Search Results (705)

Refractory full-thickness macular holes (rFTMHs) present a significant challenge in vitreoretinal surgery, with reported incidence rates of 4.2–11.2% following standard vitrectomy with internal limiting membrane (ILM) peeling and gas tamponade. Risk factors include large hole size (>400 µm), chronicity (>6 months), high myopia, incomplete ILM peeling, and post-operative noncompliance. Multiple surgical techniques exist, though comparative evidence remains limited. Current options include the inverted ILM flap technique, autologous ILM transplantation (free flap or plug), lens capsular flap transplantation (autologous or allogenic), preserved human amniotic membrane transplantation, macular subretinal fluid injection, macular fibrin plug with autologous platelet concentrates, and autologous retinal transplantation. Closure rates range from 57.1% to 100%, with selection depending on hole size, residual ILM, patient posturing ability, etc. For non-posturing patients, fibrin plugs are preferred. Residual ILM cases may benefit from extended peeling or flap techniques, while large holes often require scaffold-based (lens capsule, amniotic membrane) or fibrin plug approaches. Pseudophakic patients should avoid posterior capsular flaps due to lower success rates. Despite promising outcomes, the lack of randomized trials necessitates further research to establish evidence-based guidelines. Personalized surgical planning, considering anatomical and functional goals, remains crucial in optimizing visual recovery in rFTMHs. Full article

Projections indicate that the global urban population is anticipated to reach 67.2% by 2050, accompanied by a threefold increase in urban built-up areas worldwide. Urbanization has profoundly transformed Earth’s natural environment, notably characterized by the drastic reduction and fragmentation of wildlife habitats. These changes contribute to local species extinction, leading to biodiversity loss and profoundly impacting ecological processes and regional sustainable development. However, within urban settings, certain ‘generalist’ species demonstrate survival capabilities contingent upon phenotypic plasticity. The co-evolution of gut microbiota with their hosts emerges as a key driver of this phenotypic plasticity. The presence of diverse gut microbiota constitutes a crucial adaptive mechanism essential for enabling hosts to adjust to rapid environmental shifts. This review comprehensively explores amniote gut microbial changes in the context of urbanization, examining potential drivers of these changes (including diet and environmental pollutants) and their potential consequences for host health (such as physiology, metabolism, immune function, and susceptibility to infectious and non-infectious diseases). Ultimately, the implications of the gut microbiome are highlighted for elucidating key issues in ecology and evolution. This understanding is expected to enhance our comprehension of species adaptation in the Anthropocene. Full article

Understanding protein and amino acid deposition in pregnant gilts is important for developing nutritional strategies that meet these demands and enhance reproductive performance. Current models, such as the NRC (2012) gestating sow model, assume a constant proportional protein and amino acid content in tissues throughout pregnancy. However, empirical data suggest that gestational tissue growth and composition change dynamically. In this study, we developed a gestation model that characterizes the dynamic changes in growth, crude protein, and amino acid deposition throughout gestation. Based on a systematized search of published data, mathematical functions were developed to estimate daily protein and amino acid deposition in key tissues, including allantoic and amniotic fluid, uterus, placenta, fetus, mammary gland, and maternal body. Our results suggest that dietary crude protein levels and amino acid profiles should be adjusted to meet metabolic demands, particularly in early gestation, where a potential nutritional deficiency was identified. Additionally, the amino acid profile of deposited protein shifts during late gestation, suggesting a changing demand for specific amino acids. These findings challenge existing models and highlight the need for adaptive dietary strategies that better align with pregnancy’s biological demands. By refining protein and amino acid deposition estimates, this study provides a framework guiding future research on precision feeding, ultimately improving gilt and sow reproductive performance. Full article

Background: Histologic chorioamnionitis (HCA) is a placental inflammatory condition characterized by neutrophilic infiltration of the fetal membranes, often occurring without overt clinical signs or symptoms. Risk factors include prolonged labor, premature rupture of membranes (PROM) exceeding 12 h, nulliparity, labor dystocia, and lower socioeconomic status. Although HCA frequently presents as a subclinical condition, its early diagnosis remains challenging. Nevertheless, HCA is associated with an increased risk of maternal and neonatal morbidity, including early-onset neonatal sepsis, cerebral palsy, and long-term neurodevelopmental impairment. We report the case of a 29-year-old primigravida at 40 + 0 weeks of gestation, admitted for decreased fetal movements. Discussion: Cardiotocographic (CTG) monitoring revealed a “zigzag pattern” in the absence of maternal fever, leukocytosis, or tachycardia. Due to the CTG findings suggestive of possible fetal compromise, in addition to reduced fetal movements, an emergency cesarean section was performed. Intraoperative findings included heavily meconium-stained amniotic fluid, then the examination of the placenta confirmed acute HCA with a maternal inflammatory response, without evidence of fetal inflammatory response. Conclusion: This case highlights the crucial role of CTG abnormalities, particularly the “zigzag pattern,” as an early marker of subclinical intrauterine inflammation. Early recognition of such patterns may facilitate timely intervention and improve perinatal outcomes in cases of histologic chorioamnionitis. Full article

This study aimed to comprehensively review surgical interventions for ocular surface diseases (OSDs), including dry eye syndrome (DES), exposure keratopathy, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and ocular graft versus host disease (oGVHD), and to highlight the indications, contraindications, outcomes, and complications of various oculoplastic procedures used in their management. A narrative review was performed based on expert-guided selection of relevant studies retrieved from PubMed, Scopus, and Web of Science. Relevant keywords included “ocular surface disease”, “dry eye syndrome”, “exposure keratopathy”, “thyroid eye disease (TED)”, “neurotrophic keratopathy (NK)”, “Stevens-Johnson syndrome”, “toxic epidermal necrolysis”, “punctal occlusion”, “tarsorrhaphy”, “botulinum toxin”, “eyelid loading”, “retractor weakening”, “corneal neurotization (CN)”, “amniotic membrane transplantation (AMT)”, “conjunctival flap”, “ocular graft versus host disease”, and “salivary gland transplantation (SGT)”. Studies addressing surgical approaches for OSDs were included. In conclusion, surgical options for OSDs offer significant benefits when non-invasive treatments fail. Surgical techniques such as punctal occlusion, eyelid fissure narrowing, AMT, and conjunctival flap procedures help stabilize the ocular surface and alleviate symptoms. Advanced methods like CN and SGT target the underlying pathology in refractory cases such as oGVHD. The outcomes vary depending on the disease severity and surgical approach. Each procedure carries specific risks and requires individualized patient selection. Therefore, a tailored approach based on clinical condition, anatomical involvement, and patient factors is essential to achieve optimal results. Ongoing innovations in reconstructive surgery and regenerative medicine are expected to further improve outcomes for patients with OSDs. Full article

Background/Objectives: Pregnancies complicated by idiopathic polyhydramnios are linked to a heightened risk of numerous maternal and perinatal complications. We aim to study the implications of polyhydramnios in term pregnancies complicated with gestational diabetes mellitus (GDM). Methods: A prospective cohort study including 340 GDM cases was conducted. An ultrasound scan was conducted at term between 37 and 40 weeks and amniotic fluid volume (AFV) was assessed by measuring the amniotic fluid index (AFI) and the single deepest pocket (SDP). Maternal demographics and obstetric and perinatal outcomes were evaluated after delivery. We performed comparisons between groups with normal AFV and polyhydramnios (AFI ≥ 24 cm or SDP ≥ 8 cm), and between groups with normal and increased AFV (AFI or SDP ≥ 75th centile). A multivariate logistic regression analysis was performed to study association between AVF measurements and adverse maternal and perinatal outcomes. Results: We found that women with GDM and polyhydramnios at term had a higher risk of maternal (54.3 vs. 27.5%, p < 0.001) and perinatal adverse outcomes (65.7% vs. 46.5%, p < 0.03). The increased AFV group showed a higher risk of fetal overgrowth (LGA: 21.4% vs. 8.2%, p < 0.001 and macrosomia: 19.8% vs. 5.4%, p < 0.001, respectively) and a lesser risk of delivering an SGA fetus (6.3% vs. 13.6%, respectively). Both AFI and SDP showed a significant correlation with newborn weight (r = 0.27; p < 0.001 and r = 0.28; p < 0.001, respectively) and newborn centile (r = 0.26; p < 0.001 and r = 0.26 for both). Subsequent to conducting a multivariate logistic regression analysis adjusted for pregestational BMI, nulliparity, and insulin treatment, both AFI and SDP were significantly associated with perinatal complications, but AFI showed a stronger association with fetal overgrowth (aOR 1.11; p = 0.004 for a LGA fetus and aOR 1.12; p = 0.002 for macrosomia) and with lower risk of delivering an SGA fetus (aOR 0.89; p = 0.009) or IUGR fetus (aOR 0.86; p = 0.03). ROC analysis showed a poor diagnostic performance of both AFI and SDP for identifying macrosomia (AUC 0.68 for AFI, and 0.65 for SDP). Conclusions: Detection of polyhydramnios at term, whether using AFI or SDP, identifies a subgroup of women with gestational diabetes with higher risks of obstetric and perinatal complications. Cases with increased AFV (AFI ≥ 18 cm or SDP ≥ 6.5 cm) are also associated with an increased risk of fetal overgrowth and may require more intensive monitoring for management and optimal delivery timing, with the aim of improve perinatal outcomes. Full article

Body stalk anomaly (BSA) is a rare and usually fatal congenital disorder involving severe malformations of the body wall, limbs, spine, and internal organs. This study presents the first documented cases of BSA in seven dogs, offering new insights into how the disorder manifests in animals. The affected fetuses consistently exhibited major anomalies, including large abdominal wall defects, structural spinal abnormalities, and a variety of limb malformations ranging from partial agenesis and meromelia to phocomelia and complete amelia. Structural urogenital anomalies and orofacial clefts were also observed, aligning with similar findings in BSA cases reported in pigs and cats. These findings support the hypothesis of a multifactorial etiology involving early embryonic disruptions, such as abnormal folding of the embryo, rupture of the amniotic membrane, and vascular compromise. The frequent occurrence of abdominal wall defects alongside umbilical cord abnormalities further suggests a shared developmental pathway. This study also highlights the value of veterinary cases in comparative embryology and the need to assess congenital anomalies as part of a broader malformation complex. By expanding the phenotypic spectrum of BSA in domestic animals, this work contributes to a deeper understanding of its pathogenesis and emphasizes the importance of further research into the genetic and environmental factors involved. Such efforts could lead to improved classification and diagnosis of complex congenital malformations, as well as facilitate cross-species comparisons. Full article

Research in the field of stem cells in necrotizing enterocolitis has primarily focused on the curative role of specific cells—mostly bone marrow and amniotic fluid stem cells. The impact of stem cells on reducing inflammatory cytokine levels in the necrotizing enterocolitis (NEC) model has been studied in accordance with the effects they pose on histopathology. Taking into consideration the possible paracrine mechanism of action of stem cells, our group hypothesized that lowering the initial levels of proinflammatory cytokines may be one of the mechanisms affecting the clinical outcome. A self-modified rat NEC model was used to show the effect of intraperitoneal administration of adipose derived stem cells on the initial levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alfa) in comparison with the interleukin levels in NEC animals and control animals without adipose–derived stem cells (ADSCs) injection. We showed a statistically significant difference in the levels of interleukins when comparing an ADSC injected group and an NEC group. This suggests that one of the mechanisms in which stem cells impact the clinical outcomes in NEC may be by alleviating the initial levels of proinflammatory cytokines. Full article

Wound healing involves complex interplay between cellular and molecular events. In this study, we investigated the therapeutic potential of the bovine amniotic membrane (BAM) in wound healing using a mouse model. Twelve male C57BL/6 mice were divided into four groups: negative control (Vehicle), positive control (DuoDERM Extra Thin^®), amniotic membrane attachment (Amniotic Membrane), and compressed amniotic membrane attachment (Amniotic Membrane with Compression). The dorsal skin of each mouse was excised and wound-healing parameters were assessed over a two-week period. Our results revealed that the Amniotic Membrane and Amniotic Membrane with Compression groups demonstrated significant sustained reductions in the wound area compared to the Vehicle group. These reductions were more pronounced than those observed in the DuoDERM group. Histopathological analysis revealed advanced wound healing characteristics in the BAM-treated groups. Immunohistochemical analysis demonstrated elevated expression levels of wound healing markers (including α-smooth muscle actin, collagen type III, SMAD 1/5/8, and SMAD 2/3) in the BAM-treated groups compared to the control and DuoDERM groups. Conversely, cluster of differentiation 4 levels were significantly lower in BAM-treated groups. Overall, our findings highlight the therapeutic efficacy of BAM and compression in promoting wound healing. Thus, BAM offers a promising therapeutic approach for enhancing wound healing outcomes in clinical settings, potentially by modulating key wound healing pathways and processes. Full article

Background: Numerous experimental studies aim to improve outcomes of peripheral nerve repair following trauma. This study evaluates the efficacy of the human epineural patch (hEP) compared to the human amniotic membrane (hAM) in promoting nerve regeneration following sciatic nerve crush injury. Methods: Thirty-six athymic nude rats were divided into three groups (n = 12 per group) following nerve crush: (1) an unprotected injury site; (2) crush injury wrapped with hEP; and (3) crush injury wrapped with hAM. Animals were assessed over 6 or 12 weeks post-injury. Evaluations included motor recovery (Toe-Spread test), sensory recovery (Pinprick test), muscle denervation atrophy (the gastrocnemius muscle index (GMI)), histomorphometry (myelin thickness, axonal density, fiber diameter, and percentage of myelinated fibers), and immunofluorescence (GFAP, Laminin B, NGF, S-100, VEGF, vWF, HLA-DR, and HLA-I) assessments. Results: The hEP group showed superior motor recovery, axonal density and higher GMI values compared to the hAM and control groups. The increased expression of neurogenic and angiogenic markers highlighted its neuroregenerative potential. Negligible HLA-DR and HLA-I expression confirmed the lack of hEP and hAM immunogenicity. Conclusions: The application of hEP following sciatic nerve crush injury facilitated nerve regeneration, improved functional outcomes, and offered a viable alternative to hAM. Structural stability and the regenerative capacity position hEP as a new, promising off-the-shelf product for nerve regeneration. Full article

Background/Objectives: Advanced wound healing biologics for diabetic foot ulcer (DFU) are typically withheld from persons who are at high risk for amputation. However, a prospective, single-center cohort study evaluated the use of an advanced biologic, dehydrated amniotic (DAMA) tissue as early treatment for DFUs in patients with a high risk for amputation, demonstrating benefit for a small sample. This is the report of the five-year follow-up of those high-risk participants. Methods: This chart review provides a 5-year follow-up of 18 of 20 participants in the original study. The data were collected by medical record review. Specific data points included mortality, re-ulceration and additional ulceration, amputation (minor and major), end-stage renal disease with dialysis dependence, hospitalization, and limb-threatening ischemia. Results: The 5-year mortality rate from the time of wound healing was 50% (9/18 deceased). Four of the eighteen participants (22.2%) underwent major amputation within 5 years of study completion. Two had amputations of the study limb and two had amputations of the contralateral limb. Fifty percent (2/4) of those who had amputations died within 5 years after the major amputation. Over fifty percent (55.5% or 10 out of 18) of the participants experienced the re-ulceration of the original study ulcer and 94% (17 out of 18) developed a new site ulceration. A total of 25% of the hospitalizations over the 5 years were related to DFU (infection, osteomyelitis, and sepsis). Conclusions: This small-sample 5-year follow-up shows that early treatment with dehydrated amniotic (DAMA) tissue in patients with diabetic foot ulcers of moderate-to-high amputation risk results in similar outcomes as noted in the current research on patients with low risk for amputation. In fact, this paper may suggest that advanced biologics can safely be used for early treatment in moderate-to-high amputation risk without increasing mortality and amputation over 5 years. Full article

Background and Clinical Significance: Prader–Willi syndrome (PWS) is a rare genetic disease caused by imprinted gene dysfunction, typically involving deletion of the chromosome 15q11.2-q13 region, balanced translocation, or related gene mutations in this region. PWS presents with complex and varied clinical manifestations. Abnormalities can be observed from the fetal stage and change with age, resulting in growth, developmental, and metabolic issues throughout different life stages. Case Presentation: We report the prenatal characteristics observed from the second to third trimester of pregnancy in a neonate with PWS. Prenatal ultrasound findings included a single umbilical artery, poor abdominal circumference growth from 26 weeks, normal head circumference and femur length growth, increased amniotic fluid volume after 30 weeks, undescended fetal testicles in the third trimester, small kidneys, and reduced fetal movement. The male infant was born at 38 weeks of gestation with a birth weight of 2580 g. He had a weak cry; severe hypotonia; small eyelid clefts; bilateral cryptorchidism; low responsiveness to medical procedures such as blood drawing; and poor sucking, necessitating tube feeding. Blood methylation-specific multiple ligation-dependent probe amplification (MS-MLPA) showed paternal deletion PWS. Notably, this case revealed two previously unreported prenatal features in PWS: a single umbilical artery and small kidneys. Conclusions: Through literature review and our case presentation, we suggest that a combination of specific sonographic features, including these newly identified markers, may aid clinicians in the early diagnosis of PWS. Full article

Background: Charcot–Marie–Tooth disease (CMT) is a genetically and clinically heterogeneous group of progressive peripheral neuropathies. Preimplantation genetic testing for monogenic disorders (PGT-M), a well-established assisted reproductive technology used to detect specific genetic mutations in embryos before implantation, has been used in common CMT subtypes (e.g., CMT1A); however, data on its application across rarer subtypes and in de novo cases remain limited. In this study, we aimed to evaluate the effectiveness of PGT-M using karyomapping in achieving clinical pregnancies and healthy births in families affected by various CMT types, including the previously unreported subtypes CMT1B and CMT2. Methods: We analyzed 31 PGT-M cycles from 13 families with genetically confirmed CMT, including cases of previously unreported subtypes CMT1B and CMT2. A total of 150 embryos were biopsied. Through 19 embryo transfer cycles, 21 embryos were transferred. In one de novo case, karyomapping was performed using amniotic fluid from an affected fetus as a reference. Results: Of the 19 embryo transfers, 15 resulted in clinical pregnancies. Prenatal diagnosis confirmed that all fetuses were unaffected, and all pregnancies resulted in healthy live births. Successful phasing using amniotic fluid from an affected fetus enabled accurate embryo selection and led to the birth of healthy twins. Conclusions: PGT-M using karyomapping is a rapid and reliable method for achieving successful pregnancies in families affected by diverse CMT subtypes, including de novo cases, and supports broader applicability to other monogenic disorders. Full article

Caspases are a family of cysteine-dependent aspartate-directed proteases implicated in programmed cell death. Humans have eleven proteolytically active caspases, namely caspase-1 through -10 and caspase-14. The latter is expressed exclusively in epithelial cells and constitutively resides in its active form in the cornified layer of the human epidermis. Molecular phylogenetics has revealed that caspase-14 belongs to a subfamily of caspases, which also includes caspase-15 and -16. The latter are evolutionarily more ancient than caspase-14 and have been lost in the phylogenetic lineage leading to humans. Here, we review the molecular properties, the species distributions, and the biological roles of caspase-14-like proteases in amniotes. In contrast to the prodomain-less caspase-14, caspase-15 contains a prodomain that is predicted to assume a pyrin fold, and caspase-16 features a prodomain with unique sequence similarity to the catalytic domain. Gene knockout in mice, evolutionary gene loss in aquatic mammals and the association of human CASP14 mutations with ichthyosis indicate that caspase-14 is associated with the barrier function of mammalian skin. Caspase-15 is able to induce apoptosis in cell culture, but its role in vivo and the role of caspase-16 are currently unknown. We propose directions for research to further characterize caspase-14-like proteases. Full article

Preterm delivery affects approximately 10% of pregnancies worldwide and remains a major clinical challenge due to the lack of reliable early predictive tools. Existing strategies are often invasive, relying on blood or amniotic fluid samples and requiring complex processing. In this study, we describe a novel non-invasive approach based on the multiplex detection of inflammatory cytokines in small urine volumes from pregnant women. To account for clinical and temporal variability, we applied Generalized Additive Models for Location, Scale, and Shape (GAMLSS) to adjust for gestational age at sampling and obstetric factors. Correlation network analyses revealed cytokine interactions that distinguished preterm from term deliveries, with macrophage-derived cytokines—MIP-1α, MIP-1β, IL-15, and IL-22—emerging as central nodes. These findings highlight the involvement of the IL-1 pathway in the pathophysiology of preterm labor. Furthermore, urinary IL-5 and IL-31 levels correlated positively with pregnancy duration, whereas IL-1β and IL-1Ra in urine and TNFα in amniotic fluid showed inverse associations. Altogether, this non-invasive methodology provides insight into immune dynamics during pregnancy and offers a foundation for future studies focused on biomarker discovery and mechanistic understanding of preterm birth. Full article