Fully Automated Measurement of the Insall-Salvati Ratio with Artificial Intelligence.

Patella alta (PA) and patella baja (PB) affect 1-2% of the world population, but are often underreported, leading to potential complications like osteoarthritis. The Insall-Salvati ratio (ISR) is commonly used to diagnose patellar height abnormalities. Artificial intelligence (AI) keypoint models show promising accuracy in measuring and detecting these abnormalities.An AI keypoint model is developed and validated to study the Insall-Salvati ratio on a random population sample of lateral knee radiographs. A keypoint model was trained and internally validated with 689 lateral knee radiographs from five sites in a multi-hospital urban healthcare system after IRB approval. A total of 116 lateral knee radiographs from a sixth site were used for external validation. Distance error (mm), Pearson correlation, and Bland-Altman plots were used to evaluate model performance. On a random sample of 2647 different lateral knee radiographs, mean and standard deviation were used to calculate the normal distribution of ISR. A keypoint detection model had mean distance error of 2.57 ± 2.44 mm on internal validation data and 2.73 ± 2.86 mm on external validation data. Pearson correlation between labeled and predicted Insall-Salvati ratios was 0.82 [95% CI 0.76-0.86] on internal validation and 0.75 [0.66-0.82] on external validation. For the population sample of 2647 patients, there was mean ISR of 1.11 ± 0.21. Patellar height abnormalities were underreported in radiology reports from the population sample. AI keypoint models consistently measure ISR on knee radiographs. Future models can enable radiologists to study musculoskeletal measurements on larger population samples and enhance our understanding of normal and abnormal ranges.

Factors increasing the risk for a severe reaction in anaphylaxis: An analysis of data from The European Anaphylaxis Registry.

BACKGROUND: Preventive measures to decrease the frequency and intensity of anaphylactic events are essential to provide optimal care for allergic patients. Aggravating factors may trigger or increase the severity of anaphylaxis and therefore need to be recognized and avoided. OBJECTIVE: To identify and prioritize factors associated with an increased risk of developing severe anaphylaxis. METHODS: Data from the Anaphylaxis Registry (122 centers in 11 European countries) were used in logistic regression models considering existing severity grading systems, elicitors, and symptoms to identify the relative risk of factors on the severity of anaphylaxis. RESULTS: We identified higher age and concomitant mastocytosis (OR: 3.1, CI: 2.6-3.7) as the most important predictors for an increased risk of severe anaphylaxis. Vigorous physical exercise (OR: 1.5, CI: 1.3-1.7), male sex (OR: 1.2, CI: 1.1-1.3), and psychological burden (OR: 1.4, CI: 1.2-1.6) were more often associated with severe reactions. Additionally, intake of beta-blockers (OR: 1.9, CI: 1.5-2.2) and ACE-I (OR: 1.28, CI: 1.05, 1.51) in temporal proximity to allergen exposition was identified as an important factor in logistic regression analysis. CONCLUSION: Our data suggest it may be possible to identify patients who require intensified preventive measures due to their relatively higher risk for severe anaphylaxis by considering endogenous and exogenous factors.

Augmentation of hepatitis C virus-specific immunity and sustained virologic response.

Treatment for chronic hepatitis C virus (HCV) infection has rapidly evolved into interferon-free directly acting antiviral regimens (DAA) that result in high sustained virologic response. DAAs primarily work by suppressing HCV replication and rely less on the immune system than interferon-based therapies. However, it is unclear whether the immune system recovers with suppression of HCV replication and contributes to HCV clearance with DAA therapy. We previously demonstrated HCV clearance is associated with increased HCV-specific immunity in CHCV-GT-1-infected patients during treatment with sofosbuvir (SOF)+ribavirin (RBV). Here, we aimed to analyse changes in HCV-specific immunological responses associated with viral clearance with combination DAA therapy of SOF+ledipasvir (LDV) for 12 weeks in CHCV-GT1 (N=14) patients who relapsed without augmentation of HCV-specific immunity during treatment with SOF+RBV. Phenotypic and functional changes within the T-cell compartment of PBMCs pre- and post-treatment were analysed. Retreatment of relapsers with LDV/SOF resulted in all patients attaining SVR12 . Suppression of HCV was associated with a decline in T-cell exhaustion markers (CD57; Tim3; PD1) along with augmented of HCV-specific T-cell IFN-gamma responses post-treatment. Addition of LDV to SOF was associated with augmentation of HCV-specific immunity and SVR in patients who previously failed SOF+RBV therapy without increased immunity. These findings demonstrate a novel effect of DAA in inducing host immune responses to aid HCV clearance and achieve SVR.

Achieving sustained virologic response after interferon-free hepatitis C virus treatment correlates with hepatic interferon gene expression changes independent of cirrhosis.

Chronic hepatitis C virus (HCV) infection can now be treated with oral directly acting antiviral agents, either with or without ribavirin (RBV). Virologic relapse after treatment can occur, and in some studies was more common in cirrhotic subjects. We previously observed changes in hepatic immunity during interferon (IFN)-free therapy that correlated with favourable outcome in subjects with early liver disease. Here, we compared changes in endogenous IFN pathways during IFN-free, RBV-free therapy between cirrhotic and noncirrhotic subjects. mRNA and microRNA (miRNA) expression analyses were performed on paired pre- and post-treatment liver biopsies from genotype-1 HCV subjects treated with sofosbuvir/ledipasvir (SOF/LDV) for 12 weeks (n = 4, 3 cirrhotics) or SOF/LDV combined with GS-9669 or GS-9451 for 6 weeks (n = 6, 0 cirrhotics). Nine of ten subjects achieved a sustained virologic response (SVR), while one noncirrhotic subject relapsed. Hepatic IFN-stimulated gene expression decreased with treatment in the liver of all subjects, with no observable impact of cirrhosis. Hepatic gene expression of type III IFNs (IFNL1, IFNL3, IFNL4-ΔG) similarly decreased with treatment, while IFNA2 expression, undetectable in all subjects pretreatment, was detected post-treatment in three subjects who achieved a SVR. Only the subject who relapsed had detectable IFNL4-ΔG expression in post-treatment liver. Other IFNs had no change in gene expression (IFNG, IFNB1, IFNA5) or could not be detected. Although expression of multiple hepatic miRNAs changed with treatment, many miRNAs previously implicated in HCV replication and IFN signalling had unchanged expression. In conclusion, favourable treatment outcome during IFN-free HCV therapy is associated with changes in the host IFN response regardless of cirrhosis.

Oral epithelial cells and their interactions with HIV-1.

As the AIDS pandemic has continued, our understanding of the events that occur during the entry and infection of conventional, susceptible cells has increased dramatically, leading to the development of control therapies for HIV-infected individuals. However, an ongoing hole in our understanding is how HIV crosses the mucosal barriers to gain access to permissive cells, despite how important this information would be in developing successful vaccines and other preventative measures such as topical anti-HIV microbicides. In particular, our knowledge of the role that epithelial cells of the mucosal surfaces play in infection - both during early phases and throughout the life of an infected individual, is currently hazy at best. However, several studies in recent years suggest that HIV can bind to and traverse these mucosal epithelial cells, providing a reservoir of infection that can subsequently infect underlying permissive cells. Despite this interaction with epithelial cells, evidence suggests HIV-1 does not productively infect these cells, although they are capable of transferring surface-bound and transcytosed virus to other, permissive cells. Further, there appear to be key differences between adult and infant epithelial cells in the degree to which HIV can transcytose and infect the epithelium. Thus, it is clear that, whilst not primary targets for infection and virus replication, epithelial cells play an important role in the infection cycle and improving our understanding of their interactions with HIV could potentially provide key insights necessary to develop effective preventative therapies.

Effect of co-morbid depression on neurocognitive functioning in patients with obsessive-compulsive disorder: a study from India.

OBJECTIVE: To study neuropsychological function in subjects with obsessive-compulsive disorder (OCD) with and without co-morbid depression in comparison with healthy controls (HC). METHODS: The 3 sample groups included subjects with OCD without depression (OCD group, n = 30); subjects with OCD and depression (OCDD group, n = 20); and HC (n = 25). All 3 groups were matched for age, gender, and years of education, and they were assessed on the following: Trail Making Tests A and B, Verbal Fluency Test, PGI Memory Scale, Stroop test, Tower of London Test, Raven's Standard Progressive Matrices, Wisconsin Card Sorting Test, and the Object Alternation Test. RESULTS: Both OCD and OCDD groups performed more poorly than HC, whereas the OCDD group performed worse than OCD group. Besides, OCD and OCDD groups had significantly poorer performance on tests of attention, memory, executive functions, verbal fluency, and intelligence. The OCDD group performed worse than the OCD group notably on Verbal Fluency Test, PGI memory test, and Object Alternation Test. CONCLUSION: On tests of neurocognitive functioning, the performance of the OCDD group was poorer than the OCD group, and both performed poorer than HC, suggesting that OCD is associated with neurocognitive dysfunction and that this is exacerbated in the presence of depression.

Childhood exposure to ambient polycyclic aromatic hydrocarbons is linked to epigenetic modifications and impaired systemic immunity in T cells.

BACKGROUND: Evidence suggests that exposure to polycyclic aromatic hydrocarbons (PAHs) increases atopy; it is unclear how PAH exposure is linked to increased severity of atopic diseases. OBJECTIVE: We hypothesized that ambient PAH exposure is linked to impairment of immunity in atopic children (defined as children with asthma and/or allergic rhinitis) from Fresno, California, an area with elevated ambient PAHs. METHODS: We recruited 256 subjects from Fresno, CA. Ambient PAH concentrations (ng/m(3) ) were measured using a spatial-temporal regression model over multiple time periods. Asthma diagnosis was determined by current NHLBI criteria. Phenotyping and functional immune measurements were performed from isolated cells. For epigenetic measurements, DNA was isolated and pyrosequenced. RESULTS: We show that higher average PAH exposure was significantly associated with impaired Treg function and increased methylation in the forkhead box protein 3 (FOXP3) locus (P < 0.05), conditional on atopic status. These epigenetic modifications were significantly linked to differential protein expression of FOXP3 (P < 0.001). Methylation was associated with cellular functional changes, specifically Treg dysfunction, and an increase in total plasma IgE levels. Protein expression of IL-10 decreased and IFN-γ increased as the extent of PAH exposure increased. The strength of the associations generally increased as the time window for average PAH exposure increased from 24 hr to 1 year, suggesting more of a chronic response. Significant associations with chronic PAH exposure and immune outcomes were also observed in subjects with allergic rhinitis. CONCLUSIONS AND CLINICAL RELEVANCE: Collectively, these results demonstrate that increased ambient PAH exposure is associated with impaired systemic immunity and epigenetic modifications in a key locus involved in atopy: FOXP3, with a higher impact on atopic children. The results suggest that increased atopic clinical symptoms in children could be linked to increased PAH exposure in air pollution.

Clinical relevance is associated with allergen-specific wheal size in skin prick testing.

BACKGROUND: Within a large prospective study, the Global Asthma and Allergy European Network (GA(2) LEN) has collected skin prick test (SPT) data throughout Europe to make recommendations for SPT in clinical settings. OBJECTIVE: To improve clinical interpretation of SPT results for inhalant allergens by providing quantitative decision points. METHODS: The GA(2) LEN SPT study with 3068 valid data sets was used to investigate the relationship between SPT results and patient-reported clinical relevance for each of the 18 inhalant allergens as well as SPT wheal size and physician-diagnosed allergy (rhinitis, asthma, atopic dermatitis, food allergy). The effects of age, gender, and geographical area on SPT results were assessed. For each allergen, the wheal size in mm with an 80% positive predictive value (PPV) for being clinically relevant was calculated. RESULTS: Depending on the allergen, from 40% (blatella) to 87-89% (grass, mites) of the positive SPT reactions (wheal size ≥ 3 mm) were associated with patient-reported clinical symptoms when exposed to the respective allergen. The risk of allergic symptoms increased significantly with larger wheal sizes for 17 of the 18 allergens tested. Children with positive SPT reactions had a smaller risk of sensitizations being clinically relevant compared with adults. The 80% PPV varied from 3 to 10 mm depending on the allergen. CONCLUSION: These 'reading keys' for 18 inhalant allergens can help interpret SPT results with respect to their clinical significance. A SPT form with the standard allergens including mm decision points for each allergen is offered for clinical use.

Distinct and overlapping genomic profiles and antiviral effects of Interferon-λ and -α on HCV-infected and noninfected hepatoma cells.

Recently, several SNPs in the region of the IL28B (IFN-λ) gene have been associated with spontaneous clearance of hepatitis C virus (HCV) and enhanced cure rates for IFN-alfa-based therapies, suggesting a potential correlation between IFN-λ and the ability to clear HCV. To understand the mechanism of IFN-λ's as compared to IFN-α's antiviral activity, we performed a comprehensive analysis of their anti-HCV effects, whole genome transcriptome profiling with validation, and signalling of IFN-α and IFN-λ using J6/JFH-1 and Huh7.5 cells in vitro. IFN-λ and IFN-α exhibited comparable anti-HCV activity and gene expression profiles in Huh7.5 cells. While the majority of genes induced by IFN-α and IFN-λ were similar, IFN-λ exhibits profound, but delayed kinetics of IFN-stimulated genes (ISG) induction, while IFN-α induced more rapid induction of ISGs. Furthermore, the increased induction of ISG expression by IFN-λ correlated with up-regulation of IFN-λ receptor (IL-28RA) expression and more prolonged activation of the Jak-STAT signalling pathway. The findings from our comparative analysis of IFN-α and IFN-λ in HCV-infected and noninfected cells support the clinical use of IFN-λ as a potential alternative to IFN-α in the treatment of chronic hepatitis C.

Micrometric measurement of the density of stained odontoblast processes

The embryological, structural and functional unit of the dentine-pulp complex shares the odontoblast, located in the border of the dentine pulp, with basal nuclei and organelles. The odontoblast process emerges from its apical pole. It is formed by microtubules, microfilaments and vesicles covered by membranes penetrating the dentinal tubules, isolated from the inter-tubular matrix, along the extent of the dentine. The objective of this study was to evaluate the efficacy of three staining techniques: hematoxylin-eosin, periodic acid-Schiff and Schmorl, by staining the process, from beginning to end, and compare the results with the erosion technique. Thirty human teeth were employed in the trial; after their extraction the pulp was fixated, the pieces demineralized in nitric acid at 8%, the collagen filaments eliminated with Type II Collagenase, the tissue was stained, and the measurements were made. The portions with no pulp were prepared with the erosion technique. Results: Comparing the best results obtained by staining with the values obtained with the erosion technique, the former showed lower values. Conclusion: Staining techniques show lower density of the staining processes compared with the dentinal tubules in the erosion technique

Micrometric measurement of the density of stained odontoblast processes

The embryological, structural and functional unit of the dentine-pulp complex shares the odontoblast, located in the border of the dentine pulp, with basal nuclei and organelles. The odontoblast process emerges from its apical pole. It is formed by microtubules, microfilaments and vesicles covered by membranes penetrating the dentinal tubules, isolated from the inter-tubular matrix, along the extent of the dentine. The objective of this study was to evaluate the efficacy of three staining techniques: hematoxylin-eosin, periodic acid-Schiff and Schmorl, by staining the process, from beginning to end, and compare the results with the erosion technique. Thirty human teeth were employed in the trial; after their extraction the pulp was fixated, the pieces demineralized in nitric acid at 8%, the collagen filaments eliminated with Type II Collagenase, the tissue was stained, and the measurements were made. The portions with no pulp were prepared with the erosion technique. Results: Comparing the best results obtained by staining with the values obtained with the erosion technique, the former showed lower values. Conclusion: Staining techniques show lower density of the staining processes compared with the dentinal tubules in the erosion technique

Innate immunity including epithelial and nonspecific host factors: workshop 1B.

The majority of HIV infections are initiated at mucosal sites. The oral mucosal tissue has been shown to be a potential route of entry in humans and primates. Whereas HIV RNA, proviral DNA, and infected cells are detected in the oral mucosa and saliva of infected individuals, it appears that the oral mucosa is not permissive for efficient HIV replication and therefore may differ in susceptibility to infection when compared to other mucosal sites. Since there is no definitive information regarding the fate of the HIV virion in mucosal epithelium, there is a pressing need to understand what occurs when the virus is in contact with this tissue, what mechanisms are in play to determine the outcome, and to what degree the mechanisms and outcomes differ between mucosal sites. Workshop 1B tackled 5 important questions to define current knowledge about epithelial cell-derived innate immune agents, commensal and endogenous pathogens, and epithelial cells and cells of the adaptive immune system and how they contribute to dissemination or resistance to HIV infection. Discovering factors that explain the differential susceptibility and resistance to HIV infection in mucosal sites will allow for the identification and development of novel protective strategies.

Dyggve melchior clausen syndrome.

Dyggve Melchior Clausen syndrome is a rare autosomal recessive disorder, characterized by progressive spondylo epi metaphyseal dysplasia associated with mental retardation. The clinical and radiological findings resembles Morquio disease at the onset of condition, which may hinder its diagnosis. Two siblings with chatacteristic clinical (progressive postnatal dwarfism and mental retardation) and radiological features (irregular lace-like appearance of the iliac crests) are reported.

Celiac disease associated with recurrent Guillain Barre syndrome.

Celiac disease is associated with multiple extraintestinal presentations, including bone disease, endocrine disorders and neurological deficits. We report a 9 year old girl with celiac disease presenting with recurrent Guillain Barre syndrome (third episode). There was no other clinical manifestation except for refractory iron deficiency anemia. Molecular mimicry explaining the association between these two disorders, is far more interesting.

Forearm IVRA, using 0.5% lidocaine in a dose of 1.5 mg/kg with ketorolac 0.15 mg/kg for hand and wrist surgeries.

AIM: Local anesthetic toxicity remains one of the most dreaded complications of the intravenous regional anesthesia (IVRA) technique. It results from the sudden release of a large amount of local anesthetic (LA) into the systemic circulation. This release can occur when the tourniquet deflates accidentally during the procedure or when it is deflated intentionally at the end of the procedure to terminate the anesthesia. The forearm tourniquet IVRA technique may offer distinct advantages over the conventional upper arm tourniquet IVRA technique. Use of a forearm tourniquet allows the dosage of local anesthetic to be decreased to almost half of what is required with an upper arm tourniquet, and the incidence of tourniquet pain has been reported to be less with forearm tourniquet. In this study, authors assessed the clinical efficacy of administering IVRA with lidocaine plus ketorolac using either a forearm or upper arm tourniquet. METHODS: Upper arm IVRA was established using 0.5% lidocaine at a dose of 3 mg/kg with ketorolac at 0.3 mg/kg. Forearm IVRA was established using 0.5 % lidocaine at a dose of 1.5 mg/kg with ketorolac at 0.15 mg/kg. Quality of surgical anesthesia, onset, duration of sensory block and postoperative surgical pain and analgesic use were recorded and assessed. The incidence of local anesthetic toxicity and local complications due to the tourniquet were also recorded. RESULTS: Surgical anesthesia was assessed as excellent or good (grade 0/1) in all 20/20 patients who received IVRA using an upper arm tourniquet and in 19/20 patients who received IVRA using a forearm tourniquet (P=1.00). Onset as well as regression of sensory block was similar in both the groups. Post operative VAS scores at 30 min and 60 min were statistically comparable between the two groups, as was the analgesic use in the first 24 h. CONCLUSIONS: In conclusion, forearm IVRA provides effective perioperative anesthesia and analgesia. The technique results in a similar clinical profile as upper arm IVRA while using half the dose of both lidocaine and ketorolac.

Estudio epidemiológico de la salud en Rosario

La población de mayores recursos de Rosario puede acceder a la atención privada, los sectores medios y carenciados se atienden con obras sociales y servicios públicos. Estos últimos carecen de programas para el cuidado oral de adultos realizando prioritariamente extracciones. El objetivo de este estudio fue conocer el grado de adhesión a cuidados para la conservación de piezas dentales en tres sub-poblaciones. Los concurrentes de 15-45 años fueron invitados a participar respondiendo una anamnesis estandarizada sobre: edad, sexo, tipo de servicio, índice CPO, tiempo transcurrido entre consultas y pieza extraída el día de la entrevista. En los servicios públicos hubo mayoría de piezas perdidas y en el privado de obturaciones. El tiempo transcurrido entre visitas fue menor en el privado (p=0.04) y la causa más frecuente fue por obturación, mientras que en los públicos lo fue por extracción (p=0.01). Las piezas mas extraídas fueron premolares y molares en todos los servicios.(AU)

Tibial torsion in non-arthritic Indian adults: a computer tomography study of 100 limbs.

BACKGROUND: Knowledge of normal tibial torsion is mandatory during total knee replacement (TKR), deformity correction and fracture management of tibia. Different values of tibial torsion have been found in different races due to biological and mechanical factors. Value of normal tibial torsion in Indian limbs is not known, hence this study to determine the norm of tibial torsional value in normal Indian population. MATERIALS AND METHODS: Computer tomography (CT) scans were performed in 100 non-arthritic limbs of 50 Indian adults (42 males, eight females; age 26-40 years). Value of tibial torsion was measured using dorsal tangent to tibial condyles proximally and bimalleolar axis distally. RESULTS: Normal tibial torsion was found to be 21.6 +/- 7.6 (range 4.8 to 39.5) with none of the values in internal rotation. Right tibia was externally rotated by 2 degrees as compared to the left side (P 0.029). No significant difference was found in male and female subjects. Value of tibial torsion was less than in Caucasian limbs, but was comparable to Japanese limbs when studies using similar measurement technique were compared. CONCLUSIONS: Indian limbs have less tibial torsion than Caucasian limbs but the value of tibial torsion is comparable to Japanese limbs.

Hábitos alimentarios y experiencia de caries en adultos jóvenes en Rosario Argentina / Food habits and caries experience in young adult from Rosario Argentina

En Rosario la atención odontológica se brinda en ámbitos privados y públicos. Los servicios públicos carecen de programas para evitar la pérdida dentaria en adultos. Nuestro objetivo fue describir el perfil epidemiológico de experiencia de caries y hábitos dietéticos en tres sub-poblaciones de adultos jóvenes. Aplicando una anamnesis estandarizada se investigaron 517 pacientes, ambos sexos, 15-45 años, concurrentes a un servicio privado (19 por ciento) y dos públicos (81 por ciento), uno céntrico y otro marginal. Variables investigadas: consumo de lácteos y alimentos dulces, estado bucal y escolaridad. Se aplicaron pruebas estadísticas t de student, ANOVA y chi-cuadrado. Promedios hallados: cariados 1,7 ±2,0 en privado, 4,1±2,8 en públicos (p=0.0001); ausentes 5,4±5,2 en privado, 6,8±5,4 en públicos (p=0.04); obturados 4,4±4,2 en privado, 1,3±2,2 en públicos (p<0.0001). Nivel de escolaridad: superior en el privado (p<0.0001). Consumo diario de lácteos: mayoría en privados (p<0.001). En los servicios públicos los pacientes reemplazan la leche por el mate y relacionan su ingesta con la gravidez, lactancia o la dejan para los niños. Tipos de golosinas o dulces de riesgo consumidos: en el sector privado fueron panificados tipo facturas, tortas, galletitas y dulces, y en los públicos caramelos blandos, alfajores y dulce de leche. El consumo de alimentos dulces de menor riesgo fue de helados, pastillas, gaseosas y chocolates en los privados y de caramelos duros y chicles con y sin azúcar en los públicos. Si bien un alto número de personas los ingieren a cualquier hora, los pacientes privados fueron minoría, mientras que en su consumo sólo después de una comida éstos fueron mayoría.