not affected by PJ (p > 0.05), although the yellowness and saturation index were lower at 9 g PJ. Total saturated fatty acid content was higher at 3 g PJ, while total polyunsaturated fatty acids and unsaturated to saturated fatty acid ratio were lower at 3 and 6 g PJ (p < 0.05). Total monounsaturated fatty acid content increased at 6 and 9 g PJ. Omega-6 fatty acids and the ratio of omega-6 to omega-3 were lower at 3 g PJ. PJ resulted in higher weight loss on cooking (6 and 9 g PJ) and shear force (3–9 g PJ). In conclusion, PJ had a positive influence on performance, carcass characteristics, and fatty acid profile, and some meat quality traits were generally improved by PJ, but knowledge of its mode of action is still limited and therefore requires further investigation. Full article

TNF-α inhibitors (TNFis) have revolutionized the treatment of certain chronic immune-mediated diseases, being widely and successfully used in rheumatic inflammatory diseases, and have also proved their efficacy in the treatment of inflammatory bowel disease (IBD). However, among the side effects of these agents are the so-called paradoxical effects. They can be defined as the appearance or exacerbation of a pathological condition that usually responds to this class of drug while treating a patient for another condition. A wide range of paradoxical effects have been reported including dermatological, intestinal and ophthalmic conditions. The causal mechanism of occurrence may implicate an imbalance of cytokines, but is still not fully understood, and remains a matter of debate. These paradoxical reactions often show improvement on discontinuation of the medication or on switching to another TNFi, but in some cases it is a class effect that could lead to the withdrawal of all anti-TNF agents. Close monitoring of patients treated with TNFis is necessary in order to detect paradoxical reactions. In this study we focus on reviewing IBD occurrence as a paradoxical effect of TNFi therapy in patients with rheumatological diseases (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and juvenile idiopathic arthritis). Full article

Sodium–glucose cotransporter-2 inhibitors (SGLT2is) are a relatively new class of antidiabetic drugs that have shown favorable effects in heart failure (HF) patients, irrespective of the left ventricular ejection fraction (LVEF). Recent studies have demonstrated the beneficial effects of empagliflozin on cardiac function and structure; however, less is known about dapagliflozin. The purpose of the current work was to investigate the association between the use of dapagliflozin and cardiac biomarkers as well as the cardiac structure in a cohort of patients with HF and diabetes mellitus (DM). The present work was an observational study that included 118 patients (dapagliflozin group n = 60; control group n = 58) with HF and DM. The inclusion criteria included: age > 18 years, a history of DM and HF, regardless of LVEF, and hospitalization for HF exacerbation within the previous 6 months. The exclusion criteria were previous treatment with SGLT2i or glucagon-like peptide-1 receptor agonists, a GFR< 30 and life expectancy < 1 year. The evaluation of patients (at baseline, 6 and 12 months) included a clinical assessment, laboratory blood tests and echocardiography. The Mann–Whitney test was used for the comparison of continuous variables between the two groups, while Friedman’s analysis of variance for repeated measures was used for the comparison of continuous variables. Troponin (p < 0.001) and brain natriuretic peptide (BNP) (p < 0.001) decreased significantly throughout the follow-up period in the dapagliflozin group, but not in the control group (p > 0.05 for both). The LV end-diastolic volume index (p < 0.001 for both groups) and LV end-systolic volume index (p < 0.001 for both groups) decreased significantly in the dapagliflozin and the control group, respectively. The LVEF increased significantly (p < 0.001) only in the dapagliflozin group, whereas the global longitudinal strain (GLS) improved in the dapagliflozin group (p < 0.001) and was impaired in the control group (p = 0.021). The left atrial volume index decreased in the dapagliflozin group (p < 0.001) but remained unchanged in the control group (p = 0.114). Lastly, the left ventricular mass index increased significantly both in the dapagliflozin (p = 0.003) and control group (p = 0.001). Dapagliflozin, an SGLT2i, was associated with a reduction in cardiac biomarkers and with reverse cardiac remodeling in patients with HF and DM. Full article

Background: The purpose of this study was to objectively evaluate visual discomfort using an eye tracker and aberrometer after a 21-min reading session on an iPad and an Ebook. Additionally, retinal changes were analyzed using optical coherence tomography (OCT). Methods: A total of 31 young subjects (24 ± 4 years) participated in this study. They read for 21 min on an Ebook and for another 21 min on an iPad under controlled lighting conditions while their eye movements were monitored using an eye tracker. Aberrometry and retinal OCT measurements were taken before and after each reading session. Parameters such as pupil diameter, fixations, saccades, blinks, total aberration, high-order aberration, low-order aberration, and central and peripheral retinal thickness in the nine early treatment diabetic retinopathy study (ETDRS) areas were measured for each reading situation. Statistical analysis was performed on the collected data. Results: No statistically significant differences (p > 0.05) between the two devices were observed in terms of the different types of eye movements or the changes in retinal thickness. However, the aberrometric analysis showed variations in post-reading situations depending on the device used. Conclusion: Reading speed and visual discomfort resulting from electronic device usage can be objectively assessed using an eye tracker and aberrometer. Additionally, changes found in central and peripheral retinal thickness between the two devices and the baseline measurements were not significant and remained relatively stable. Full article

Motoneurons receive thousands of excitatory and inhibitory synapses from descending tracts and primary afferent fibers. The excitability of these neurons must be precisely regulated to respond adequately to the requirements of the environment. In this context, GABA_A and GABA_B receptors regulate motoneuron synaptic strength. GABA_A and GABA_B receptors are expressed on primary afferent fibers and motoneurons, while in the descending afferent fibers, only the GABA_B receptors are expressed. However, it remains to be known where the GABA that activates them comes from since the GABAergic interneurons that make axo-axonic contacts with primary afferents have yet to be identified in the descending afferent terminals. Thus, the main aim of the present report was to investigate how GABA_B receptors functionally modulate synaptic strength between Ia afferent fibers, excitatory and inhibitory descending fibers of the dorsolateral funiculus, and spinal motoneurons. Using intracellular recordings from the spinal cord of the turtle, we provide evidence that the GABA_B receptor antagonist, CGP55845, not only prevents baclofen-induced depression of EPSPs but also increases motoneuron excitability and enhances the synaptic strength between the afferent fibers and motoneurons. The last action of CGP55845 was similar in excitatory and inhibitory descending afferents. Interestingly, the action of baclofen was more intense in the Ia primary afferents than in the descending afferents. Even more, CGP55845 reversed the EPSP depression induced by the increased concentration of ambient GABA produced by interneuron activation and GABA transporter blockade. Immunofluorescence data corroborated the expression of GABA_B receptors in the turtle’s spinal cord. These findings suggest that GABA_B receptors are extrasynaptic and tonically activated on descending afferent fibers and motoneurons by GABA released from astrocytes and GABAergic interneurons in the cellular microenvironment. Finally, our results also suggest that the antispastic action of baclofen may be due to reduced synaptic strength between descending fibers and motoneurons. Full article

The aim of this study was to evaluate the endocervical margin status according to transformation zone (TZ) and high-risk HPV (hr-HPV) subtype in specimens with cone length ≤ 10 mm versus > 10 mm to provide data for informed decision making and patients counseling especially for women wishing to conceive. In this retrospective cohort study, 854 patients who underwent large loop excision of the transformation zone during a nine-year period (2013–2021) for cervical disease were analyzed. The main outcome parameters were excision length, histological result, TZ type, HPV subtype and endocervical margin status. A subgroup analysis was performed according to excision length, with a cut-off value of 10 mm. A two-step surgical procedure was performed in case of an excision length of > 10 mm. The overall rate of positive endocervical margins irrespective of excision length was 17.2%, with 19.3% in specimens with ≤ 10 mm and 15.0% with > 10 mm excision length. Overall, 41.2% of women with a visible TZ and HPV 16/hr infection and 27.0% of women with HPV 18 received an excisional treatment of > 10 mm length without further oncological benefit, respectively. In contrast, assuming that only an excision of ≤ 10 mm length had been performed in women with visible TZ, the rate of clear endocervical margins would have been 63.7% for HPV 16/hr infections and 49.3% for HPV 18 infections. In conclusion, the decision about excision length should be discussed with the patient in terms of oncological safety and the risk of adverse pregnancy events. An excision length > 10 mm increases the number of cases with cervical tissue removed without further oncological benefit, which needs to be taken into account in order to provide an individual therapeutic approach. Furthermore, HPV 18 positivity is related to a higher rate of positive endocervical margins irrespective of TZ. Full article

Background: Placenta accreta spectrum (PAS) is a clinical entity significantly increasing the risk of a peripartum hemorrhage. Various surgical methods have been described in the literature, which aim to reduce the risk of bleeding, although they often lack reproducibility and have been performed on low numbers of patients. The aim of this study was to evaluate the use of the Foley catheter as a cervical tourniquet during cesarean sections, in patients with PAS. Methods: All patients who underwent peripartum hysterectomy due to PAS in a large single-center registry were included in the present analysis. The general demographics and clinical characteristics of all participants, including blood loss, and maternal and fetal outcomes, were collected and analyzed. Results: Twelve participants were included. The mean blood loss was 1200 ± 760 ml during operation and the mean ± SD procedural duration was 89 ± 17 min. The median (Q1–Q3) length of hospital stay post-procedurally was 5 (4–6) days. None of the patients required subsequent urgent surgical procedures after hysterectomy. The median (Q1–Q3) packed red blood cell units transfused in our cohort was 2 (0–3). Conclusion: Using the Foley catheter as a tourniquet might be an effective method of excessive bleeding prevention in patients with PAS during peripartum hysterectomy. Full article

Objective: The aim of this investigation was to compare the thickness of the deep local muscles in the neck region, as well as local and widespread sensitivity and functionality, between individuals with migraine and healthy control subjects. Methods: An observational study was carried out in accordance with the STROBE statements. The flexor longus colli and multifidus, two neck-stabilizing muscles, were measured using B-mode ultrasound imaging. The upper trapezius, masseter, temporalis, anterior tibialis, and median nerve all underwent bilateral pressure-pain threshold (PPT) assessments. The statistical program SPSS 29.0 was used to implement the Mann–Whitney U test and Chi-squared test. Spearman Rho was utilized to establish the correlations between the variables. Results: Sixty participants were enrolled in the study. The subjects, who were matched in terms of age, gender, and body mass index (BMI), were equally divided into migraine and control groups. No significant differences between the groups were found in the multifidus CSA regarding both sides at rest (right: p = 0.625; left: p = 0.203). However, in contraction, the multifidus CSA showed a significant decrease on the left side in the patients with migraine compared to the controls (p = 0.032), but no significant differences were found in the right multifidus CSA in contraction between the two groups (p = 0.270). In comparison to the healthy volunteers, the migraine sufferers showed a substantial reduction in CSA in the longus colli muscle on both the left side (p = 0.001) and the right side at rest (p = 0.003), as well as in the CSA of the left longus colli in contraction (p < 0.001). Furthermore, the migraine patients showed significantly lower PPT compared to the healthy subjects in local and widespread areas bilaterally. All the parameters revealed higher sensitization in the migraine group in the following areas: the right and left temporal regions (p < 0.001), the right and left upper trapezius (p < 0.001 and p < 0.01, respectively), the right and left masseter muscles (p < 0.01), the right and left median nerves (p < 0.001 and p < 0.01, respectively), and the right and left anterior tibialis muscles (p < 0.001). In terms of the craniocervical flexion test (CCFT), the migraine patients demonstrated significantly lower values than the healthy subjects (p < 0.001). A moderate positive correlation was noted between the PPT in the right temporalis muscle and that in the left longus colli and the right multifidus in contraction. The PPT in the right temporalis muscle also exhibited a positive correlation with the CCFT, although this correlation was low. Between the PPT values, the upper trapezius on both sides showed a moderate positive correlation with the median nerve bilaterally. Conclusions: This research suggests that individuals with migraine may experience local and widespread pain sensitization. A decrease in functionality due to the low muscle endurance of the deep cervical muscles is also accompanied by low values of muscle thickness in contraction. These findings may help to select more accurate treatment approaches for patients with migraine. Full article

Serum adiponectin plays a vital role in various physiological processes, such as anti-inflammatory, anti-atherosclerotic, anti-apoptotic and pro-angiogenic activities. Any abnormalities in its concentration can lead to adverse health outcomes, particularly in children and adolescents. Therefore, it is crucial to investigate factors influencing serum adiponectin concentrations in this population. The primary objective of this study was to systematically evaluate the impact of aerobic exercise on serum adiponectin concentrations in children and adolescents with obesity. To achieve this, a comprehensive literature search was conducted up to January 2023, utilising five databases: PubMed, Web of Science, Embase, Cochrane Library and Clinicaltrial.gov. The inclusion criteria involved studies that focused solely on aerobic exercise as an intervention for children and adolescents with obesity. Only studies that reported outcome indicators related to serum adiponectin were considered for analysis. The quality of the included studies was assessed using the Cochrane Risk of Bias (ROB) assessment tool, and statistical analysis was performed using RevMan 5.4.1 analysis software. This meta-analysis incorporated data from eight trials, involving a total of 272 subjects. The results demonstrated that aerobic training significantly increased serum adiponectin concentrations [standardized mean difference (SMD) = 0.85; 95% confidence interval (CI) = 0.33 to 1.37; I² = 0%; p = 0.001] in children and adolescents with obesity when compared to non-exercise controls. Furthermore, the magnitude of this effect appears to be influenced by the intensity of aerobic exercise, with higher-intensity aerobic exercise resulting in greater increases in serum adiponectin concentrations. Full article

(1) Background: Cerebrospinal fluid (CSF) leakage is one of the most common complications of microvascular decompression (MVD) surgery. Before fatal complications, such as intracranial infection, occur, early recognition and prompt treatment are essential. (2) Methods: The clinical data of 475 patients who underwent MVD surgery from September 2020 to March 2023 were retrospectively analyzed. In these patients, if there were any symptoms of CSF leakage, and if CSF leakage was evident, a lumbar drainage catheter was inserted immediately. (3) Results: CSF leakage was suspected in 18 (3.8%) patients. Five of these patients (1.1%) showed signs of CSF leakage during conservative management and subsequently underwent catheter insertion for lumbar drainage. The lumbar drain was removed after an average of 5.2 days, resulting in an average hospitalization of 14.8 days. In all 5 patients, CSF leakage was resolved without reoperation. (4) Conclusions: Our treatment strategy prevented the development of fatal complications. Close observation of the symptoms and postoperative temporal bone computed tomography and audiometry are considered to be good evaluation methods for all patients. If CSF leakage is certain, it is important to perform lumbar drainage immediately. Full article

Introduction: Takotsubo cardiomyopathy (TCM) is a reversible form of cardiomyopathy characterized by transient regional systolic dysfunction of the left ventricle. Case outline: A 78-year-old woman was admitted to the general hospital due to acute inferior STEMI late presentation. Two days after admission, the patient reported intense chest pain and an ECG registered diffuse ST-segment elevation in all leads with ST-segment denivelation in aVR. The patient also showed clinical signs of cardiogenic shock and was referred to a reference institution for further evaluation. Echocardiography revealed akinesia of all medioapical segments, dynamic obstruction of the left ventricular outflow tract (LVOT), moderate mitral regurgitation, and pericardial effusion. Coronary angiography showed the suboccluded right coronary artery, and a primary percutaneous coronary intervention was performed, which involved implanting a drug-eluting stent. The patient’s condition worsened as pericardial effusion increased and led to tamponade. Pericardiocentesis was performed, resulting in the patient’s stabilization. At this point, significant gradients at the LVOT and pericardial effusion were not registered. After eight days without symptoms and stable status, the patient was discharged. Conclusions: The simultaneous presence of AMI and TCM increases the risk of developing cardiogenic shock. The cardio-circulatory profile of these patients is different from those with AMI. Full article

Gastric cancer is a significant health concern worldwide, and lymphadenectomy plays a crucial role in its treatment. However, there is ongoing debate regarding the optimal approach—D1 or D2 lymphadenectomy. This paper aims to synthesize the available evidence by conducting a comprehensive literature review and comparing the advantages and disadvantages of both techniques. The analysis includes studies, clinical trials, and systematic reviews that assess survival outcomes, morbidity, and quality of life. The selected studies revealed different outcomes associated with D1 and D2 lymphadenectomy, including lymph node harvest, disease control, recurrence rates, and overall survival. Postoperative complications also varied between the two techniques. These findings highlight the complex considerations involved in selecting the most suitable lymphadenectomy approach for individual patients. Therefore, the decision requires an individualized assessment that considers the potential benefits and risks of D1 and D2 techniques. A collaborative approach involving interdisciplinary teams is crucial for developing personalized treatment plans that optimize both oncological outcomes and postoperative quality of life. Full article

Background: Trail running socks with the same fibers and design but with different separations of their three-dimensional waves could have different thermoregulatory effects. Therefore, the objective of this study was to evaluate the temperatures reflected on the sole of the foot after a mountain race with the use of two models of socks with different wave separations. Material and Methods: In a sample of 34 subjects (twenty-seven men and seven women), the plantar temperature was analyzed with the thermal imaging camera Flir E60bx^® (Flir systems, Wilsonville, OR, USA) before and after running 14 km in mountainous terrain at a hot temperature of 27 °C. Each group of 17 runners ran with a different model of separation between the waves of the tissue (2 mm versus 1 mm). After conducting the post-exercise thermographic analysis, a Likert-type survey was conducted to evaluate the physiological characteristics of both types of socks. Results: There was a significant increase in temperature in all areas of interest (p < 0.001) after a 14 km running distance with the two models of socks. The hallux zone increased in temperature the most after the race, with temperatures of 8.19 ± 3.1 °C and 7.46 ± 2.1 °C for the AWC 2.2 and AWC 3, respectively. However, no significant differences in temperature increases were found in any of the areas analyzed between the two groups. Runners perceived significant differences in thermal sensation between AWC 2.2 socks with 4.41 ± 0.62 points and AWC 3 with 3.76 ± 1.03 points (p = 0.034). Conclusion: Both models had a similar thermoregulatory effect on the soles of the feet, so they can be used interchangeably in short-distance mountain races. The perceived sensation of increased thermal comfort does not correspond to the temperature data. Full article

Background: Hantaviruses remain an important case of emerging and re-emerging infections in human medicine. This study aimed to analyse the epidemiology, clinical presentation, and outcome of hantavirus infections in the western part of Republic of Croatia, a new geographical area for hantavirus infections. Methods: Retrospective analysis of medical records of patients treated for hemorrhagic fever with renal syndrome (HFRS) at the infectious diseases Clinic of the Clinical Hospital Center in Rijeka, Croatia, from 1 January 2014, to 31 December 2021. Results: During the eight-year period, 251 patients were hospitalized and treated for HFRS, with epidemic outbreaks in years 2014 and 2021. Most patients had a typical clinical course of HFRS and received supportive care. Serological analysis revealed the Puumala Virus (PUUV) as the predominant etiology of the disease. Epidemiological analysis revealed clustering of infections in the region of Gorski Kotar and spread to the area on the Mediterranean coast (Adriatic Sea), which was previously considered an area free from hantavirus infections. Conclusions: The presented results indicate the spread of hantavirus infections in Croatia from the central low-lying parts of the country to the tourist-attractive western area adjacent to the Mediterranean coast, which was previously considered free of hantavirus infections. Full article

Background: Haemorrhagic stroke, accounting for 10–20% of all strokes, often requires decompressive surgery as a life-saving measure for cases with massive oedema and raised intracranial pressure. This study was conducted to compare the demographics, characteristics and rehabilitation profiles of patients with severe haemorrhagic stroke who were managed surgically versus those who were managed non-surgically. Methods: A single-centre retrospective study of electronic medical records was conducted over a 3-year period from 1 January 2018 to 31 December 2020. The inclusion criteria were first haemorrhagic stroke, age of >18 years and an admission Functional Independence Measure (FIM™) score of 18–40 upon admission to the rehabilitation centre. The primary outcome measure was discharge FIM™. Secondary outcome measures included modified Rankin Scale (mRS), rehabilitation length of stay (RLOS) and complication rates. Results: A total of 107 patients’ records were analysed; 45 (42.1%) received surgical intervention and 62 (57.9%) patients underwent non-surgical management. Surgically managed patients were significantly younger than non-surgical patients, with a mean age of [surgical 53.1 (SD 12) vs. non-surgical 61.6 (SD 12.3), p = 0.001]. Admission FIM was significantly lower in the surgical vs. non-surgical group [23.7 (SD6.7) vs. 26.71 (SD 7.4), p = 0.031). However, discharge FIM was similar between both groups [surgical 53.91 (SD23.0) vs. non-surgical 57.0 (SD23.6), p = 0.625). Similarly, FIM gain (surgical 30.1 (SD 21.1) vs. non-surgical 30.3 (SD 21.1), p = 0.094) and RLOS [surgical 56.2 days (SD 21.5) vs. non-surgical 52.0 days (SD 23.4), p = 0.134) were not significantly different between groups. The majority of patients were discharged home (surgical 73.3% vs. non-surgical 74.2%, p = 0.920) despite a high level of dependency. Conclusions: Our findings suggest that patients with surgically managed haemorrhagic stroke, while older and more dependent on admission to rehabilitation, achieved comparable FIM gains, discharge FIM and discharge home rates after ~8 weeks of rehabilitation. This highlights the importance of rehabilitation, especially for surgically managed haemorrhagic stroke patients. Full article

The microbiota inhabits the gastrointestinal tract, providing essential capacities to the host. The microbiota is a crucial factor in intestinal health and regulates intestinal physiology. However, microbiota disturbances, named dysbiosis, can disrupt intestinal homeostasis, leading to the development of diseases. Classically, the microbiota has been referred to as bacteria, though other organisms form this complex group, including viruses, archaea, and eukaryotes such as fungi and protozoa. This review aims to clarify the role of helminths, bacteriophages, fungi, and archaea in intestinal homeostasis and diseases, their interaction with bacteria, and their use as therapeutic targets in intestinal maladies. Full article

(1) Background: The influence of the menstrual cycle on physical fitness in athletes is controversial in the scientific literature. There is a marked fluctuation of sex hormones at three key points of the menstrual cycle, where estrogen and progesterone vary significantly. Hormonal contraception induces hormonal levels different from the natural menstrual cycle, requiring specific study in relation to physical fitness. (2) Method: Women aged 18 to 40 years with regular natural menstrual cycles and women using hormonal contraception were recruited, creating two study groups. All participants needed to be athletes classified as level II–III, based on training volume/physical activity metrics, among other variables. To assess their physical fitness, cardiorespiratory fitness (measured by $\dot{\mathrm{V}}$O₂max), high-speed strength, hand grip strength, and flexibility were evaluated. Blood samples were taken to determine the menstrual cycle phase through analysis of sex hormone levels. Additionally, urine tests for ovulation detection were performed for the natural menstrual cycle group. Neurosensory stimulation tests were incorporated to measure sensory thresholds and pain thresholds in each phase. Body composition in each phase and its relationship with the other variables were also taken into account. (3) Results: Athletes in the natural cycling group showed differences in $\dot{\mathrm{V}}$O₂max (mL·kg⁻¹·min⁻¹) (phase I = 41.75 vs. phase II = 43.85 and (p = 0.004) and phase I vs. phase III = 43.25 mL·kg⁻¹·min⁻¹ (p = 0.043)), as well as in body weight (phase I = 63.23 vs. phase III = 62.48 kg; p = 0.006), first pain threshold (phase I = 1.34 vs. phase II = 1.69 (p = 0.027) and phase III = 1.59 mA (p = 0.011)), and sensitive threshold (phase I = 0.64 vs. phase II = 0.76 mA (p = 0.017)). The pain threshold was found to be an important covariate in relation to $\dot{\mathrm{V}}$O₂max, explaining 31.9% of the variance in phase I (p = 0.006). These findings were not observed between the two phases of contraceptive cycling. (4) Conclusion: The natural menstrual cycle will cause significant changes in the physical fitness of athletes. The use of hormonal contraception is not innocuous. Women with natural cycles show an increase in cardiorespiratory fitness in phases II and III, which is a factor to be considered in relation to training level and workload. Full article

Background: The minimum clinically important difference (MCID) for the St George’s Respiratory Questionnaire (SGRQ) is debated in chronic obstructive pulmonary disease (COPD) quality-of-life (QoL) assessments. This study aimed to determine whether there is a difference in predictors of clinically significant improvement between the traditional (value of 4) and newly proposed MCID SGRQ (value of 7) after climatic rehabilitation treatment. Climatic rehabilitation treatment consists of two main parts: climatotherapy, which typically involves the controlled exposure of individuals to natural environmental elements, and climatic rehabilitation, which includes other therapeutic factors such as physical activities as well as educating the patient to change their lifestyle. Methods: This study included 90 consecutive patients diagnosed with COPD who underwent structured complex pulmonary rehabilitation in High Tatras, part of the Carpathian Mountains. The examination before and after treatment included spirometry, QoL assessment using the SGRQ, 6 min walk test (6-MWT), and the Borg, Beck and Zung scale. Results: Patients showed statistically significant improvement after the intervention in FEV1, FEV1/FVC, 6-MWT, (p < 0.001), anxiety scores, depression, and improvement in dyspnoea both before and after the 6-MWT (p < 0.001). For both MCID for SGRQ levels 4 and 7, we confirmed the same predictors of clinical improvement for bronchial obstruction grade (spirometry) and exercise capacity (6-MWT), for quality of life in activity score and total score. Conclusion. The results suggest that both the proposed MCID for SGRQ values could be sufficient to assess the clinical significance of the achieved change in health status when assessing the need for pulmonary rehabilitation comprising climatotherapy in patients with COPD. Full article

Proximal hamstring tears are among the most common injuries afflicting athletes and middle-aged individuals. Sciatic nerve compression after a proximal hamstring injury, which can occur due to scar formation and subsequent irritation or compression of the nerve, is an infrequent but severe complication with few cases documented in the literature. No evidence is available about the optimal treatment for sciatic nerve symptoms after proximal hamstring injuries. In this case report, we present two cases involving patients primarily treated conservatively at another institution after suffering from a proximal hamstring injury and developing sciatic nerve symptoms over the course of a few months. Both were treated with open neurolysis at our institution without reattachment of the ruptured muscles to the ischial tuberosity due to the chronicity of the injuries. Both patients exhibited neurological symptoms over two years, which recovered after surgery. These two cases show that neurolysis of the sciatic nerve without reattachment of the proximal hamstring muscles is an applicable option for the treatment of chronic proximal hamstring tears with sciatic nerve compression. Further studies will be needed to validate this hypothesis. Full article

Viral hepatitis continues to be the leading cause of morbidity and mortality worldwide, but the burden has significantly diminished thanks to the large-scale use of vaccines and antivirals. However, there are still challenges regarding viral hepatitis management, especially when more than one pathogenic agent is involved. We present the case of a 45-year-old woman who had a simultaneous infection involving three hepatitis viruses: HAV, HBV, and HEV. Full article

Hemifacial spasm is typically caused by contact between the facial nerve and blood vessels. Microvascular decompression, a treatment that directly addresses this pathogenesis, is often considered the most effective treatment method. However, surgery is not immediately performed for patients at risk from the surgical treatment, or for those with an unclear diagnosis. In these instances, Botulinum toxin injection can help manage the patient’s symptoms. Numerous studies corroborate the effectiveness and safety of Botulinum toxin treatment, with large-scale studies indicating symptom control lasts, on average, around 15 weeks. Full article

Background and Aim: Ultrasound (US) imaging is increasingly preferred over other more invasive modalities in preclinical studies using animal models. However, this technique has some limitations, mainly related to operator dependence. To overcome some of the current drawbacks, sophisticated data processing models are proposed, in particular artificial intelligence models based on deep learning (DL) networks. This systematic review aims to overview the application of DL algorithms in assisting US analysis of images acquired in in vivo preclinical studies on animal models. Methods: A literature search was conducted using the Scopus and PubMed databases. Studies published from January 2012 to November 2022 that developed DL models on US images acquired in preclinical/animal experimental scenarios were eligible for inclusion. This review was conducted according to PRISMA guidelines. Results: Fifty-six studies were enrolled and classified into five groups based on the anatomical district in which the DL models were used. Sixteen studies focused on the cardiovascular system and fourteen on the abdominal organs. Five studies applied DL networks to images of the musculoskeletal system and eight investigations involved the brain. Thirteen papers, grouped under a miscellaneous category, proposed heterogeneous applications adopting DL systems. Our analysis also highlighted that murine models were the most common animals used in in vivo studies applying DL to US imaging. Conclusion: DL techniques show great potential in terms of US images acquired in preclinical studies using animal models. However, in this scenario, these techniques are still in their early stages, and there is room for improvement, such as sample sizes, data preprocessing, and model interpretability. Full article