Influence of vaginal birth on lumbopelvic muscle mechanical properties on urinary incontinence.

OBJECTIVE: To identify differences in the muscle mechanical properties of the pelvic floor (PF) and lumbar paravertebral (LP) muscles between young nulliparous and uni/multiparous women. Secondarily, specific behaviors, depending on the presence or absence or urinary incontinence (UI), were also researched. DESIGN: Case-control study. SETTING: Higher education institution. PARTICIPANTS: One hundred young women participated, divided into two groups depending on whether they had vaginal birth (nulliparous or uni/multiparous). Each group included women with and without UI. MAIN MEASURES: A muscle mechanical properties (tone, stiffness, decrement-inverse of elasticity-, and viscoelastic properties: relaxation and creep) assessment of the PF and LP muscles were performed with a hand-held tonometer. RESULTS: Tone and stiffness of both sides of the PF presented group by UI interaction (p < 0.05), with uni/multiparous women with UI showing higher tone and stiffness compared to multiparous women without UI. In LP muscles, uni/multiparous women showed greater tone and stiffness on the right and left sides [-2.57 Hz (95% confidence interval -4.42,-0.72) and -79.74 N/m (-143.52,-15.97); -2.20 Hz (-3.82,-0.58) and -81.30 N/m (-140.66-,21.95), respectively], as well as a decrease in viscoelastic properties compared to nulliparous women [relaxation: 2.88 ms (0.31,5.44); creep: 0.15 (0.01,0.30); relaxation: 2.69 ms (0.13,5.25); creep: 0.14 (0,0.28), respectively]. CONCLUSIONS: Vaginal birth and UI have a differential influence on the muscle mechanical properties of the PF and LP muscles. The determination of muscle mechanical properties by externally applied hand-held tonometry improves the knowledge of the lumbopelvic status, with applicability in clinical and research fields.

Factors Associated With Mortality in Patients With Immune-Mediated Rheumatic Diseases and COVID-19 From Latin America: Data From Argentina, Mexico, and Brazil.

OBJECTIVE: To describe characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) from Argentina, Mexico and Brazil, and to assess factors associated with mortality in this population. METHODS: Data from 3 national registries, SAR-COVID (Argentina), CMR-COVID (Mexico), and ReumaCoV-Brasil (Brazil), were combined. Adult patients with IMIDs and SARS-CoV-2 infection were recruited. Sociodemographic data, comorbidities, IMID clinical characteristics and treatment, and SARS-CoV-2 infection presentation and outcomes were recorded. RESULTS: A total of 4827 individuals were included: 2542 (52.7%) from SAR-COVID, 1167 (24.2%) from CMR-COVID, and 1118 (23.1%) from ReumaCoV-Brasil. Overall, 82.1% were female with a mean age of 49.7 (SD, 14.3) years; 22.7% of the patients were hospitalized, and 5.3% died because of COVID-19 (coronavirus disease 2019). Argentina and Brazil had both 4% of mortality and Mexico 9.4%. In the multivariable analysis, older age (≥60 years; odds ratio [OR], 7.4; 95% confidence interval [CI], 4.6-12.4), male sex (OR, 1.5; 95% CI, 1.1-2.1), living in Mexico (OR, 3.0; 95% CI, 2.0-4.4), comorbidity count (1 comorbidity: OR, 1.5; 95% CI, 1.0-2.1), diagnosis of connective tissue disease or vasculitis (OR, 1.8; 95% CI, 1.3-2.4), and other diseases (OR, 2.6; 95% CI, 1.6-4.1) compared with inflammatory joint disease, high disease activity (OR, 4.2; 95% CI, 2.5-7.0), and treatment with glucocorticoids (OR, 1.9; 95% CI, 1.4-2.5) or rituximab (OR, 4.2; 95% CI, 2.7-6.6) were associated with mortality. CONCLUSIONS: Mortality in patients with IMIDs was particularly high in Mexicans. Ethnic, environmental, societal factors, and different COVID-19 mitigation measures adopted have probably influenced these results.

Vitamin D and adolescent idiopathic scoliosis, should we stop the hype? A cross-sectional observational prospective study based on a geometric morphometrics approach.

PURPOSE: There is strong evidence supporting the presence of fluctuating asymmetry (FA) in Adolescents with Idiopathic Scoliosis (AIS). Additionally, recent research investigating the relationship between vitamin D and AIS found a relation between them. We hypothesize a negative correlation between FA and vitamin D. METHODS: We performed a surface scan of the torso of 53 AIS patients, a blood test to measure vitamin D and the radiographic Cobb angle. A correlation analysis between vitamin D and FA was carried out to test our hypothesis, and a regression of vitamin D on 3D shape was performed to observe shape differences between the vitamin D deficiency and insufficiency groups. RESULTS: There was no correlation between vitamin D and FA. We found a strong negative correlation between vitamin D and the Cobb angle only in the premenarche group (n = 7; r = - 0.92). Differences in shape were observed between the deficiency and insufficiency groups, and that differences were related to the width of the torso, but not the rotation or lateral flexion. CONCLUSIONS: Our results do not support the massive screening of vitamin D in AIS. Shape analysis revealed differences between the shape of the deficiency and insufficiency groups related to robustness. However, this finding had no relation with the scoliosis characteristics, it just reflected different body composition, and its importance should be explored in future.

Effect of surface treatment and manufacturing process on the shear bond strength of veneering composite resin to polyetherketoneketone (PEKK) and polyetheretherketone (PEEK).

STATEMENT OF PROBLEM: Polyaryletherketones (PAEKs) are high-performance polymer materials in which polyetheretherketone (PEEK) and polyetherketoneketone (PEKK) are the most used. Although mechanical and shear bonding strength tests have been performed on the 2 materials, studies on the influence of processing on bonding are scarce. PURPOSE: The purpose of this in vitro study was to determine the influence of the surface treatment and the manufacturing process on the shear bond strength of veneering composite resin to PEKK and PEEK. MATERIAL AND METHODS: Thirty pressed PEKK, 30 milled PEKK, and 30 milled PEEK specimens were distributed in 6 groups (n=13) as per the manufacturing process and treatment surface. The specimens were either treated with airborne-particle abrasion with 110-µm aluminum oxide, or no surface treatment was applied. Moreover, the PEKK specimens were grouped regarding their manufacturing process, as either milled or heat-pressed. The specimens were all bonded by using a methyl methacrylate-based adhesive (visio.link), and composite resin (Gradia Revolution 2) was bonded to the specimens. An Instron universal machine was used to calculate the shear bond strength between the PEEK or PEKK and the composite resin. Two specimens from each group had their topography modification assessed with a scanning electron microscope. Statistical analysis was performed by using a 3-way ANOVA for multiple comparisons (α=0.05) RESULTS: The groups that were surface treated with 110-µm aluminum oxide (Al2O3) before bonding showed significantly higher shear bond strength (P=.001) than the other groups. However, no statistically significant difference was observed among the groups, regardless of the manufacturing process (milled or heat-pressed) (P=.607). CONCLUSIONS: PEEK and PEKK surfaces treated with 110-µm aluminum oxide airborne-particle abrasion displayed better shear bond strength to composite resin. The manufacturing process (milled or heat-pressed) did not significantly affect the bond strength of PEKK when subjected to the same bonding process.

Optimization of sonication parameters to obtain food emulsions stabilized by zein: formation of zein-diutan gum/zein-guar gum complexes.

BACKGROUND: Zein as a sole material is not suitable for technological applications since it is not flexible. A possible solution to extend the applications of zein is the formation of zein-polysaccharide complexes. As a first step, sonication parameters were optimized to obtain finer emulsions formulated with zein, rosemary essential oil as food preservative, and sunflower oil, by means of response surface methodology. After the formation of these guar- or diutan-zein complexes the rheological properties of these food emulsions were evaluated. RESULTS: An increase in sonication power, sonication time and cycles provoked a decrease in mean droplet size and a lack of recoalescence. The optimized emulsion was the starting point to form two different complexes: zein with diutan gum and zein with guar gum at different concentrations. Rheological properties as well as the microstructure observed by field emission scanning electron microscopy (FESEM) were analyzed. Interestingly, zein-guar gum complexes did not form a rheological gel; as a consequence, emulsions containing them seem to undergo a destabilization process with aging time. In contrast, emulsions formulated with zein-diutan gum presented a 3D network, observed by FESEM technique and proved by rheological measurements. CONCLUSION: While emulsions containing zein-guar gum complexes did not form networks to stabilize oil droplets, zein-diutan gum complexes did. This work brings to light the importance of the selection of polysaccharide used in food emulsions formulated with zein. © 2021 Society of Chemical Industry.

Differences in oral food challenge reaction severity based on increasing age in a pediatric population.

BACKGROUND: Food allergy reactions range from mild to severe with differences in age appearing to be an important factor associated with reaction severity. OBJECTIVE: To define differences in oral food challenge (OFC) reaction severity in pediatric patients from infancy to adolescence using objective clinical outcomes and standardized reaction grading tools. METHODS: Retrospective review of all positive OFC results at 2 large institutions between September 2016 and February 2019. Reaction severity was defined by presence of cardiovascular, neurologic, lower respiratory, or laryngeal symptoms, epinephrine requirement, and grading using 2 established food allergy reaction scales. RESULTS: Infants and toddlers had fewer reactions involving cardiovascular, neurologic, lower respiratory, or laryngeal symptoms compared with older age groups. Epinephrine was also required less frequently during reactions in infants and toddlers, compared with older age groups. There was no difference in reaction severity in infants and toddlers based on clinical history of eczema. Increasing age was significantly correlated with increased epinephrine requirement (R2 = 0.12, P = .002), elevated Consortium of Food Allergy Research score (R2 = .012, P = .003), and approached significance for increased Practical Allergy score (R2 = .005, P = .05). History of asthma and sesame allergy were identified to be positively correlated with more severe reactions. CONCLUSION: Infants and young toddlers have less severe reactions during OFCs compared with older age groups supporting early food introduction practices. In children under 12 months of age, severe reactions are most rare calling into question screening practices using specific allergy testing before food introduction. Standardized reaction grading tools may be valuable instruments to categorize reaction severity during OFCs.

Microencapsulated Bifidobacterium bifidum and Lactobacillus gasseri in Combination with Quercetin Inhibit Colorectal Cancer Development in ApcMin/+ Mice.

Recent studies have suggested that flavonoids such as quercetin and probiotics such as Bifidobacterium bifidum (Bf) and Lactobacillus gasseri (Lg) could play a relevant role in inhibiting colon cancer cell growth. Our study investigated the role of dietary supplementation with microencapsulated probiotics (Bf and Lg) along with quercetin in the development of mouse colorectal cancer (CRC). Methods: Adenomatous polyposis coli/multiple intestinal neoplasia (ApcMin/+) mice were fed a standard diet or the same diet supplemented with microencapsulated probiotics (Bf and Lg strains, 107 CFU/100 g food) or both probiotics strains plus microencapsulated quercetin (15 mg/100 g food) for 73 days. Changes in body and organ weights, energy metabolism, intestinal microbiota, and colon tissue were determined. The expression of genes related to the Wnt pathway was also analyzed in colon samples. Results: Dietary supplementation with microencapsulated probiotics or microencapsulated probiotics plus quercetin reduced body weight loss and intestinal bleeding in ApcMin/+ mice. An improvement in energy expenditure was observed after 8 weeks but not after 10 weeks of treatment. A supplemented diet with microencapsulated Bf and Lg reduced the number of aberrant crypt foci (ACF) and adenomas by 45% and 60%, respectively, whereas the supplementation with Bf, Lg and quercetin decreased the number of ACF and adenomas by 57% and 80%, respectively. Microencapsulated Bf and Lg in combination with quercetin could exert inhibition of the canonical Wnt/ß-catenin signaling pathway in the colon of ApcMin/+ mice Conclusions: The administration of microencapsulated Bf and Lg, individually or in combination with quercetin, inhibits the CRC development in ApcMin/+ mice.

Status of Sleep Apnea and Snoring Disorder Curriculum in U.S. Advanced Education Prosthodontic Programs.

PURPOSE: To assess the management of sleep apnea and snoring disorders in Advanced Education Programs in Prosthodontics (AEPP) in the United States. MATERIALS AND METHODS: A 51 item, online survey was sent to program directors at 48 AEPPs in the United States in 2015. Data results were analyzed descriptively. RESULTS: Thirty-five program directors responded to the survey. Twenty-four (68.6%, N = 35) programs report not having a dedicated course for the treatment of sleep apnea and snoring disorders. The majority (94.3%) of programs chose to treat sleep disordered breathing with oral appliance therapy and 80.0% (N = 35) of programs utilize customized sleep apnea oral devices. However, only 48.6% (N = 35) and 51.4% (N = 35) of programs regularly address sleep apnea and snoring disorders at initial examination during the comprehensive exam and medical history questionnaire, respectively. CONCLUSIONS: The confidence interval for this survey is 8.71 at a confidence level of 95% due to a response rate of 72.9%. This confidence interval suggests there is responder bias in the survey results. Therefore, the results of this survey provide a suggestion of how sleep disorders are managed in AEPPs. Programs appear to be consistent among each other with regards to treatment modalities for sleep disordered breathing. The results suggest that patients are not screened enough to receive treatment addressing sleep disorders.

A fully digital approach to fabricating a CAD-CAM ceramic crown to fit an existing removable partial denture.

The use of a fully digital approach to fabricate an anatomic contour crown to fit an existing removable prosthesis allows the dentist and the dental laboratory technician to work efficiently in a digital environment. This report presents a series of patient treatments involving the fabrication of an anatomic contour monolithic zirconia crown to retrofit an existing removable partial denture. A complete digital workflow comprises an intraoral digital scan and computer-aided design and computer-aided manufacturing (CAD-CAM) technology.

Wear Characteristics and Volume Loss of CAD/CAM Ceramic Materials.

PURPOSE: In the field of prosthodontics, patients often require complex and extensive restorative care. This can involve the use of dental restorations to restore teeth on both the maxillary and mandibular arch. Current literature has evaluated the wear properties of different dental ceramics against enamel, but studies regarding dental ceramics opposing one another are limited. The purpose of this study was to assess the wear potential and wear behavior of CAD/CAM zirconia (ZR) and lithium disilicate (LD) materials against a similar ceramic material, and how the surface finish of these dental ceramics might affect patterns of wear. MATERIALS AND METHODS: Using a sphere-on-plate tribometer system, different surface finishes (glazed-G and glazed then polished-GP) of ZR and LD were evaluated following wear simulation. Artificial saliva of physiologic pH was used as a lubricant during wear simulation at 37°C. The coefficient of friction (COF) was calculated during the wear simulation. After wear simulation was complete, volume loss, surface roughness, and surface characterization of the specimens were analyzed using white-light interferometry and scanning electron microscopy (SEM). Statistical significance between materials and surface finish was established with two-way ANOVA and Bonferroni post hoc test (α = 0.05). RESULTS: Based on the 2-way ANOVA, material (p = 0.002) significantly affected the COF. LD showed a higher COF (p = 0.002) than ZR. Material (p < 0.001) and surface finish (p = 0.004) significantly affected the surface roughness inside the scar. ZR had significantly lower surface roughness compared to LD (p < 0.001). For outside scar, surface finish (p < 0.001) significantly affected the surface roughness. Polished specimens showed significantly higher roughness compared to glazed specimens for both inside (p = 0.004) and outside scar (p < 0.001). For volume loss, material (p < 0.001) and the interaction between material and surface finish (p < 0.001) were statistically significant. LD had higher volume loss than ZR (p < 0.001). For both glazed and polished finished, LD-G and LD-GP had significantly higher volume loss than ZR-G (p = 0.028), and ZR-GP (p < 0.001), respectively. SEM analysis indicated particle build-up and a grooving mechanism of wear for the LD-GP specimens. This suggested a three-body wear phenomenon occurring for LD-GP specimens, which was not visible in SEM imaging for other specimen types. CONCLUSIONS: This study demonstrated the resistance to wear and low abrasiveness of ZR when compared to LD in a simulated masticatory environment. This can be best explained by the increased strength of ZR, and the introduction of three-body wear to LD specimens from the accumulation of embedded wear debris onto its surface. Wear data and comparison of SEM images following wear simulation confirmed this interpretation.

Effect of brushing and thermocycling on the shade and surface roughness of CAD-CAM ceramic restorations.

STATEMENT OF PROBLEM: The effects of toothbrushing (B) and thermocycling (TC) on the surface texture of different materials with various fabrication processes have been investigated. However, studies of computer-aided design and computer-aided manufacturing (CAD-CAM) ceramic restorations are limited. PURPOSE: The purpose of this in vitro study was to evaluate the effect of B and TC on the color stability and surface roughness of extrinsically characterized and glazed CAD-CAM ceramic restorations. MATERIAL AND METHODS: Lithium disilicate CAD ceramic (n=90) and zirconia ceramic (n=90) were studied. All specimens were crystallized/sintered, characterized, and glazed following the manufacturer's recommendation. The specimens were divided into 9 different groups: B, TC, and a combination of B plus TC (B+TC). Brushing was performed at 50 000, 100 000, and 150 000 cycles, simulating an oral environment of 5, 10, and 15 years. Thermocycling was performed at 6000, 12 000, and 18 000 cycles, simulating an oral environment of 5, 10, and 15 years. Brushing plus TC was performed with the combination of the 50 000 cycles of B, then 6000 cycles of TC, and 10 000 cycles of B, then 12 000 cycles of TC, and 15 000 cycles of B, then 18 000 cycles of TC. The color and surface roughness of each specimen were measured before and after all interventions with simulated cycles. Color differences (ΔE) and surface roughness (ΔRa) data were analyzed using 2-way ANOVA, followed by the least significant difference test (α=.05). The correlation between ΔE and ΔRa was statistically analyzed using the Pearson correlation analysis. RESULTS: Within the lithium disilicate CAD groups, intervention did not result in any significant differences in color change (P>.05). Within the zirconia groups, a 15-year clinical simulation revealed significantly higher ΔE values than a simulated 5-year exposure (P=.017). Increased simulated cycles showed significantly higher Ra values for all groups. Within the zirconia groups, B revealed significantly smoother surfaces than TC (P<.001) and B+TC interventions (P<.001). For the zirconia, simulating B+TC for15 years revealed significantly higher Ra values than the groups of B+TC for 5 years (P<.001) and B+TC for 10 years (P=.003). No correlation (lithium disilicate CAD, r=.079; P=.462; zirconia, r=.001; P=.989) was found between the color change and surface roughness. CONCLUSIONS: For both lithium disilicate CAD and zirconia, color changes were below the selected clinical perceptible threshold (ΔE=2.6) after all intervention and simulated cycles. All mean surface roughness measurements were below 0.2 µm. Generally, the surface of both lithium disilicate CAD and zirconia became rougher. No correlation was found between color difference and surface roughness for either material.

Wear and Corrosion Interactions at the Titanium/Zirconia Interface: Dental Implant Application.

PURPOSE: Dental implants have been shown to have predictable success, but esthetic complications often arise. To reduce tissue shadowing from titanium, zirconia abutments may be used; however, the literature suggests that the use of zirconia leads to greater destruction of the implant interface that may result in biological complications such as titanium tattoos and heavy metal toxicity. Previous studies have examined the mechanical aspects of this implant/abutment relationship, but they have not accounted for the corrosive degradation that also takes place in the dynamic environment of the oral cavity. This study investigated the combined effect of both wear and corrosion on the materials at the implant and abutment interface. MATERIALS AND METHODS: Using a simulated oral tribocorrosive environment, titanium (Ti) and zirconia (Zr) abutment materials were slid against titanium and Roxolid implant alloys. The four couplings (Ti/Ti, Ti/Rox, Zr/Ti, Zr/Rox) were selected for the tribocorrosion tests (N = 3). The testing was conducted for 25K cycles, and the coefficient of friction (CoF) and voltage evolution were recorded simultaneously. Following the tribocorrosion assays, the wear volume loss was calculated, and surface characterization was performed. Statistical analysis was completed using a one-way ANOVA followed by post-hoc Bonferroni comparisons. RESULTS: Zr/Ti groups had the highest CoF (1.1647), and Ti/Ti had the lowest (0.5033). The Zr/Ti coupling generated significantly more mechanical damage than the Ti/Ti group (p = 0.021). From the corrosion aspect, the Ti/Ti groups had the highest voltage drop (0.802 V), indicating greater corrosion susceptibility. In comparison, the Zr/Roxolid group had the lowest voltage drop (0.628 V) and significantly less electrochemical degradation (p = 0.019). Overall, the Ti/Ti group had the largest wear volume loss (15.1 × 107 µm3 ), while the Zr/Ti group had the least volume loss (2.26 × 107 µm3 ). Both zirconia couplings had significantly less wear volume than the titanium couplings (p < 0.001). CONCLUSIONS: This study highlights the synergistic interaction between wear and corrosion, which occurs when masticatory forces combine with the salivary environment of the oral cavity. Overall, the zirconia groups outperformed the titanium groups. In fact, the titanium groups generated 5 to 6 times more wear to the implant alloys as compared with the zirconia counterparts. The best performing group was Zr/Ti, and the worst performing group was Ti/Ti.

Quantitative analysis of genomic DNA degradation in whole blood under various storage conditions for molecular diagnostic testing.

Proper storage of whole blood is crucial for isolating nucleic acids from leukocytes and to ensure adequate performance of downstream assays in the molecular diagnostic laboratory. Short-term and long-term storage recommendations are lacking for successful isolation of genomic DNA (gDNA). Container type (EDTA or heparin), temperature (4 °C and room temperature) and time (1-130 days) were assessed as criterion for sample acceptance policies. The percentage of integrated area (%Ti) between 150 and 10,000 bp from the 2200 TapeStation electropherogram was calculated to measure gDNA degradation. Refrigerated EDTA samples yielded gDNA with low %Ti (high quality). Heparinized samples stored at room temperature yielded gDNA of worst quality. Downstream analysis demonstrated that the quality of the gDNA correlated with the quality of the data; samples with high %Ti generated significantly lower levels of high molecular weight amplicons. Recommendations from these analyses include storing blood samples intended for nucleic acid isolation in EDTA tubes at 4 °C for long term storage (>10 days). gDNA should be extracted within 3 days when blood is stored at room temperature regardless of the container. Finally, refrigerated heparinized samples should not be stored longer than 9 days if expecting high quality gDNA isolates. Laboratories should consider many factors, in addition to the results obtained herein, to update their policies for sample acceptance for gDNA extraction intended for molecular genetic testing.

Molecular and cytogenetic evaluation of a patient with ring chromosome 13 and discordant results.

We describe the case of a male newborn with ring chromosome 13 found to have dysmorphic features, growth retardation, imperforate anus, and ambiguous genitalia. An initial karyotype showed 46,XY,r(13)(p13q34) in the 30 cells analyzed. SNP microarray from peripheral blood revealed not only an 8.14-Mb 13q33.2q34 deletion, but also a duplication of 87.49 Mb suggesting partial trisomy 13q that the patient did not appear to have clinically. Further cytogenetic characterization detected 3 distinct cell lines in the repeated peripheral blood sample: 46,XY,r(13)(p13q34)[89]/ 46,XY,r(13;13)(p13q34)[7]/45,XY,-13[5] and 2 in cultured fibroblasts: 46,XY,r(13)(p13q34)[65]/45,XY,-13[35]. Repeated molecular studies on peripheral blood and fibroblasts, however, failed to document the initially seen partial trisomy 13q. We postulate that the presence of duplicated material may be evidence of the high burden of duplicate rings in peripheral blood at any given time, with the high rates of cell death caused by mitotically unstable double rings accounting for the repeated microarray results that failed to detect any duplications. We emphasize the correlation between both cytogenetic and molecular studies with thorough clinical assessment and suggest that given the high sensitivity of newer molecular cytogenetic techniques, careful interpretation of results is critical in the context of ring chromosomes.

Cardiovascular and genitourinary anomalies in patients with duplications within the Williams syndrome critical region: phenotypic expansion and review of the literature.

Williams syndrome results from a microdeletion of approximately 1.5 Mb of chromosome 7q11.23. Several patients have been reported with the reciprocal microduplication in association with a variety of phenotypic features including cognitive impairment and typical facial features, though only a few have had birth defects. We report on three probands with duplications within 7q11.23 of variable sizes; two with cardiovascular involvement including aortic dilation and the other with unilateral renal and gonadal agenesis. We offer a comparison with previously reported cases of duplications of 7q11.23. In light of the present cases, we recommend undertaking echocardiographic and renal ultrasound evaluation of patients with documented 7q11.23 duplications. Further, this cytogenetic abnormality should be part of the differential diagnosis for patients with aortic dilation, as well as those with unilateral renal and gonadal agenesis.

Validation of control of allergic rhinitis and asthma test for children (CARATKids)--a prospective multicenter study.

BACKGROUND: Control of Allergic Rhinitis and Asthma Test for Children (CARATKids) is the first questionnaire that assesses simultaneously allergic rhinitis and asthma control in children. It was recently developed, but redundancy of questions and its psychometric properties were not assessed. This study aimed to (i) establish the final version of the CARATKids questionnaire and (ii) evaluate its reliability, responsiveness, cross-sectional validity, and longitudinal validity. METHODS: A prospective observational study was conducted in 11 Portuguese centers. During two visits separated by 6 wk, CARATKids, visual analog scale scales and childhood asthma control test were completed, and participant's asthma and rhinitis were evaluated by his/her physician without knowing the questionnaires' results. Data-driven item reduction was conducted, and internal consistency, responsiveness analysis, and associations with external measures of disease status were assessed. RESULTS: Of the 113 children included, 101 completed both visits. After item reduction, the final version of the questionnaire has 13 items, eight to be answered by the child and five by the caregiver. Its Cronbach's alpha was 0.80, the Guyatt's responsiveness index was -1.51, and a significant (p < 0.001) within-patient change of CARATKids score in clinical unstable patients was observed. Regarding cross-sectional validity, correlation coefficients of CARATKids with the external measures of control were between 0.45 and -0.69 and met the a priori predictions. In the longitudinal validity assessment, the correlation coefficients between the score changes of CARATKids and those of external measures of control ranged from 0.34 to 0.46. CONCLUSION: CARATKids showed adequate psychometric properties and is ready to be used in clinical practice.

A novel mutation in the SLC40A1 gene associated with reduced iron export in vitro.

Ferroportin disease is an inherited disorder of iron metabolism and is caused by mutations in the ferroportin gene (SLC40A1). We present a patient with hyperferritinemia, iron overload in the liver with reticuloendothelial distribution and also in the spleen, and under treatment with erythropheresis. A molecular study of the genes involved in iron metabolism (HFE, HJV, HAMP, TFR2, SLC40A1) was undertaken. In vitro functional studies of the novel mutation found in the SLC40A1 gene was performed. The patient was heterozygous for a novel mutation, c.386T>C (p.L129P) in the SLC40A1 gene; some of his relatives were also heterozygous for this mutation. In vitro functional studies of the L129P mutation on ferroportin showed it impairs its capacity to export iron from cells but does not alter its sensitivity to hepcidin. These findings and the iron overload phenotype of the patient suggest that the novel mutation c.386T>C (p.L129P) in the SLC40A1 gene has incomplete penetrance and causes the classical form of ferroportin disease.

A Machine Learning Approach for Predicting Caco-2 Cell Permeability in Natural Products from the Biodiversity in Peru.

BACKGROUND: Peru is one of the most biodiverse countries in the world, which is reflected in its wealth of knowledge about medicinal plants. However, there is a lack of information regarding intestinal absorption and the permeability of natural products. The human colon adenocarcinoma cell line (Caco-2) is an in vitro assay used to measure apparent permeability. This study aims to develop a quantitative structure-property relationship (QSPR) model using machine learning algorithms to predict the apparent permeability of the Caco-2 cell in natural products from Peru. METHODS: A dataset of 1817 compounds, including experimental log Papp values and molecular descriptors, was utilized. Six QSPR models were constructed: a multiple linear regression (MLR) model, a partial least squares regression (PLS) model, a support vector machine regression (SVM) model, a random forest (RF) model, a gradient boosting machine (GBM) model, and an SVM-RF-GBM model. RESULTS: An evaluation of the testing set revealed that the MLR and PLS models exhibited an RMSE = 0.47 and R2 = 0.63. In contrast, the SVM, RF, and GBM models showcased an RMSE = 0.39-0.40 and R2 = 0.73-0.74. Notably, the SVM-RF-GBM model demonstrated superior performance, with an RMSE = 0.38 and R2 = 0.76. The model predicted log Papp values for 502 natural products falling within the applicability domain, with 68.9% (n = 346) showing high permeability, suggesting the potential for intestinal absorption. Additionally, we categorized the natural products into six metabolic pathways and assessed their drug-likeness. CONCLUSIONS: Our results provide insights into the potential intestinal absorption of natural products in Peru, thus facilitating drug development and pharmaceutical discovery efforts.