Modified Z-plasty of the Patellar Ligament with Reinforcement of the Quadriceps Tendon in the Treatment of Patella Baja.

Patella baja is an infrequent knee pathology, but it is limiting due to joint stiffness and localized pain in the anterior region of the knee. It may occur after trauma, prolonged immobilization or local surgical intervention. The striking pathological finding is the shortening and increase in thickness of the patellar ligament. Several surgical techniques have been described for its treatment, and there is no standardized treatment. We describe the case of a 73-year-old female patient who presented with knee stiffness, significant functional deficit, and patella baja after total knee arthroplasty. She underwent a recently described soft tissue surgical procedure, with excellent functional evolution, improving from a Lysholm Knee Score of 16 to 81 points, allowing early mobilization and return to daily life activities.

Endobronchial Ulceration: A Different Manifestation of Antineutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis.

Vasculitis with pulmonary involvement is often associated with antineutrophil cytoplasmic antibody (ANCA). We describe a case involving a 66-year-old male patient diagnosed with granulomatosis with polyangiitis (GPA). Following the onset of hemoptysis, bronchoscopy revealed endobronchial ulcers correlated with GPA. Bronchial biopsies and bronchoalveolar lavage identified Staphylococcus aureus (S. aureus), which is associated with GPA relapses. The patient began immunosuppression to induce remission, and Avacopan was subsequently introduced for the treatment of GPA and microscopic polyangiitis (MPA).

Carbon savings from sugarcane straw-derived bioenergy: Insights from a life cycle perspective including soil carbon changes.

Sugarcane straw removal for bioenergy production will increase substantially in the next years, but this may deplete soil organic carbon (SOC) and exacerbate greenhouse gas (GHG) emissions. These aspects are not consistently approached in bioenergy life cycle assessment (LCA). Using SOC modeling and LCA approach, this study addressed the life cycle GHG balance from sugarcane agroindustry in different scenarios of straw removal, considering the potential SOC changes associated with straw management in sugarcane-cultivated soils in Brazil. Long-term simulations showed SOC losses of up to -0.5 Mg ha-1 yr-1 upon complete straw removal, whereas the moderate removal had little effects on SOC and the maintenance of all straw in the field increased SOC accumulation by up to 0.4 Mg ha-1 yr-1. Our analysis suggests that accounting for SOC changes in LCA calculations could lower the net GHG benefits of straw-derived bioenergy, whose emissions intensity varied according to soil type. Overall, SOC depletion induced by complete straw removal increased the life cycle GHG emissions of straw-derived bioenergy by 26 % (3.9 g CO2eq MJ-1) compared to a scenario without taking SOC changes into account. Straw removal for cellulosic ethanol could be effective for mitigating GHG emissions relative to gasoline, but it was not advantageous for bioelectricity generation depending on the energy sources that are displaced. Therefore, straw-induced change of SOC stocks is a critical factor to model life cycle GHG emissions of straw-derived bioenergy.

Preparation and Characterization of Zinc Ferrite and Gadolinium Iron Garnet Composite for Biomagnetic Applications.

Cancer is a major worldwide public health problem. Although there have already been astonishing advances in cancer diagnosis and treatment, the scientific community continues to make huge efforts to develop new methods to treat cancer. The main objective of this work is to prepare, using a green sol-gel method with coconut water powder (CWP), a new nanocomposite with a mixture of Gd3Fe5O12 and ZnFe2O4, which has never been synthesized previously. Therefore, we carried out a structural (DTA-TG and X-ray diffraction), morphological (SEM), and magnetic (VSM and hyperthermia) characterization of the prepared samples. The prepared nanocomposite denoted a saturation magnetization of 11.56 emu/g at room temperature with a ferromagnetic behavior and with a specific absorption rate (SAR) value of 0.5 ± 0.2 (W/g). Regarding cytotoxicity, for concentrations < 10 mg/mL, it does not appear to be toxic. Although the obtained results were interesting, the high particle size was identified as a problem for the use of this nanocomposite.

Diagnostic Test Accuracy of Urinary DNA Methylation-based Biomarkers for the Detection of Primary and Recurrent Bladder Cancer: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: Diagnosis of primary and relapsed bladder carcinomas is accomplished by urethrocystoscopy, an invasive procedure, combined with urinary cytology, with limited sensitivity, resulting in a substantial burden. Thus, noninvasive biomarkers have been investigated, among which DNA methylation has shown promise. This systematic review and meta-analysis sought to assess the diagnostic accuracy of DNA methylation biomarkers reported in the literature for bladder cancer detection, pinpointing the most informative one. METHODS: The search for this systematic review and meta-analysis was conducted on PubMed, Scopus, and Cochrane Library for relevant studies published until December 31, 2022. A meta-analysis was performed using a random-effect model, to compute the pooled sensitivity and specificity of the markers. PROSPERO's registration ID for the study is CRD42023397703. KEY FINDINGS AND LIMITATIONS: Out of the 2297 studies retrieved, 68 were included in the final analysis, despite considerable heterogeneity. These involved 12 696 participants, of whom 5557 were diagnosed with bladder cancer. Using diagnostic odds ratio (DOR) as a comparative measure, the five most promising markers (pooled sensitivity, specificity, and DOR) were SALL3 (61%, 97%, and 55.67, respectively), PENK (77%, 93%, and 47.90, respectively), ZNF154 (87%, 90%, and 45.07, respectively), VIM (82%, 90%, and 44.81, respectively), and POU4F2 (81%, 89%, and 34.89, respectively). Urinary cytology identified bladder cancer with 55% sensitivity, 92% specificity, and 14.37 DOR. CONCLUSIONS AND CLINICAL IMPLICATIONS: DNA methylation biomarkers disclose high accuracy for bladder cancer detection in urine. Nonetheless, validation studies in different clinical settings are scarce, hampering clinical use. The identified biomarkers should be prioritized in future validation studies. PATIENT SUMMARY: In this meta-analysis, we include previously published studies that used urine samples of bladder cancer patients' from all around the globe. We were able to compare the diagnostic accuracy of noninvasive markers across different populations. We were able to conclude on the most promising DNA methylation markers to detect bladder cancer using urine.

Unraveling the evolutionary origin of the complex Nuclear Receptor Element (cNRE), a cis-regulatory module required for preferential expression in the atrial chamber.

Cardiac function requires appropriate proteins in each chamber. Atria requires slow myosin to act as reservoirs, while ventricles demand fast myosin for swift pumping. Myosins are thus under chamber-biased cis-regulation, with myosin gene expression imbalances leading to congenital heart dysfunction. To identify regulatory inputs leading to cardiac chamber-biased expression, we computationally and molecularly dissected the quail Slow Myosin Heavy Chain III (SMyHC III) promoter that drives preferential expression to the atria. We show that SMyHC III gene states are orchestrated by a complex Nuclear Receptor Element (cNRE) of 32 base pairs. Using transgenesis in zebrafish and mice, we demonstrate that preferential atrial expression is achieved by a combinatorial regulatory input composed of atrial activation motifs and ventricular repression motifs. Using comparative genomics, we show that the cNRE might have emerged from an endogenous viral element through infection of an ancestral host germline, revealing an evolutionary pathway to cardiac chamber-specific expression.

Humoral Immune Response to SARS-CoV-2 Spike Protein Receptor-Binding Motif Linear Epitopes.

The worldwide spread of SARS-CoV-2 has led to a significant economic and social burden on a global scale. Even though the pandemic has concluded, apprehension remains regarding the emergence of highly transmissible variants capable of evading immunity induced by either vaccination or prior infection. The success of viral penetration is due to the specific amino acid residues of the receptor-binding motif (RBM) involved in viral attachment. This region interacts with the cellular receptor ACE2, triggering a neutralizing antibody (nAb) response. In this study, we evaluated serum immunogenicity from individuals who received either a single dose or a combination of different vaccines against the original SARS-CoV-2 strain and a mutated linear RBM. Despite a modest antibody response to wild-type SARS-CoV-2 RBM, the Omicron variants exhibit four mutations in the RBM (S477N, T478K, E484A, and F486V) that result in even lower antibody titers. The primary immune responses observed were directed toward IgA and IgG. While nAbs typically target the RBD, our investigation has unveiled reduced seroreactivity within the RBD's crucial subregion, the RBM. This deficiency may have implications for the generation of protective nAbs. An evaluation of S1WT and S2WT RBM peptides binding to nAbs using microscale thermophoresis revealed a higher affinity (35 nM) for the S2WT sequence (GSTPCNGVEGFNCYF), which includes the FNCY patch. Our findings suggest that the linear RBM of SARS-CoV-2 is not an immunodominant region in vaccinated individuals. Comprehending the intricate dynamics of the humoral response, its interplay with viral evolution, and host genetics is crucial for formulating effective vaccination strategies, targeting not only SARS-CoV-2 but also anticipating potential future coronaviruses.

Arthrogryposis Multiplex Congenita and the Importance of Orthoses: A Case Report.

Arthrogryposis multiplex congenita (AMC) is a group of conditions characterized by multiple joint contractures. This rare disorder causes stiffness of joints, limiting the range of motion and negatively impacting activities of daily living (ADL). This case reports a 45-year-old male with AMC who was referred to physical medicine and rehabilitation (PMR). He had a limited range of movement in multiple joints and global muscle weakness. However, ADL were feasible, including walking. The patient had an unsteady barefoot gait, causing claudication, which improved significantly with adapted shoes. The primary goal of treatment is to improve the quality of life (QoL), and proper management should be promptly initiated. AMC requires a multidisciplinary approach to care with three mainstays of treatment: rehabilitation, orthoses, and corrective surgeries. Patients should be followed up periodically by their family doctors, and PMR evaluations and rehabilitation should be provided as needed. An orthopedic surgery consultation may be required for surgical interventions to provide optimal outcomes and augment the QoL.

Mammal responses to global changes in human activity vary by trophic group and landscape.

Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human-wildlife interactions along gradients of human influence.

Fever as a Predictor of COVID-19 Outcomes in Hospitalized Patients.

INTRODUCTION: With the advent of the COVID-19 pandemic, numerous questions have arisen regarding the screening, diagnosis, treatment, and prognosis of infected patients. Among these, screening infected patients through body temperature measurement has proven ineffective. However, doubts persist regarding the role of fever as a prognostic factor in the disease. OBJECTIVE: To assess the prevalence of fever and its relevance as a marker of mortality in COVID-19. METHODOLOGY: This prospective and longitudinal cohort study was conducted between April 2020 and December 2021 and analyzed 1400 COVID-19 patients systematically admitted to the emergency department of a reference hospital during the period from April 2020 to December 2021, in the city of Curitiba, Brazil. [LG1] The study evaluated [LG2] the presence of fever (body temperature above 37,7ºC) upon admission and/or during hospitalization, patient profiles, and outcomes (in-hospital death, discharge, admission at the intensive care unit, need of mechanical ventilation). RESULTS: Fever was present in 128 participants (9.1%), with a higher prevalence in males (71%) and obese individuals (42.9%). Among the febrile patients, 39 required intubation (30.4%), with two intubated upon admission (1.5%), 104 were discharged (81.2%), and 24 deceased (18.7%). Fever was not associated with a higher mortality rate. CONCLUSION: Fever showed low prevalence, is more common in males and obese individuals, and is not related to worse clinical outcomes.

E-cadherin variants associated with oral facial clefts trigger aberrant cell motility in a REG1A-dependent manner.

BACKGROUND: Germline mutations of E-cadherin contribute to hereditary diffuse gastric cancer (HDGC) and congenital malformations, such as oral facial clefts (OFC). However, the molecular mechanisms through which E-cadherin loss-of-function triggers distinct clinical outcomes remain unknown. We postulate that E-cadherin-mediated disorders result from abnormal interactions with the extracellular matrix and consequent aberrant intracellular signalling, affecting the coordination of cell migration. METHODS: Herein, we developed in vivo and in vitro models of E-cadherin mutants associated with either OFC or HDGC. Using a Drosophila approach, we addressed the impact of the different variants in cell morphology and migration ability. By combining gap closure migration assays and time-lapse microscopy, we further investigated the migration pattern of cells expressing OFC or HDGC variants. The adhesion profile of the variants was evaluated using high-throughput ECM arrays, whereas RNA sequencing technology was explored for identification of genes involved in aberrant cell motility. RESULTS: We have demonstrated that cells expressing OFC variants exhibit an excessive motility performance and irregular leading edges, which prevent the coordinated movement of the epithelial monolayer. Importantly, we found that OFC variants promote cell adhesion to a wider variety of extracellular matrices than HDGC variants, suggesting higher plasticity in response to different microenvironments. We unveiled a distinct transcriptomic profile in the OFC setting and pinpointed REG1A as a putative regulator of this outcome. Consistent with this, specific RNAi-mediated inhibition of REG1A shifted the migration pattern of OFC expressing cells, leading to slower wound closure with coordinated leading edges. CONCLUSIONS: We provide evidence that E-cadherin variants associated with OFC activate aberrant signalling pathways that support dynamic rearrangements of cells towards improved adaptability to the microenvironment. This proficiency results in abnormal tissue shaping and movement, possibly underlying the development of orofacial malformations.

Molecular detection and characterization of Blastocystis in herbivore livestock species in Portugal.

Blastocystis is a ubiquitous intestinal protist in humans and animals worldwide. The traditional livestock free-roaming raising system in rural communities increases the risk of infection with contact with a wider range of pathogens transmitted via the faecal-oral route associated with that wildlife-livestock-human interface. However, no studies have been conducted to determine the occurrence and subtype distribution of Blastocystis in livestock in Portugal. Here, we collected 180 faecal samples from herbivore livestock (cattle, goats, horses, and sheep) in different regions of the country to investigate Blastocystis prevalence and subtype diversity using PCR and next-generation amplicon sequencing. Blastocystis was present in 40.6% (73/180; 95% CI: 33.31-48.11) of the samples (goats, 81.0%; sheep, 60.9%; cattle, 32.2%). None of the horse samples were Blastocystis-positive. Eighteen subtypes were detected (ST1-ST3, ST5-ST7, ST10, ST13, ST14, ST21, ST23-ST26, ST30, ST42-ST44). Mixed infections were detected in 97.3% of the Blastocystis-positive samples. Potentially zoonotic subtypes were identified in 75.0%, 96.4%, and 100% of the Blastocystis-positive specimens collected from cattle, sheep, and goats, respectively. These results demonstrate that cattle, sheep, and goats harbour a high diversity of Blastocystis subtypes in the study regions. Importantly, our data provide novel molecular evidence strongly suggesting that some Blastocystis STs/ST subgroups may have differential host specificity.

Dynamical model of antibiotic responses linking expression of resistance genes to metabolism explains emergence of heterogeneity during drug exposures.

Antibiotic responses in bacteria are highly dynamic and heterogeneous, with sudden exposure of bacterial colonies to high drug doses resulting in the coexistence of recovered and arrested cells. The dynamics of the response is determined by regulatory circuits controlling the expression of resistance genes, which are in turn modulated by the drug's action on cell growth and metabolism. Despite advances in understanding gene regulation at the molecular level, we still lack a framework to describe how feedback mechanisms resulting from the interdependence between expression of resistance and cell metabolism can amplify naturally occurring noise and create heterogeneity at the population level. To understand how this interplay affects cell survival upon exposure, we constructed a mathematical model of the dynamics of antibiotic responses that links metabolism and regulation of gene expression, based on the tetracycline resistancetetoperon inE. coli. We use this model to interpret measurements of growth and expression of resistance in microfluidic experiments, both in single cells and in biofilms. We also implemented a stochastic model of the drug response, to show that exposure to high drug levels results in large variations of recovery times and heterogeneity at the population level. We show that stochasticity is important to determine how nutrient quality affects cell survival during exposure to high drug concentrations. A quantitative description of how microbes respond to antibiotics in dynamical environments is crucial to understand population-level behaviors such as biofilms and pathogenesis.

Probing molecules in gas cells of subwavelength thickness with high frequency resolution.

Miniaturizing and integrating atomic vapor cells is widely investigated for the purposes of fundamental measurements and technological applications such as quantum sensing. Extending such platforms to the realm of molecular physics is a fascinating prospect that paves the way for compact frequency metrology as well as for exploring light-matter interactions with complex quantum objects. Here, we perform molecular rovibrational spectroscopy in a thin-cell of micrometric thickness, comparable to excitation wavelengths. We operate the cell in two distinct regions of the electromagnetic spectrum, probing ν1 + ν3 resonances of acetylene at 1.530 µm, within the telecommunications wavelength range, as well as the ν3 and ν2 resonances of SF6 and NH3 respectively, in the mid-infrared fingerprint region around 10.55 µm. Thin-cell confinement allows linear sub-Doppler transmission spectroscopy due to the coherent Dicke narrowing effect, here demonstrated for molecular rovibrations. Our experiment can find applications extending to the fields of compact molecular frequency references, atmospheric physics or fundamental precision measurements.

Spatiotemporal Modulation for Ultrasonic Mid-Air Haptics: Sensation's Specification and Validation.

Spatiotemporal modulation (STM) is used in Ultrasonic Mid-Air Haptics to create compelling tactile sensations. The STM can create perceptually distinct sensations. We specified the sensations of a palm-size pattern by varying the focal point's speed and pattern sampling rate. Three sensations were specified, named as Dynamic, Vibratory and Uniform. A selective identification study was conducted to evaluate if the sensations were recognizable to the perception when presented individually and simultaneously (combined stimuli). The results support the STM's specification and the selective recognition of the sensations was possible for some combinations.

Central and mixed apneas in children with obstructive sleep apnea: effect of adenotonsillectomy.

PURPOSE: Investigate the effect of adenotonsillectomy on mixed apnea index (MAI) and central apnea index (CAI) in children with moderate-to-severe obstructive sleep apnea syndrome (OSAS). METHODS: Observational retrospective analysis of polysomnographic data in children diagnosed with moderate-to-severe OSAS and without comorbidity, submitted to adenotonsillectomy. RESULTS: Data were available for 80 children, 55 boys and 25 girls, with a median age of 3.6 years (2.1-5.9). Before surgery AHI was 14.1 (11.0-18.4) per hour, with a median preoperative OAI of 7.1 (4.1-10.6), MAI of 1.2 (0.6-1.6) and CAI of 1.0 (0.4-2.0). Adenotonsillectomy caused significant improvements in MAI, from 1.2 (0.6-1.6) to 0.5 (0.1-0.8) (p < 0.001) and CAI from 1.0 (0.4-2.0) to 0.5 (0.1-0.9) (p < 0.001). This represents a normalization of MAI in 91.7% and CAI in 75.6% of children that had an abnormal value prior surgery. CONCLUSION: Non obstructive apneas are common in children with OSAS. Adenotonsillectomy caused significant decrease not only in OAI, but also in MAI and CAI in children with moderate-to-severe OSAS.

Early-Onset Dystonia and Visual Impairment Preceding Epileptic Encephalopathy Associated with PIGA Gene Mutation.

The association between dystonia and early-onset epileptic encephalopathy (EOEE) may have a genetic basis. Phosphatidylinositol glycan biosynthesis class A protein (PIGA) germline mutations have been described in the last decade and associated with refractory EOEEs. Dysmorphisms and visceral abnormalities have also been reported. Here, we present the case of a now 8-month-old child who was evaluated for dystonia, visual impairment, and developmental delay at 2 months of age, followed by refractory focal seizures when he was 4 months old. The remaining examination was normal, besides an accelerated linear growth. His brain magnetic resonance and an extensive metabolic investigation failed to show any abnormalities. At 7 months of age, the exome sequencing found a hemizygous PIGA pathogenic variant-c.1352T > C (p.(Ile451Thr). Seizures improved after the association of carbamazepine with levetiracetam and the beginning of the ketogenic diet. To our knowledge, this is the first time the phenotype associated with this specific mutation is described. Our patient had the singularity of manifesting with remarkable dystonia, over 2 months before the onset of seizures. We also point to the utility of the gene sequencing approach in the diagnosis of patients with dystonia and EOEEs, since identification of the genetic cause may help in patient's management and families' empowerment.

The Mediterranean mussel Mytilus galloprovincialis: a novel model for developmental studies in mollusks.

A model organism in developmental biology is defined by its experimental amenability and by resources created for the model system by the scientific community. For the most powerful invertebrate models, the combination of both has already yielded a thorough understanding of developmental processes. However, the number of developmental model systems is still limited, and their phylogenetic distribution heavily biased. Members of one of the largest animal lineages, the Spiralia, for example, have long been neglected. In order to remedy this shortcoming, we have produced a detailed developmental transcriptome for the bivalve mollusk Mytilus galloprovincialis, and have expanded the list of experimental protocols available for this species. Our high-quality transcriptome allowed us to identify transcriptomic signatures of developmental progression and to perform a first comparison with another bivalve mollusk: the Pacific oyster Crassostrea gigas. To allow co-labelling studies, we optimized and combined protocols for immunohistochemistry and hybridization chain reaction to create high-resolution co-expression maps of developmental genes. The resources and protocols described here represent an enormous boost for the establishment of Mytilus galloprovincialis as an alternative model system in developmental biology.