Chronic sacroiliac joint dysfunction and CT-guided percutaneous fixation: a 6-year experience.

PURPOSE: Reporting the clinical outcomes, patient satisfaction, and complications following an imaging-guided percutaneous screw fixation in the treatment of sacroiliac joint dysfunction and evaluating the safety and effectiveness of this method. METHODS: We performed a retrospective study on a prospectively gathered cohort of patients with physiotherapy-resistant pain due to sacroiliac joint incompetence that underwent percutaneous screw fixation, between 2016 and 2022 in our center. A minimum of two screws were used in all patients to obtain fixation of the sacroiliac joint, using percutaneous screw insertion under CT guidance, coupled with a C-arm fluoroscopy unit. RESULTS: The mean visual analog scale significantly improved at 6 months of follow-up (p < 0.05). One hundred percent of the patients reported significant improvement in pain scores at the final follow-up. None of our patients experienced intraoperative or postoperative complications. CONCLUSION: The use of percutaneous sacroiliac screws provides a safe and effective technique for the treatment of sacroiliac joint dysfunction in patients with chronic resistant pain.

Synthesis of Functionalized Triblock Copolyesters Derived from Lactic Acid and Macrolactones for Bone Tissue Regeneration.

Synthetic and functional grafts are a great alternative to conventional grafts. They can provide a physical support and the precise signaling for cells to heal damaged tissues. In this study, a novel RGD peptide end-functionalized poly(ethylene glycol)-b-poly(lactic acid)-b-poly(globalide)-b-poly(lactic acid)-b-poly(ethylene glycol) (RGD-PEG-PLA-PGl-PLA-PEG-RGD) is synthetized and used to prepare functional scaffolds. The PGl inner block is obtained by enzymatic ring-opening polymerization of globalide. The outer PLA blocks are obtained by ring-opening polymerization of both, l-lactide or a racemic mixture, initiated by the α-ω-telechelic polymacrolactone. The presence of PGl inner block enhances the toughness of PLA-based scaffolds, with an increase of the elongation at break up to 300% when the longer block of PGl is used. PLA-PGl-PLA copolymer is coupled with α-ω-telechelic PEG diacids by esterification reaction. PEGylation provides hydrophilic scaffolds as the contact angle is reduced from 114° to 74.8°. That difference improves the contact between the scaffolds and the culture media. Moreover, the scaffolds are functionalized with RGD peptides at the surface significantly enhancing the adhesion and proliferation of bone marrow-derived primary mesenchymal stem cells and MC3T3-E1 cell lines in vitro. These results place this multifunctional polymer as a great candidate for the preparation of temporary grafts.

Wax worm saliva and the enzymes therein are the key to polyethylene degradation by Galleria mellonella.

Plastic degradation by biological systems with re-utilization of the by-products could be a future solution to the global threat of plastic waste accumulation. Here, we report that the saliva of Galleria mellonella larvae (wax worms) is capable of oxidizing and depolymerizing polyethylene (PE), one of the most produced and sturdy polyolefin-derived plastics. This effect is achieved after a few hours' exposure at room temperature under physiological conditions (neutral pH). The wax worm saliva can overcome the bottleneck step in PE biodegradation, namely the initial oxidation step. Within the saliva, we identify two enzymes, belonging to the phenol oxidase family, that can reproduce the same effect. To the best of our knowledge, these enzymes are the first animal enzymes with this capability, opening the way to potential solutions for plastic waste management through bio-recycling/up-cycling.

Heritable vaginal bacteria influence immune tolerance and relate to early-life markers of allergic sensitization in infancy.

Maternal asthma status, prenatal exposures, and infant gut microbiota perturbation are associated with heightened risk of atopy and asthma risk in childhood, observations hypothetically linked by intergenerational microbial transmission. Using maternal vaginal (n = 184) and paired infant stool (n = 172) samples, we identify four compositionally and functionally distinct Lactobacillus-dominated vaginal microbiota clusters (VCs) that relate to prenatal maternal health and exposures and infant serum immunoglobulin E (IgE) status at 1 year. Variance in bacteria shared between mother and infant pairs relate to VCs, maternal allergy/asthma status, and infant IgE levels. Heritable bacterial gene pathways associated with infant IgE include fatty acid synthesis and histamine and tryptophan degradation. In vitro, vertically transmitted Lactobacillus jensenii strains induce immunosuppressive phenotypes on human antigen-presenting cells. Murine supplementation with L. jensenii reduces lung eosinophils, neutrophilic expansion, and the proportion of interleukin-4 (IL-4)+ CD4+ T cells. Thus, bacterial and atopy heritability are intimately linked, suggesting a microbial component of intergenerational disease transmission.

Bioinspired gelatin/bioceramic composites loaded with bone morphogenetic protein-2 (BMP-2) promote osteoporotic bone repair.

There are currently several commercialized products approved by the Food and Drug Administration and the European Medicines Agency based on the use of recombinant human BMP-2 for the treatment of non-unions long fractures and spinal fusion. However, the adverse effects recorded with the use of BMPs suggest the need for drug delivery carriers that allow reducing the required doses and improve their cost-effectiveness. Herein, we have developed a new osteoconductive scaffold that reduces the required doses of BMP-2 for promoting bone regeneration in an osteoporotic defect model. The composite is, in brief, a gelatin-based 3D scaffold reinforced with either calcium sulfate or hydroxyapatite as an inorganic osteoconductive biomaterial. To this end, the organic/inorganic composite systems showed high hydration capacity and good in vitro degradability. The incorporation of 7.5% (m/v) ceramic compounds resulted in scaffolds with stiffer Young modulus (179 and 75 kPa for CaSO4_7 and HA_7, respectively) than bare gelatin hydrogels (48 kPa). Studies with human bone-marrow derived mesenchymal stem cells (hBM-MSCs) revealed that the 3D scaffolds promote cell adhesion and proliferation along with osteogenic differentiation capabilities. Specifically, downregulation of stemness (Nanog, Oct4) genes and upregulation of osteogenic markers (ALP, Col1a1, Fmod) by two fold were observed over 10 days under basal culture conditions. Promisingly, the sustained in vitro release of BMP-2 observed from the porous reinforced scaffolds allowed us to address the critical-sized osteoporotic mice calvarial defects with a relatively low growth factor doses (600 ng BMP-2/scaffold) compared to conventional doses at 2-15 micrograms. Overall, this study demonstrates the promising potential of osteoconductive gelatin/calcium bioceramics composites as osteogenic growth factors delivery carriers for bone-regeneration via ultra-low growth factor doses.

Single-Cell Mapping of Progressive Fetal-to-Adult Transition in Human Naive T Cells.

Whereas the human fetal immune system is poised to generate immune tolerance and suppress inflammation in utero, an adult-like immune system emerges to orchestrate anti-pathogen immune responses in post-natal life. It has been posited that cells of the adult immune system arise as a discrete ontological "layer" of hematopoietic stem-progenitor cells (HSPCs) and their progeny; evidence supporting this model in humans has, however, been inconclusive. Here, we combine bulk and single-cell transcriptional profiling of lymphoid cells, myeloid cells, and HSPCs from fetal, perinatal, and adult developmental stages to demonstrate that the fetal-to-adult transition occurs progressively along a continuum of maturity-with a substantial degree of inter-individual variation at the time of birth-rather than via a transition between discrete waves. These findings have important implications for the design of strategies for prophylaxis against infection in the newborn and for the use of umbilical cord blood (UCB) in the setting of transplantation.

Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells.

T cell receptor (TCR) stimulation and cytokine cues drive the differentiation of CD4+ naïve T cells into effector T cell populations with distinct proinflammatory or regulatory functions. Unlike adult naïve T cells, human fetal naïve CD4+ T cells preferentially differentiate into FOXP3+ regulatory T (Treg) cells upon TCR activation independent of exogenous cytokine signaling. This cell-intrinsic predisposition for Treg differentiation is implicated in the generation of tolerance in utero; however, the underlying mechanisms remain largely unknown. Here, we identify epigenetic and transcriptional programs shared between fetal naïve T and committed Treg cells that are inactive in adult naïve T cells and show that fetal-derived induced Treg (iTreg) cells retain this transcriptional program. We show that a subset of Treg-specific enhancers is accessible in fetal naïve T cells, including two active superenhancers at Helios Helios is expressed in fetal naïve T cells but not in adult naïve T cells, and fetal iTreg cells maintain Helios expression. CRISPR-Cas9 ablation of Helios in fetal naïve T cells impaired their differentiation into iTreg cells upon TCR stimulation, reduced expression of immunosuppressive genes in fetal iTreg cells such as IL10, and increased expression of proinflammatory genes including IFNG Consequently, Helios knockout fetal iTreg cells had reduced IL-10 and increased IFN-γ cytokine production. Together, our results reveal important roles for Helios in enhancing preferential fetal Treg differentiation and fine-tuning eventual Treg function. The Treg-biased programs identified within fetal naïve T cells could potentially be used to engineer enhanced iTreg populations for adoptive cellular therapies.

CD161 contributes to prenatal immune suppression of IFNγ-producing PLZF+ T cells.

BACKGROUND: While the human fetal immune system defaults to a program of tolerance, there is concurrent need for protective immunity to meet the antigenic challenges encountered after birth. Activation of T cells in utero is associated with the fetal inflammatory response with broad implications for the health of the fetus and of the pregnancy. However, the characteristics of the fetal effector T cells that contribute to this process are largely unknown. METHODS: We analyzed primary human fetal lymphoid and mucosal tissues and performed phenotypic, functional, and transcriptional analysis to identify T cells with pro-inflammatory potential. The frequency and function of fetal-specific effector T cells was assessed in the cord blood of infants with localized and systemic inflammatory pathologies and compared to healthy term controls. RESULTS: We identified a transcriptionally distinct population of CD4+ T cells characterized by expression of the transcription factor Promyelocytic Leukemia Zinc Finger (PLZF). PLZF+ CD4+ T cells were specifically enriched in the fetal intestine, possessed an effector memory phenotype, and rapidly produced pro-inflammatory cytokines. Engagement of the C-type lectin CD161 on these cells inhibited TCR-dependent production of IFNγ in a fetal-specific manner. IFNγ-producing PLZF+ CD4+ T cells were enriched in the cord blood of infants with gastroschisis, a natural model of chronic inflammation originating from the intestine, as well as in preterm birth, suggesting these cells contribute to fetal systemic immune activation. CONCLUSION: Our work reveals a fetal-specific program of protective immunity whose dysregulation is associated with fetal and neonatal inflammatory pathologies.

LRP5 gene polymorphisms and radiographic joint damage in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is characterized by increased bone resorption and impaired bone formation. Osteoblast function is regulated by the canonical LRP5/Wnt/ß-catenin pathway. Bone mineral density and RA joint destruction are partially inherited. In line with this, we found significant associations between LRP5 SNPs (p.A1330V, p.N740N, p.V667M) and RA radiographic damage severity. INTRODUCTION: Increased bone resorption and impaired bone formation characterize rheumatoid arthritis (RA). Canonical Wnt/ß-catenin pathway, signalled by lipoprotein receptor-related protein-5 (LRP5), regulates osteoblast function. Since bone mineral density (BMD) and RA joint destruction are partially inherited, we studied their association with LRP5 single nucleotide polymorphisms (SNPs). METHODS: Clinical data and peripheral blood for biomarkers assessment and LRP5 genotyping were collected from 208 RA patients. Hands and feet X-rays were scored [modified Sharp/van der Heijde Score (SHS), joint space narrowing (JSN), and erosion scores]. Lumbar spine, total left proximal femur, and left hand BMD were assessed by dual-energy X-ray absorptiometry (DXA). RESULTS: TT genotypes for p.A1330V and p.N740N LRP5 SNPs associated with total SHS, erosion score, and hands erosion score; the same for p.A1330V with feet JSN score and p.N740N with hands total score. AG genotype for p.V667M associated with sclerostin and hands JSN score. Femoral BMD associated with TC genotype for p.N740N. Multiple test correction precluded a few of these associations. Among V667M-N740N-A1330V haplotypes: GTT associated with higher feet JSN score (OR = 3.80; p = 0.016) and ATT with higher JSN score (OR = 4.60; p = 0.032), hands total score (OR = 5.65; p = 0.022), and total SHS (OR = 6.74; p = 0.024). CONCLUSION: Significant associations between LRP5 SNPs (p.A1330V, p.N740N, and p.V667M) and the severity of radiographic damage reinforce the evidence of bone destruction heritability in RA.

A fatal gastric perforation secondary to ulcerated metastasis in undiagnosed breast cancer: pathological aspects and review of literature.

The authors describe a fatal case of gastric perforation secondary to an ulcerated metastasis in a woman with undiagnosed breast cancer. The 48-year-old woman, with no significant medical history, presented with weight loss, persistent dyspepsia and pain in the epigastric and mesogastric region. She was treated by her primary care physician with proton-pump inhibitors and antispasmodics. The following day she was found dead at her home. External examination showed a tumefaction in the lateral region of her left breast, near the axilla. Autopsy revealed 1000 ml of turbid, light-brown peritoneal fluid in the abdominal cavity and a perforated gastric wall. Histological examination of the breast mass showed an infiltrating, poorly-differentiated breast carcinoma. Microscopical analysis of the stomach wall revealed a perforated metastatic gastric ulcer. Immunohistochemistry was required to confirm the neoplastic involvement of the stomach due to metastatic breast cancer.

Challenges of evaluating a computer-based educational programme for women diagnosed with early-stage breast cancer: a randomised controlled trial.

In a two-group, multi-centre, randomised controlled 9 months trial, we (1) evaluated the impact of a computer-based educational programme compared to standard care and (2) examined whether different patterns of programme usage could be explained by demographic, medical and psychosocial factors. We involved 226 Swedish-speaking women diagnosed with early-stage breast cancer and scheduled for surgery. Primary outcomes were health self-efficacy and health care participation measured by the Comprehensive Health Enhancement Supportive System instrument. Secondary outcomes were anxiety and depression levels measured by the Hospital Anxiety and Depression scale. The Functional Assessment of Cancer Therapy-Breast and Sense of Coherence scales measured psychosocial factors for the study's secondary aim. Multi-level modelling revealed no statistically significant impact of the computer-based educational programme over time on the outcomes. Subsequent exploratory regression analysis revealed that older women with axillary dissection and increased physical well-being were more likely to use the programme. Furthermore, receiving post-operative chemotherapy and increased meaningfulness decreased the likelihood of use. Providing reliable and evidence-based medical and rehabilitation information via a computer-based programme might not be enough to influence multi-dimensional outcomes in women diagnosed with breast cancer. The use of these programmes should be further explored to promote adherence to e-Health supportive interventions.

"Retronychia--clinical and pathophysiological aspects".

Retronychia represents proximal ingrowth of the nail that occurs when the nail embeds backwards into the proximal nail fold. It is suspected when there is a persistent paronychia, particularly in the setting of trauma. Important clinical criteria for diagnosis are inflammation of the proximal nail fold, granulation tissue emerging from under the nail fold, thickening of the proximal portion of the nail plate and interruption of nail growth. The condition is rarely diagnosed and often misinterpreted, and is therefore unnecessarily treated with systemic antibiotics and antifungals. Avulsion of the nail confirms the diagnosis and it is the curative treatment. Conservative treatment with an adhesive technique is a valid option in early cases. We report 20 cases of retronychia diagnosed in our department between 2010 and 2013.

Application of age estimation methods based on teeth eruption: how easy is Olze method to use?

The development of new methods for age estimation has become with time an urgent issue because of the increasing immigration, in order to estimate accurately the age of those subjects who lack valid identity documents. Methods of age estimation are divided in skeletal and dental ones, and among the latter, Olze's method is one of the most recent, since it was introduced in 2010 with the aim to identify the legal age of 18 and 21 years by evaluating the different stages of development of the periodontal ligament of the third molars with closed root apices. The present study aims at verifying the applicability of the method to the daily forensic practice, with special focus on the interobserver repeatability. Olze's method was applied by three different observers (two physicians and one dentist without a specific training in Olze's method) to 61 orthopantomograms from subjects of mixed ethnicity aged between 16 and 51 years. The analysis took into consideration the lower third molars. The results provided by the different observers were then compared in order to verify the interobserver error. Results showed that interobserver error varies between 43 and 57 % for the right lower third molar (M48) and between 23 and 49 % for the left lower third molar (M38). Chi-square test did not show significant differences according to the side of teeth and type of professional figure. The results prove that Olze's method is not easy to apply when used by not adequately trained personnel, because of an intrinsic interobserver error. Since it is however a crucial method in age determination, it should be used only by experienced observers after an intensive and specific training.

Retrospective study of the medium-chain acyl-CoA dehydrogenase deficiency in Portugal.

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the commonest genetic defect of mitochondrial fatty acid ß-oxidation. About 60% of MCADD patients are homozygous for the c.985A>G (p.Lys329Glu) mutation in the ACADM gene (G985 allele). Herein, we present the first report on the molecular and biochemical spectrum of Portuguese MCADD population. From the 109 patients studied, 83 were diagnosed after inclusion of MCADD in the national newborn screening, 8 following the onset of symptoms and 18 through segregation studies. Gypsy ancestry was identified in 85/109 patients. The G985 allele was found in homozygosity in 102/109 patients, in compound heterozygosity in 6/109 and was absent in one patient. Segregation studies in the Gypsy families showed that 93/123 relatives were carriers of the G985 allele, suggesting its high prevalence in this ethnic group. Additionally, three new substitutions-c.218A>G (p.Tyr73Cys), c.503A>T (p.Asp168Val) and c.1205G>T (p.Gly402Val)-were identified. Despite the particularity of the MCADD population investigated, the G985 allele was found in linkage disequilibrium with H1(112) haplotype. Furthermore, two novel haplotypes, H5(212) and H6(122) were revealed.

Estereolitografía en Cirugía Maxilofacial / Stereolithography in maxillofacial surgery

Objetivo de la revisión: Es mostrar a la comunidad odontológica especialmente a la especialidad de cirugía maxilofacial, una herramienta valiosa y moderna, la estereolitografía como ayuda importante en la planificación y tratamiento en los diversos campos que desarrolla esta especialidad. Métodos: Se revisó la literatura en diversos buscadores y se seleccionó aquellos artículos que tienen relación con el tema. Resultados: Se encontró literatura valiosa que describe con claridad ¨cómo la estereotlitografía es una herramienta de ayuda en la planificación del tratamiento en las diversa  áreas de la cirugía maxilofacial. Conclusión: En la cirugía contempor nea el advenimiento de las innovaciones.

Objective of the review: Is to show the dental community especially the specialty of maxillofacial surgery, a valuable and modern tool, stereolithography as important in treatment planning and in the various fields that help develop this specialty. Methods: Literature was reviewed in various search engines and articles that are related to the selected topic. Results: Valuable literature that clearly describes how the estereotlitograf¡a is a tool to aid in treatment planning in different areas of the maxillofacial surgery was found. Conclusion: In contemporary surgery the advent of innovations.

Unusual coexistence of opportunistic lung infections in a human immunodeficiency virus positive patient suffering from persistent Pneumocystis jirovecii pneumonia: a case report.

It is well established that HIV patients are at high risk of opportunistic infections (OI), like the ones caused by Pneumocystis jirovecii, a worldwide pathogen implicated in interstitial pneumonia (PcP). We present a case of a newly diagnosed HIV-1 patient with multiple OI, including a persistent form of PcP, an invasive aspergillosis (IA), cytomegalovirus and Mycobacterium xenopi lung infection. We describe the combination of laboratorial screening, surgery and antimicrobial therapy that were crucial for patient recovery.

Perfil dos usuários em Assistência Domiciliar no SUS – Coordenadoria Regional de Saúde Sul da cidade de São Paulo / Profile of Home Care users in the SUS - Regional Health south of the city of Sao Paulo

A incidência de usuários com dependência para a realização das atividades de vida diária (AVD) é crescente e tem sido regulamentada pelo Ministério da Saúde desde 2002. Essa população deve ser atendida no ambiente domiciliar buscando melhor conforto e segurança. Na região sul do município de São Paulo, esse atendimento é realizado pela atenção básica, por equipes de assistência domiciliar (UAD) e unidades básicas de saúde (UBS/ESF) que acompanham os pacientes crônicos acamados estáveis, em domicílio, com suporte das UAD(AU)

Perfil dos usuários em Assistência Domiciliar no SUS – Coordenadoria Regional de Saúde Sul da cidade de São Paulo

A incidência de usuários com dependência para a realização das atividades de vida diária (AVD) é crescente e tem sido regulamentada pelo Ministério da Saúde desde 2002. Essa população deve ser atendida no ambiente domiciliar buscando melhor conforto e segurança. Na região sul do município de São Paulo, esse atendimento é realizado pela atenção básica, por equipes de assistência domiciliar (UAD) e unidades básicas de saúde (UBS/ESF) que acompanham os pacientes crônicos acamados estáveis, em domicílio, com suporte das UAD

Perfil dos usuários em assistência domiciliar no SUS: coordenadoria regional de saúde sul da cidade de São Paulo / Profile of home care users in the SUS: regional health south of the city of Sao Paulo

A incidência de usuários com dependência para a realização das atividades de vida diária (AVD) é crescente e tem sido regulamentada pelo Ministério da Saúde desde 2002. Essa população deve ser atendida no ambiente domiciliar buscando melhor conforto e segurança. Na região sul do município de São Paulo, esse atendimento é realizado pela atenção básica, por equipes de assistência domiciliar (UAD) e unidades básicas de saúde (UBS/ESF) que acompanham os pacientes crônicos acamados estáveis, em domicílio, com suporte das UAD.

Hansen's disease mimicking a systemic vasculitis.

Hansen's disease, caused by Mycobacterium leprae, classically presents with cutaneous and neurological manifestations. Rheumatologic manifestations present in 1 to 5% of the patients, and include arthritis, arthralgias, Charcot arthropathy, erythema nodosum and vasculitis. We report a case of a 86 year old woman with polyarthritis, subcutaneous nodules and leg ulcers whose differential diagnosis included primary vasculitis and diffuse connective tissue diseases and ended to be leprosy in a non endemic country.