Site-Selective Distal C(sp3)-H Bromination of Aliphatic Amines as a Gateway for Forging Nitrogen-Containing sp3 Architectures.

Herein, we disclose a new strategy that rapidly and reliably incorporates bromine atoms at distal, secondary C(sp3)-H sites in aliphatic amines with excellent and predictable site-selectivity pattern. The resulting halogenated building blocks serve as versatile linchpins to enable a series of carbon-carbon and carbon-heteroatom bond-formations at remote C(sp3) sites, thus offering a new modular and unified platform that expedites the access to advanced sp3 architectures possessing valuable nitrogen-containing saturated heterocycles of interest in medicinal chemistry settings.

Barbed versus conventional suture in elective posterior spine surgery.

PURPOSE: Barbed sutures are tissue control devices that can reduce operating room time and costs. We analyzed the utility of barbed sutures in posterior spinal surgery in order to prove non-inferiority to conventional methods for wound closure. METHODS: A cohort of patients undergoing elective posterior spinal surgery in which barbed (prospective) versus conventional sutures (retrospective) were used was analyzed. The primary endpoint was the occurrence of wound healing complications or the need for surgical revision. Secondary endpoints included postoperative stay, readmission rate, and duration and cost of wound closure. RESULT: A total of 483 patients participated in the study, 183 in the Barbed group and 300 in the Conventional group. Wound dehiscence or seroma occurred in 3.8% and 2.7% of the Barbed and Conventional groups, respectively (p = 0.6588). Both superficial (1.6% versus 4.0%, P = 0.2378) and deep infections (2.7% versus 4.7%, p = 0.4124) occurred similarly in both groups. Overall, the rate of re-intervention due to wound healing problems was also similar (4.9% versus 5.3%, p = 0.9906), as well as, total median hospital stay, postoperative stay and 30-day re-admission rates. The average duration of wound closure (1.66 versus 4.16 min per level operated, p < 0.0001) strongly favored the Barbed group. The mean cost of wound closure per patient was higher in the Barbed group (43.23 € versus 22.67 €, p < 0.0001). CONCLUSIONS: In elective posterior spinal procedures, the use of barbed sutures significantly reduced the duration of wound closure. The wound healing process was not hindered and the added cost related to the suture material was small.

Thyroid abscess, an uncommon diagnosis: A case report and mini­review of the literature.

Thyroid abscess is a rare entity, commonly experienced by immunocompromised patients, or those who have anatomical abnormalities or a pre-existing thyroid disease. An early diagnosis continued by treatment with antibiotics and drainage of the abscess is the recommended therapeutic strategy for such cases. The present study describes a clinical case of this rare event, and also provides a brief literature review. The present study describes the case of a 48-year-old healthy male with no medical antecedents, apart from acute prostatitis treated with antibiotics for 6 days prior, who visited the Emergency Department of the authors' hospital with neck pain and progressive swelling of the mass. Diagnostic imaging confirmed the authors' suspicion of an abscess and revealed the lesion displacing the airway to the contralateral side. This restricted the mobility of the neck of the patient. As an emergency measure, the patient was then taken to the operating room for a neck examination. A hemithyroidectomy was finally performed. Following a prolonged hospital duration, he was discharged from the hospital and his recovery was uneventful without any voice alterations, hypocalcemia or recurrence.

Perioperative risk factors for major complications after bone replacement in decompressive craniectomy.

INTRODUCTION: Bone flap replacement after a decompressive craniectomy is a low complexity procedure, but with complications that can negatively impact the patient's outcome. A better knowledge of the risk factors for these complications could reduce their incidence. PATIENTS AND METHODS: A retrospective review of a series of 50 patients who underwent bone replacement after decompressive craniectomy at a tertiary center over a 10-year period was performed. Those clinical variables related to complications after replacement were recorded and their risk factors were analyzed. RESULTS: A total of 18 patients (36%) presented complications after bone flap replacement, of which 10 (55.5%) required a new surgery for their treatment. Most of the replacements (95%) were performed in the first 90 days after the craniectomy, with a tendency to present more complications compared to the subsequent period (37.8% vs 20%, p > 0.05). The most frequent complication was subdural hygroma, which appeared later than infection, the second most frequent complication. The need for ventricular drainage or tracheostomy and the mean time on mechanical ventilation, ICU admission, or waiting until bone replacement were greater in patients who presented post-replacement complications. Previous infections outside the nervous system or the surgical wound was the only risk factor for post-bone flap replacement complications (p = 0.031). CONCLUSIONS: Postoperative complications were recorded in more than a third of the patients who underwent cranial bone flap replacement, and at least half of them required a new surgery. A specific protocol aimed at controlling previous infections could reduce the risk of complications and help establish the optimal time for cranial bone flap replacement.

Reciprocal communication between FAPs and muscle cells via distinct extracellular vesicle miRNAs in muscle regeneration.

Muscle regeneration is a complex process relying on precise teamwork between multiple cell types, including muscle stem cells (MuSCs) and fibroadipogenic progenitors (FAPs). FAPs are also the main source of intramuscular adipose tissue (IMAT). Muscles without FAPs exhibit decreased IMAT infiltration but also deficient muscle regeneration, indicating the importance of FAPs in the repair process. Here, we demonstrate the presence of bidirectional crosstalk between FAPs and MuSCs via their secretion of extracellular vesicles (EVs) containing distinct clusters of miRNAs that is crucial for normal muscle regeneration. Thus, after acute muscle injury, there is activation of FAPs leading to a transient rise in IMAT. These FAPs also release EVs enriched with a selected group of miRNAs, a number of which come from an imprinted region on chromosome 12. The most abundant of these is miR-127-3p, which targets the sphingosine-1-phosphate receptor S1pr3 and activates myogenesis. Indeed, intramuscular injection of EVs from immortalized FAPs speeds regeneration of injured muscle. In late stages of muscle repair, in a feedback loop, MuSCs and their derived myoblasts/myotubes secrete EVs enriched in miR-206-3p and miR-27a/b-3p. The miRNAs repress FAP adipogenesis, allowing full muscle regeneration. Together, the reciprocal communication between FAPs and muscle cells via miRNAs in their secreted EVs plays a critical role in limiting IMAT infiltration while stimulating muscle regeneration, hence providing an important mechanism for skeletal muscle repair and homeostasis.

Predicting histological grade in symptomatic meningioma by an objective estimation of the tumoral surface irregularity.

INTRODUCTION: Predicting the histopathologic grade of meningioma is relevant because local recurrence is significantly greater in WHO grade II-III compared to WHO grade I tumours, which would ideally benefit from a more aggressive surgical strategy. It has been suggested that higher WHO grade tumours are more irregularly-shaped. However, irregularity is a subjective and observer-dependent feature. In this study, the tumour surface irregularity of a large series of meningiomas, measured upon preoperative MRI, is quantified and correlated with the WHO grade. METHODS: Unicentric retrospective observational study of a cohort of symptomatic meningiomas surgically removed in the time period between January 2015 and December 2022. Using specific segmentation software, the Surface Factor (SF) was calculated for each meningioma. SF is an objective parameter that compares the surface of a sphere (minimum surface area for a given volume) with the same volume of the tumour against the actual surface of the tumour. This ratio varies from 0 to 1, being 1 the maximum sphericity. Since irregularly-shaped meningiomas present proportionally greater surface area, the SF tends to decrease as irregularity increases. SF was correlated with WHO grade and its predictive power was estimated with ROC curve analysis. RESULTS: A total of 176 patients (64.7% females) were included in the study; 120 WHO grade I (71.9%), 43 WHO grade II (25.7%) and 4 WHO grade III (2.4%). A statistically significant difference was found between the mean SF of WHO grade I and WHO grade II-III tumours (0.8651 ±â€¯0.049 versus 0.7081 ±â€¯0.105, p < 0.0001). Globally, the SF correctly classified more than 90% of cases (area under ROC curve 0.940) with 93.3% sensibility and 80.9% specificity. A cutoff value of 0.79 yielded the maximum precision, with positive and negative predictive powers of 82.6% and 92.6%, respectively. Multivariate analysis yielded SF as an independent prognostic factor of WHO grade. CONCLUSION: The Surface Factor is an objective and quantitative parameter that helps to identify aggressive meningiomas preoperatively. A cutoff value of 0.79 allowed differentiation between WHO grade I and WHO grade II-III with high precision.

Unwrapping the structural and functional features of antimicrobial peptides from wasp venoms.

The study of wasp venoms has captured attention due to the presence of a wide variety of active compounds, revealing a diverse array of biological effects. Among these compounds, certain antimicrobial peptides (AMPs) such as mastoparans and chemotactic peptides have emerged as significant players, characterized by their unique amphipathic short linear alpha-helical structure. These peptides exhibit not only antibiotic properties but also a range of other biological activities, which are related to their ability to interact with biological membranes to varying degrees. This review article aims to provide updated insights into the structure/function relationships of AMPs derived from wasp venoms, linking this knowledge to the potential development of innovative treatments against infections.

Single metachronous bone metastasis following rectal adenocarcinoma: A case report.

Colorectal cancer (CRC) ranks as the third leading cause of cancer-related mortality in developed countries. While its incidence in early stages has increased due to screening programs, a significant number of patients experience the development of metastases either at the time of diagnosis or during follow-ups. Unlike certain other types of cancer, such as breast, prostate, or lung cancer, where bone tissue is a common site for secondary dissemination, CRC primarily spreads to the lymph nodes, liver and lungs. The occurrence of bone metastases from CRC is rare and usually coincides with tumor involvement in other locations. Risk factors for bone metastases include the location of the primary tumor, the age of the patients, KRAS mutations and the degree of tumor differentiation. Unlike metastases to the liver and lungs, bone metastases tend to be symptomatic, affecting the patient's quality of life and resulting in a poorer prognosis with shorter survival rates. The approach to patient management needs to be personalized. The present study describes the of a patient who underwent surgery for stage IV rectal adenocarcinoma and later developed a metastasis in the costal wall 79 months post-intervention, with no evidence of recurrence at other sites.

Kinetically-Controlled Ni-Catalyzed Direct Carboxylation of Unactivated Secondary Alkyl Bromides without Chain Walking.

Herein, we report the direct carboxylation of unactivated secondary alkyl bromides enabled by the merger of photoredox and nickel catalysis, a previously inaccessible endeavor in the carboxylation arena. Site-selectivity is dictated by a kinetically controlled insertion of CO2 at the initial C(sp3)-Br site by the rapid formation of Ni(I)-alkyl species, thus avoiding undesired ß-hydride elimination and chain-walking processes. Preliminary mechanistic experiments reveal the subtleties of stereoelectronic effects for guiding the reactivity and site-selectivity.

Assessment of an intervention for preventing pediatric overweight and obesity through the World Café technique: A qualitative study.

PURPOSE: To evaluate the self-reported perspectives of participants involved in the Previene Cádiz intervention for preventing pediatric overweight and obesity. DESIGN AND METHODS: This qualitative study collected information through the World Café technique. A purposive sample of 40 participants was used, of which 14 were schoolchildren, 12 were teachers, and 14 were parent volunteers. The data were segmented, and concepts were created and grouped into dimensions and categories. RESULTS: The participants confirmed they had learned new information and behaviors about healthy habits. Parental awareness was considered a crucial and necessary element in changing family habits; therefore, increasing the motivation of family members was deemed a critical task in public health interventions conducted in school settings. DISCUSSION: Despite the suitability of qualitative methodology to evaluate the perceptions of the main players in an educational intervention, scientific literature is scarce. Obtaining information from the educational community about an intervention is not always easy, so the perspectives of teachers, students, and families about the Previene Cádiz intervention through the World Café approach is considered a relevant contribution. CONCLUSIONS: The participants considered the intervention positive in terms of learning and fostering increased knowledge, awareness, and healthy behaviors. PRACTICE IMPLICATIONS: Future interventions should encourage the active participation of all social groups involved, integrating dynamic and collaborative training activities that are acceptable to all participants.

Spontaneous cervical hematoma caused by giant parathyroid adenoma in an elderly patient: A case report.

Spontaneous cervical hematoma usually occurs as a consequence of extracapsular bleeding from a parathyroid gland, generally due to the presence of an adenoma (giant adenoma), glandular hyperplasia, cystic component, or, less frequently, due to the existence of a carcinoma. The hematoma can be confined to the cervical compartment or extend to the mediastinum, potentially causing airway compression. Despite this, the recommended management in hemodynamically stable patients consists of surveillance and hospital monitoring with delayed surgery after a few weeks. On the other hand, in those patients with airway compromise and instability, emergency surgery, consisting of cervicotomy and drainage, is mandatory. The present study describes the case of a 78-year-old patient with a medical history of high blood pressure, non-insulin-dependent diabetes mellitus, dyslipidemia, moderate aortic stenosis, chronic kidney disease and sarcoidosis under pharmacological treatment who attended the emergency department due to symptoms of neck pain, an increase in soft tissue, and dyspnea on moderate exertion with an evolution leading to respiratory failure. This was secondary to a diagnosis of spontaneous cervical hematoma that required urgent surgical intervention. The results of histopathological analysis revealed that a giant parathyroid adenoma was responsible for the bleeding. The patient had a complicated post-operative period with a prolonged admission to the intensive care unit.

Ring Walking Mediated by Ni-Ni Species as a Vehicle for Enabling Distal C(sp2)-H Functionalization of Aryl Pivalates.

Herein, we report the utilization of Ni-Ni species as a manifold for enabling a "ring-walking" event by dynamic translocation of the metal center over the arene backbone. Experimental and computational studies support a translocation occurring via a 1,2-hydride shift. The synthetic applicability of the method is illustrated in a series of C-C bond formations that occur at distal C(sp2)-H sites of simple aryl pivalates.

Ni-Catalyzed 1,2-Alkyl Borylation and Silylation of Allenes En Route to [1,3]-Bis-Organometallic Reagents.

A nickel-catalyzed multicomponent reaction that rapidly and reliably accesses [1,3]-bis-organometallic reagents from allenes is reported. The protocol exhibits a predictable regioselectivity pattern that enables the incorporation of B,B(Si) fragments across the allene backbone under mild conditions, thus offering a complementary platform for accessing polyorganometallic reagents possessing both sp2 and sp3 hybridization from readily available precursors.

Molecular diagnosis of cystic fibrosis by RNA obtained from nasal epithelial cells.

BACKGROUND: The diagnosis of cystic fibrosis (CF) is established when characteristic clinical signs are coupled with biallelic CFTR pathogenic variants. No previously reported non-canonical splice site variants have to be considered as variants of uncertain significance unless their effect on splicing has been validated. METHODS: Two variants identified by next-generation sequencing were evaluated. We assayed their effects on splicing employing RNA analysis and real-time expression quantification from RNA obtained from the nasal epithelial cells of a patient with clinically suspected CF and of two patients with milder phenotypes (CFTR-related disorders). RESULTS: The variant c.164+2dup causes skipping of exon 2 (p.(Ser18_Glu54del)) and exon 2 plus 3 (p.(Ser18Argfs*16)) in CFTR mRNA. Exon 2 expression in the patient heterozygous for c.164+2dup was decreased to 7 % of the exon 2 expression in the controls. The synonymous variant c.1584G>A causes a partial skipping of exon 11. The exon 11 expression in the two patients heterozygous for this variant was 22 % and 42 % of that of the controls, respectively. CONCLUSION: We conclude that variant c.164+2dup affects mRNA processing and can be considered a CF-causing variant. The results of the functional assay also showed that the p.(Glu528=) variant, usually categorized as a neutral variant based on epidemiological data, partially affects mRNA processing in our patients. This finding would allow us to reclassify the variant as a CFTR-related variant with incomplete penetrance. RNA obtained from nasal epithelial cells is an easy and accurate tool for CFTR functional studies in patients with unclassified splice variants.

Regiodivergent sp3 C-H Functionalization via Ni-Catalyzed Chain-Walking Reactions.

The catalytic translocation of a metal catalyst along a saturated hydrocarbon side chain constitutes a powerful strategy for enabling bond-forming reactions at remote, yet previously unfunctionalized, sp3 C-H sites. In recent years, Ni-catalyzed chain-walking reactions have offered counterintuitive strategies for forging sp3 architectures that would be difficult to accomplish otherwise. Although these strategies have evolved into mature tools for advanced organic synthesis, it was only recently that chemists showed the ability to control the motion at which the catalyst "walks" throughout the alkyl chain. Specialized ligand backbones, additives and a judicious choice of noninnocent functional groups on the side chain have allowed the design of "a la carte" protocols that enable regiodivergent bond-forming scenarios at different sp3 C-H sites with distinct topological surface areas. Given the inherent interest in increasing the fraction of sp3 hybridized carbons in medicinal chemistry, Ni-catalyzed regiodivergent chain-walking reactions might expedite the access to target leads in drug discovery campaigns.

Pre-freezing selection of Holstein bull semen with the BoviPure colloid as double- or single-layer centrifugation improves the post-thawing quality.

Artificial insemination (AI) is critical for breeding in the dairy industry. High-merit bulls can present low freezability, hampering genetic dissemination. Thawed semen can be improved using density gradient centrifugation (DGC) with colloids, but little information deals with the pre-freezing application. Thus, the BoviPure colloid (optimized for bull spermatozoa) was tested for pre-freezing application as the usual double-layer (DLC) versus single-layer (SLC, quick and economical). Semen from twelve Holstein-Friesian bulls was extended with OPTIXcell extender, frozen (Control), or processed by SLC or DLC and frozen. Sperm were assessed pre-freezing for motility and viability and post-thawing (directly and after 4 h 38 °C) for apoptosis, capacitation status, acrosomal damage, mitochondrial activity, cytoplasmic and mitochondrial reactive oxygen species (ROS), and chromatin status (SCSA for DNA fragmentation and chromatin compaction and monobromobimane, mBBr, for disulfide bridges evaluation). The DGC improved parameters post-thawing (e.g., 57.5%±10.1 motility vs. control 53.3% ± 11.2) at the cost of sperm loss (sperm recovery of DGC 14.4% ± 2.5 and SLC 17.4% ± 2.5). DNA fragmentation (%DFI) decreased (0.21% ± 0.53 vs. control 1.30% ± 0.10), and SLC reduced chromatin compaction. A clustering procedure separated lesser (LF) and greater freezability (GF) bulls. LF samples were especially benefited by DGC, with SLC providing better post-thawing results for this group. In conclusion, pre-freezing DGC improved sperm parameters post-thawing, potentially improving the cryopreservation of low-freezability semen from high-merit bulls. SLC, quicker and economical, would be preferable since it showed similar or higher performance than DLC.

Cardiac Progenitor Cell Exosomal miR-935 Protects against Oxidative Stress.

Oxidative stress-induced myocardial apoptosis and necrosis are critically involved in ischemic infarction, and several sources of extracellular vesicles appear to be enriched in therapeutic activities. The central objective was to identify and validate the differential exosome miRNA repertoire in human cardiac progenitor cells (CPC). CPC exosomes were first analyzed by LC-MS/MS and compared by RNAseq with exomes of human mesenchymal stromal cells and human fibroblasts to define their differential exosome miRNA repertoire (exo-miRSEL). Proteomics demonstrated a highly significant representation of cardiovascular development functions and angiogenesis in CPC exosomes, and RNAseq analysis yielded about 350 different miRNAs; among the exo-miRSEL population, miR-935 was confirmed as the miRNA most significantly up-regulated; interestingly, miR-935 was also found to be preferentially expressed in mouse primary cardiac Bmi1+high CPC, a population highly enriched in progenitors. Furthermore, it was found that transfection of an miR-935 antagomiR combined with oxidative stress treatment provoked a significant increment both in apoptotic and necrotic populations, whereas transfection of a miR-935 mimic did not modify the response. Conclusion. miR-935 is a highly differentially expressed miRNA in exo-miRSEL, and its expression reduction promotes oxidative stress-associated apoptosis. MiR-935, together with other exosomal miRNA members, could counteract oxidative stress-related apoptosis, at least in CPC surroundings.

Comproportionation and disproportionation in nickel and copper complexes.

Disproportionation and comproportionation reactions have become increasingly important electron transfer events in organometallic chemistry and catalysis. The renewed interest in these reactions is in part attributed to the improved understanding of first-row metals and their ability to occupy odd and even oxidation states. Disproportionation and comproportionation reactions enable metal complexes to shuttle between various oxidation states, a matter of utmost relevance for controlling the speciation and catalytic turnover. In addition, these reactions have a direct impact in the thermodynamic and kinetic stability of the corresponding metal complexes. This review covers the relevance and impact of these processes in electron transfer reactions and provides valuable information about their non-negligible influence in Ni- and Cu-catalysed transformations.

C(sp2)-H Hydroxylation via Catalytic 1,4-Ni Migration with N2O.

Herein, we report a Ni-catalyzed C(sp2)-H hydroxylation of aryl bromides with N2O as an oxygen-atom donor. The reaction is enabled by a 1,4-Ni translocation that results in ipso/ortho difunctionalized products. Regioselectivity and stereocontrol are dictated by a judicious choice of the ligand backbone, thus giving access to either carbonyl or phenol derivatives and offering an opportunity to repurpose hazardous substances en route to valuable oxygen-containing building blocks.

α-Difluoroalkylation of Benzyl Amines with Trifluoromethylarenes.

An α-difluoroalkylation of benzyl amines with trifluoromethylarenes is disclosed herein. This protocol is characterized by its operational simplicity, excellent chemoselectivity and broad scope-even with advanced synthetic intermediates-, thus offering a new entry point to medicinally-relevant α-difluoroalkylated amines from simple, yet readily accessible, precursors.