Publications by authors named "Rodrigo Andrade"

139 Publications

Effects of pilates on physical-functional performance, quality of life and mood in older adults: Systematic review and meta-analysis of randomized clinical trials.

J Bodyw Mov Ther 2021 10 12;28:502-512. Epub 2021 Jun 12.

Graduate Program in Aging Sciences from the University Sao Judas Tadeu (USJT), São Paulo, SP, Brazil; Laboratory Study of Movement, Instituto de Ortopedia e Traumatologia Do Hospital Das Clínicas (IOT-HC), Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.

Objective: To systematically review the effects of pilates on physical-functional aspects and quality of life of older adults.

Methods: We included randomized clinical trials whose participants were older adults, whose intervention was pilates exercises and that used a control group for comparison. The primary outcomes were balance, muscle strength, quality of life. Secondary outcomes were mood, autonomy, and flexibility. The searches were performed in the electronic databases Pubmed, Web of Science, LILACS, Cochrane Library and EMBASE, using terms from MeSH: Aged, elderly, Pilates-Based Exercises, Pilates Training, Pilates, Mat Pilates, Equipment-based Pilates, and synonyms, in May 2020. The meta-analysis, when possible, was performed using the mean and standard deviation values of the groups after the intervention period using the random effects model.

Results: The search rendered 1639 studies, of which 28 articles corresponding to 24 ECRs (897 individuals) were included, most of the studies involved a female population. A meta-analysis was performed only in the balance variable, through the Berg Scale (three RCTs), where there were no significant differences between the intervention and control groups (2.06-95% CI: 1.31, 5.44, I: 91%), and it was evaluated by the TUG (six RCTs), which showed a reduction of 0.92 seconds in the protocol execution (95% CI: 1.67, -0.17, I: 62%).

Conclusion: This review demonstrate that the practice of pilates by older adults may have positive effects on some of the outcomes evaluated, these results should be interpreted with caution (methodological heterogeneity and a part present high risk of bias).
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http://dx.doi.org/10.1016/j.jbmt.2021.06.005DOI Listing
October 2021

Aspidosperma and Strychnos alkaloids: Chemistry and biology.

Alkaloids Chem Biol 2021 21;86:1-143. Epub 2021 Sep 21.

Department of Chemistry, Temple University, Philadelphia, PA, United States.

Of Nature's nearly 3000 unique monoterpene indole alkaloids derived from tryptophan, those members belonging to the Aspidosperma and Strychnos families continue to impact the fields of natural products (i.e., isolation, structure determination, biosynthesis) and organic chemistry (i.e., chemical synthesis, methodology development) among others. This review covers the biological activity (Section 2), biosynthesis (Section 3), and synthesis of both classical and novel Aspidosperma (Section 4), Strychnos (Section 5), and selected bis-indole (Section 6) alkaloids. Technological advancements in genetic sequencing and bioinformatics have deepened our understanding of how Nature assembles these intriguing molecules. The proliferation of innovative synthetic strategies and tactics for the synthesis of the alkaloids covered in this review, which include contributions from over fifty research groups from around the world, are a testament to the creative power and technical skills of synthetic organic chemists. To be sure, Nature-the Supreme molecular architect and source of a dazzling array of irresistible chemical logic puzzles-continues to inspire scientists across multiple disciplines and will certainly continue to do so for the foreseeable future.
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http://dx.doi.org/10.1016/bs.alkal.2021.05.001DOI Listing
October 2021

Domino Michael/Mannich Annulation Reaction of -Sulfinyl Lithiodienamines.

Org Lett 2021 09 2;23(18):7014-7017. Epub 2021 Sep 2.

Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122, United States.

The domino Michael/Mannich (DMM) annulation reaction between an -sulfinyl lithiodienamine and an electrophilic alkene is developed for the synthesis of chiral 2-amino cyclohexenes, a key building block in asymmetric synthesis. The DMM reaction proceeds at low temperature while maintaining the stereochemical fidelity. The product functionalized amino cyclohexenes, here obtained in 55-82% yield with diastereomeric ratios as high as >19:1.
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http://dx.doi.org/10.1021/acs.orglett.1c02201DOI Listing
September 2021

Synthesis, Biological Evaluation, and Computational Analysis of Biaryl Side-Chain Analogs of Solithromycin.

ChemMedChem 2021 Nov 3;16(21):3368-3373. Epub 2021 Sep 3.

Department of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA 19122, USA.

There is an urgent need for new antibiotics to mitigate the existential threat posed by antibiotic resistance. Within the ketolide class, solithromycin has emerged as one of the most promising candidates for further development. Crystallographic studies of bacterial ribosomes and ribosomal subunits complexed with solithromycin have shed light on the nature of molecular interactions (π-stacking and H-bonding) between from the biaryl side-chain of the drug and key residues in the 50S ribosomal subunit. We have designed and synthesized a library of solithromycin analogs to study their structure-activity relationships (SAR) in tandem with new computational studies. The biological activity of each analog was evaluated in terms of ribosomal affinity (K determined by fluorescence polarization), as well as minimum inhibitory concentration assays (MICs). Density functional theory (DFT) studies of a simple binding site model identify key H-bonding interactions that modulate the potency of solithromycin analogs.
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http://dx.doi.org/10.1002/cmdc.202100435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571068PMC
November 2021

L5 Radiculopathy After Formal Reduction of High-Grade SDSG Type 5 and 6 L5-S1 Isthmic Spondylolisthesis with 2-Year Follow-Up.

Int J Spine Surg 2021 Aug 19;15(4):645-653. Epub 2021 Jul 19.

Post-Graduate Program in Health Science, Biomechanics and Musculoskeletal Rehabilitation Laboratory, University Santo Amaro, São Paulo, Brazil.

Background: Surgery is the main treatment for patients with high-grade L5-S1 isthmic spondylolisthesis, which can result in neurologic complications, but little is known about its clinical course. The present study evaluated the presence of L5 radiculopathy in high-grade L5-S1 spondylolisthesis in adults in pre- and postoperative periods and after a 2-year follow-up.

Methods: A series of 16 patients who underwent reduction and instrumented fusion for high-grade 5 and 6 spondylolisthesis between 2018 and 2019 were retrospectively evaluated in the pre- and postoperative periods as well as after 6 weeks, 3 months, 6 months, and 1 and 2 years of follow-up. Clinical and surgical data on possible neurological complications of L5 radiculopathy were prospectively collected.

Results: The age was 20.1 ± 12.0 years, and preoperative L5-S1 slip was 89.0%. Five patients presented motor deficit in the preoperative period. In the immediate postoperative period, 9 patients (56%) experienced motor deficits or worsening of the preoperative condition. At the 6-week follow-up, only 1 patient showed resolution of the motor deficit. Three patients presented healed motor deficits after 3 months, and 1 patient demonstrated a healed L5 motor radiculopathy after 6 months. At the 1-year follow-up, only 1 patient exhibited an L5 radiculopathy motor deficit, and at the 2-year follow-up, none of the patients exhibited an L5 radiculopathy motor deficit.

Conclusion: L5 radiculopathy was frequent in the preoperative period and increased after reduction and instrumented fusion of high-grade L5-S1 spondylolisthesis in the postoperative period and in the 6-week follow-up. Three and 6 months after the surgery, there were consecutive motor improvements. After 2 years of follow-up, no patients showed neurological deficit of L5 radiculopathy.

Level Of Evidence: 2.

Clinical Relevance: This is the first study reporting a reduction in complications of L5 neurological motor deficit over a 2-year follow-up in high-grade L5-S1 spondylolisthesis in young adults.
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http://dx.doi.org/10.14444/8085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375700PMC
August 2021

Investigation of phase transition employing strain mapping in TT- and T-NbO obtained by HRTEM micrographs.

Micron 2021 Sep 8;148:103112. Epub 2021 Jul 8.

Nanostructured Materials Lab, Department of Chemistry, Federal University of Minas Gerais, Av. Antônio Carlos, 6627 - 31270-901, Belo Horizonte, Minas Gerais, Brazil.

This work aimed to study the crystalline structure of TT-,T-phases of NbO nanoparticles through XRD, Rietveld refinement, and HRTEM, using geometric phase analysis (GPA). The results show the presence of distorted NbO and NbO polyhedral, producing strain effects, mainly in the plane boundaries and along the b-c plane. XRD and HRTEM analyses show the TT→T transition at 700 °C, with increased particle size and increased strain in the boundaries between nanoparticles. The sample calcinated at 700 °C presents segregation of the TT-(001), (100), and T-(130) planes, where the strain effect is more relevant along the [100] zone axis and between phases.
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http://dx.doi.org/10.1016/j.micron.2021.103112DOI Listing
September 2021

Enamel Renal Syndrome: A Systematic Review.

Indian J Nephrol 2021 Jan-Feb;31(1):1-8. Epub 2021 Jan 27.

Dentistry School, State University of Montes Claros, Unimontes, Minas Gerais State, São Paulo, Brazil.

The enamel renal syndrome (ERS) is a rare autosomal recessive disease that is associated with mutations in the gene. The syndrome is characterized by impaired amelogenesis of the hypoplastic type and nephrocalcinosis, presenting with presence of thin or absence of enamel, late dental eruption, intrapulpal calcifications, bilateral nephrocalcinosis, and normal plasma calcium level. The objective is to characterize ERS by systematically literature reviewing, highlighting the main findings of the syndrome to increase knowledge about this condition in the health professionals. The study is a systematic review of the scientific literature, whose research was developed in the PubMed database in March 2018. A total of 69 articles were found. Two authors analyzed their abstracts and selected, according to the language and main subject, 30 articles to write this study. A total of 69 patients were cited in the studies and their data were analysed. There was gender equivalence and the ages ranged from 1 to 64 years old. There is a clear hereditary relation of the syndrome, since there was consanguinity in 18 cases, indicating a percentage of 26.08% and family history in 30 cases (43.47%). Laboratory changes vary greatly from patient to patient and may even remain unchanged. The relationship between the syndrome and the mutation in the gene can be proven from the data, since all patients with ERS screened by the mutation were positive. With the advancement of the ERS studies, some associations with the syndrome are suspected, such as the presence of gingival fibromatosis, hearing loss, and hypertrichosis. Thus, it is noticed that the syndrome does not show a predilection for gender or age and there is a strong hereditary character, marked by the consanguinity and family history of the patients. The association with the gene is reinforced, since the mutation was identified in all patients analyzed.
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http://dx.doi.org/10.4103/ijn.IJN_27_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101666PMC
January 2021

The effect of direct vertebral rotation on the spine parameters (coronal and sagittal) in adolescent idiopathic scoliosis.

J Back Musculoskelet Rehabil 2021 ;34(5):821-828

Health Science Post-Graduate Department, Medical School, University Santo Amaro, São Paulo, Brazil.

Background: Idiopathic scoliosis is accompanied by postural alterations, instability of gait, and functional disabilities. The objective was to verify radiographic parameters (coronal and sagittal) of adolescents with idiopathic scoliosis (AIS) pre- and post-surgery with direct vertebral rotation (DVR), associated with type 1 osteotomies in all segments (except the most proximal) and type 2 in the periapical vertebrae of the curves.

Methods: A prospective study design was employed in which 41 AIS were evaluated and compared pre- and post-surgery. Scoliosis was confirmed by a spine X-ray exam (Cobb angle). Eight radiographic parameters were measured: Cobb angles (thoracic proximal and distal), segmental kyphosis, total kyphosis, lumbar lordosis, pelvic incidence, sacral slope, and pelvic tilt.

Results: The Cobb angle averaged 51.3∘± 14.9∘. Post-surgery, there were significant reductions for the following spine measurement parameters: Cobb angle thoracic proximal (p= 0.003); Cobb angle thoracic distal (p= 0.001); Cobb angle lumbar (p= 0.001); kyphosis (T5-T12, p= 0.012); and kyphosis (T1-T12, p= 0.002). These reductions showed the effectiveness of surgical correction to reduce Cobb angles and improve thoracic kyphosis. The values obtained for lumbar lordosis, pelvic incidence, sacral slope, and pelvic tilt were not significantly different pre- and post-surgery.

Conclusion: The surgical technique of DVR in AIS proved to be effective in the coronal and sagittal parameters directed at Cobb angles and thoracic kyphosis in order to favor the rehabilitation process.
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http://dx.doi.org/10.3233/BMR-200320DOI Listing
September 2021

Burnout and quality of life among correctional officers in a women's correctional facility.

Rev Bras Med Trab 2021 Feb 11;18(3):312-321. Epub 2021 Feb 11.

Departamento de Fisioterapia, Universidade Federal do Ceará - Fortaleza (CE), Brazil.

Introduction: The correctional officer career is considered a stressful and risky occupation that can affect the mental health of workers due to stress and burnout; this syndrome presents itself with physical, psychological, behavioral, and defensive symptoms, ultimately affecting quality of life.

Objectives: To evaluate the sociodemographic profile, burnout levels, and quality of life of female correctional officers in a women's correctional facility, as well as to verify possible correlations between these variables.

Methods: This is a descriptive cross-sectional study performed in a women's correctional facility located in Aquiraz, in the state of Ceará, through the use of 3 evaluation instruments: the Maslach Burnout Inventory-General Survey, the abbreviated version of the World Health Organization Quality of Life instrument, and a general information questionnaire.

Results: Most of the correctional officers were married or cohabiting, aged between 31 and 40 years old, with complete or partial undergraduate education, and at least 1 child. In the burnout investigation, mean scores were 1.9±1.43, indicating a moderate level of burnout. Regarding quality of life, the environment domain presented the lowest scores (57.34%). We observed a correlation between burnout and quality of life, in which the higher the burnout scores, the lower the quality of life reported by correctional officers.

Conclusions: Our data demonstrate that correctional officers face a risk of developing burnout, thus affecting their quality of life; therefore, preventive health care measures are required for these professionals.
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http://dx.doi.org/10.47626/1679-4435-2020-561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879469PMC
February 2021

Mapping the local dielectric constant of a biological nanostructured system.

Beilstein J Nanotechnol 2021 28;12:139-150. Epub 2021 Jan 28.

Departamento de Física, ICEx, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil.

The aim of this work is to determine the varying dielectric constant of a biological nanostructured system via electrostatic force microscopy (EFM) and to show how this method is useful to study natural photonic crystals. We mapped the dielectric constant of the cross section of the posterior wing of the damselfly with nanometric resolution. We obtained structural information on its constitutive nanolayers and the absolute values of their dielectric constant. By relating the measured profile of the static dielectric constant to the profile of the refractive index in the visible range, combined with optical reflectance measurements and simulation, we were able to describe the origin of the strongly iridescent wing colors of this Amazonian rainforest damselfly. The method we demonstrate here should be useful for the study of other biological nanostructured systems.
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http://dx.doi.org/10.3762/bjnano.12.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849231PMC
January 2021

Staphylococcus aureus resistance to albocycline can be achieved by mutations that alter cellular NAD/PH pools.

Bioorg Med Chem 2021 02 7;32:115995. Epub 2021 Jan 7.

Department of Chemistry, Temple University, Philadelphia, PA 19122, United States. Electronic address:

Small molecule target identification is a critical step in modern antibacterial drug discovery, particularly against multi-drug resistant pathogens. Albocycline (ALB) is a macrolactone natural product with potent activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) whose mechanism of action has been elusive to date. Herein, we report biochemical and genomic studies that reveal ALB does not target bacterial peptidoglycan biosynthesis or the ribosome; rather, it appears to modulate NADPH ratios and upregulate redox sensing in the cell consistent with previous studies at Upjohn. Owing to the complexity inherent in biological pathways, further genomic assays are needed to identify the true molecular target(s) of albocycline.
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http://dx.doi.org/10.1016/j.bmc.2021.115995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891091PMC
February 2021

Age, Sex, Body Mass Index, and Laterality in the Foot Posture of Adolescents: A Cross Sectional Study.

J Manipulative Physiol Ther 2020 09 3;43(7):744-752. Epub 2020 Sep 3.

Department of Physical Therapy, Speech and Occupational Therapy, Musculoskeletal Evaluation Laboratory, Faculty of Medicine, University of São Paulo, University of São Paulo, São Paulo, Brazil. Electronic address:

Objective: To investigate the relationship between the right and left foot posture in terms of body mass index (BMI), sex, and age in adolescents aged 10 to 14.

Methods: A total of 1400 adolescents were included. For assessment, the Foot Posture Index (FPI-6) was used. Each foot was assessed and ranked as supinated, normal, or pronated by the sum of the FPI-6 criteria. Each criterion was scored on a scale of -2 to +2, with negative for supinated and positive for pronated posture. A linear mixed model with repeated measures was used for statistical analysis.

Results: Sex, BMI, and right and left foot are associated with FPI-6. The total score attributed for male sex (β = 0.29, P = .04) and the left foot (β = 0.73, P < .001) was higher (male right foot: mean ± standard deviation [SD], 3.09 ± 2.84, male left foot: 3.76 ± 2.80; female right foot: mean ± SD, 2.28 ± 2.61, female left foot: 3.45 ± 2.66; laterality for left foot: mean ± SD, 3.55 ± 2.71, laterality for right foot: mean ± SD, 2.82 ± 2.7). On the other hand, the correlation coefficient for the BMI was negative (β = -0.08, P = < .001), which means that the higher the BMI the lower the score attributed to the FPI-6.

Conclusions: The FPI-6 is positively related to the male sex and the left foot-that is, the predicted score is higher, so the feet tend to present with a tendency to pronation. Although BMI is associated with FPI-6, it was not possible to establish a relationship between high BMI and pronation of the feet.
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http://dx.doi.org/10.1016/j.jmpt.2018.11.035DOI Listing
September 2020

Synthesis and biological evaluation of semi-synthetic albocycline analogs.

Bioorg Med Chem Lett 2020 11 19;30(21):127509. Epub 2020 Aug 19.

Department of Chemistry, Temple University, Philadelphia, PA 19122, United States. Electronic address:

Albocycline (ALB) is a unique macrolactone natural product with potent, narrow-spectrum activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate (VISA), and vancomycin-resistant S. aureus (VRSA) strains (MIC = 0.5-1.0 μg/mL). Described herein is the synthesis and evaluation of a novel series analogs derived from albocycline by functionalization at three specific sites: the C2-C3 enone, the tertiary carbinol at C4, and the allylic C16 methyl group. Exploration of the structure-activity relationships (SAR) by means of minimum inhibitory concentration assays (MICs) revealed that C4 ester analog 6 was twice as potent as ALB, which represents a class of lead compound that can be further studied to address multi-drug resistant pathogens.
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http://dx.doi.org/10.1016/j.bmcl.2020.127509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577960PMC
November 2020

Synthesis of (-)-Melodinine K: A Case Study of Efficiency in Natural Product Synthesis.

J Nat Prod 2020 08 29;83(8):2425-2433. Epub 2020 Jul 29.

Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122, United States.

Efficiency is a key organizing principle in modern natural product synthesis. Practical criteria include time, cost, and effort expended to synthesize the target, which tracks with step-count and scale. The execution of a natural product synthesis, that is, the sum and identity of each reaction employed therein, falls along a continuum of chemical (abiotic) synthesis on one extreme, followed by the hybrid chemoenzymatic approach, and ultimately biological (biosynthesis) on the other, acknowledging the belongs to Nature. Starting materials also span a continuum of structural complexity approaching the target with constituent elements on one extreme, followed by petroleum-derived and "chiral pool" building blocks, and complex natural products (i.e., semisynthesis) on the other. Herein, we detail our approach toward realizing the first synthesis of (-)-melodinine K, a complex bis-indole alkaloid. The total syntheses of monomers (-)-tabersonine and (-)-16-methoxytabersonine employing our domino Michael/Mannich annulation is described. Isolation of (-)-tabersonine from and strategic biotransformation with tabersonine 16-hydroxylase for site-specific C-H oxidation enabled a scalable route. The Polonovski-Potier reaction was employed in biomimetic fragment coupling. Subsequent manipulations delivered the target. We conclude with a discussion of efficiency in natural products synthesis and how chemical and biological technologies define the synthetic frontier.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00310DOI Listing
August 2020

Dolichocarpols A-F, Unprecedented Macrocyclic Humulene-Type Sesquiterpenoids from .

ACS Omega 2020 Jun 2;5(23):13656-13663. Epub 2020 Jun 2.

Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, João Pessoa, 58051-900 Brazil.

Six sesquiterpenoids with unprecedented macrocyclic humulene-type structures, namely, dolichocarpols A-E (-) with ether-bridged bicyclic rings between C-10 and C-2, C-10 and C-7, C-10 and C-6 (×2), and C-6 and C-3 and dolichocarpol F () cyclized between C-7 and C-2 and with an ether bridge between C-10 and C-3, were isolated from roots. The structures of the compounds were elucidated by NMR, MS, and IR data. Absolute configurations of compounds - and were established on the basis of data from electronic circular dichroism, whereas relative configurations of compounds and were suggested by the NOESY spectrum. In addition, a putative biosynthetic pathway of the compounds is proposed. Furthermore, the cytotoxicity of , , and against HCT-116 (human colorectal carcinoma) and L929 (murine fibroblast) was evaluated.
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http://dx.doi.org/10.1021/acsomega.0c00690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301371PMC
June 2020

Lingual Lymphangioma Ablation With High Power Diode Laser: A Case Report.

J Lasers Med Sci 2020 15;11(2):234-237. Epub 2020 Mar 15.

School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Lymphangioma is a rare vascular anomaly that affects the lymphatic vessels. Its etiology is not yet clear and it usually occurs in the head and neck region. This pathology is commonly diagnosed in childhood and there is no consensus about the most effective treatment of it. We report a case of lymphangioma located on the dorsum of the tongue in a 9-year-old boy, with the clinical appearance of small transparent vesicles similar to "frog-eggs". The diagnosis was defined according to the clinical aspect and ultrasound images. The treatment performed consisted of two sessions of ablation with a high-power diode laser. High-intensity diode laser ablation was a safe and effective tool for the treatment of this lesion in the tongue, which provided the patient with a faster, efficient transoperative period and a more comfortable postoperative period.
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http://dx.doi.org/10.34172/jlms.2020.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118497PMC
March 2020

Papillary intralymphatic angioendothelioma: Dabska tumor.

An Bras Dermatol 2020 Mar - Apr;95(2):214-216. Epub 2020 Feb 12.

Pathological Anatomy Service, Studart & Studart Laboratory, Salvador, BA, Brazil.

Papillary intralymphatic angioendothelioma (Dabska tumor) is a rarely metastasizing lymphatic vascular neoplasm that usually affects children and young adults. The majority of these cases occur in soft tissues of extremities, and to date less than 40 cases have been described. Despite the generally indolent evolution, can be locally invasive with the potential to metastasize. We describe a case of a young woman presenting with a plantar lesion, for 9 months and histological diagnosis of Dabska tumor. This neoplasm should be considered in the differential diagnosis of vascular dermatoses, allowing early diagnosis and treatment. Long-term follow-up should be performed.
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http://dx.doi.org/10.1016/j.abd.2019.03.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175045PMC
May 2020

Total Synthesis of (+)--Condyfoline.

Org Lett 2019 12 18;21(23):9594-9597. Epub 2019 Nov 18.

Department of Chemistry , Temple University , Philadelphia , Pennsylvania 19122 , United States.

Herein, we report the first asymmetric total synthesis of aspidospermatan indole alkaloid (+)--condyfoline () in 15 steps from commercially available 2-methylindole-3-carboxaldehyde. Key steps include (1) our domino Michael/Mannich annulation method of -sulfinyl metallodienamines to set three contiguous stereocenters, (2) LiHMDS-mediated cyclization of an ω-tosyloxy -sulfinamide to prepare the signature indole-fused 2-azabicyclo[3.3.1]nonane framework, and (3) DMTSF-promoted spirocyclization of a dithioacetal intermediate to access the final pyrrolidine ring. Functional group manipulations delivered the targeted alkaloid (+)--condyfoline () in 13 steps and 1.25% overall yield from -sulfinylimine (+)-.
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http://dx.doi.org/10.1021/acs.orglett.9b03762DOI Listing
December 2019

Intake, digestibility, and performance of lambs fed spineless cactus cv. Orelha de Elefante Mexicana.

Asian-Australas J Anim Sci 2020 Aug 23;33(8):1284-1291. Epub 2019 Aug 23.

Animal Science Department, Federal Rural University of Pernambuco, Dom Manoel de Medeiros street, s/n, Dois Irmãos, Recife, Pernambuco, 52171-900, Brazil.

Objective: To evaluate the effects of the carmine cochineal-resistant spineless cactus genotypes cv. Orelha de Elefante Mexicana (Opuntia) and Miúda (Nopalea) on the intake and digestibility of nutrients, ingestive behavior, performance, and ultrasound measurements of growing lambs.

Methods: Thirty-six male (non-castrated) Santa Inês lambs were used, with an average age of 6 months and an initial average weight of 22.0±2.9 kg. They were distributed in a completely randomized design with 3 treatments (Tifton hay, Nopalea and Opuntia) and 12 replications, using initial weight as a covariate. The experimental period was 86 days, with the first 30 days used for the adaptation of the animals to the facilities, diets and management, and the remaining 56 days used for evaluation and data collection.

Results: The intake and apparent digestibility of dry matter (DM), organic matter (OM), crude protein (CP), neutral detergent fiber (NDF), total carbohydrates (TC), non-fibrous carbohydrates (NFC), and total digestible nutrients (TDN) showed a significant difference (p<0.05) as a function of the diets, with the Nopalea treatment (p<0.05) increasing DM intake (g/kg and % body weight [BW]), CP, TDN, and TC digestibility, whereas the Tifton hay diet led to a high (p<0.001) neutral detergent fiber corrected for ash and protein (NDFap) g/d intake, NDFap (BW %) and digestibility of said nutrient. There was no effect of treatments (p>0.05) on feeding time, however, rumination time and total chewing time were higher (p<0.05) for animals fed Tifton hay. The performance of the animals was similar (p>0.05). For the ultrasound measurements, Nopalea promoted an increase in the final loin eye area, compared to Tifton hay.

Conclusion: The use of spineless cactus variety Miúda leads to the greater intake and digestibility of nutrients. The evaluated carmine cochineal-resistant spineless cactus genotypes are alternatives for semi-arid regions as they do not negatively affect the performance of growing lambs.
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http://dx.doi.org/10.5713/ajas.19.0328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322643PMC
August 2020

Reliability in Mandibular Movement Evaluation Using Photogrammetry in Patients With Temporomandibular Disorders.

J Manipulative Physiol Ther 2019 05 29;42(4):267-275. Epub 2019 Jun 29.

Department of Physical Therapy, Speech and Occupational Therapy, School of Medicine, University of São Paulo, São Paulo, Brazil.

Objective: The purpose of this study was to propose a quantitative evaluation for mandibular opening-closing movement asymmetries and to verify the intraexaminer and interexaminer reliability using photogrammetry in individuals with and without myogenic temporomandibular disorders.

Methods: Forty-nine female participants between ages 18 and 40 were enrolled in this study. They were assigned to 2 different groups: a temporomandibular disorder group, (n = 25; 28.1 ± 3.6 years) and an asymptomatic group (n = 24; 25.6 ± 5.1 years). Data were collected through photogrammetry using Corel Draw X3 software (Corel Corp, Ottawa, Ontario, Canada) for angle measurements. Reliability analysis was done on the total sample, and the photographs were obtained by a singular examiner on 2 occasions (intraexaminer) 1 month apart and from measurement made by another examiner (interexaminer) on different days. The intraclass correlation coefficient (ICC) was applied with a significance level of 5%.

Results: The photogrammetry had excellent intrarater and inter-rater reliability for the evaluation of opening and closing movements of the jaw (intrarater: opening ICC = 0.99; closing ICC = 0.98; inter-rater: opening ICC = 0.89 and closing ICC = 0.82). Photogrammetry also demonstrated excellent intra- and inter-rater reliability in the evaluation of head posture (intra-rater: head deviation ICC = 0.96; head position ICC = 0.75; inter-rater: head deviation ICC = 0.98; head position ICC = 0.98).

Conclusion: Under these experimental conditions, most angular values presented excellent intra- and interexaminer reliability.
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http://dx.doi.org/10.1016/j.jmpt.2018.11.008DOI Listing
May 2019

Synthesis and biological evaluation of solithromycin analogs against multidrug resistant pathogens.

Bioorg Med Chem Lett 2019 06 26;29(11):1386-1389. Epub 2019 Mar 26.

Department of Chemistry, Temple University, Philadelphia, PA 19122, United States. Electronic address:

Novel antibacterial drugs that treat multidrug resistant pathogens are in high demand. We have synthesized analogs of solithromycin using Cu(I)-mediated click chemistry. Evaluation of the analogs using Minimum Inhibitory Concentration (MIC) assays against resistant Staphylococcus aureus, Escherichia coli, and multidrug resistant pathogens Enterococcus faecium and Acinetobacter baumannii showed they possess potencies similar to those of solithromycin, thus demonstrating their potential as future therapeutics to combat the existential threat of multidrug resistant pathogens.
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http://dx.doi.org/10.1016/j.bmcl.2019.03.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487207PMC
June 2019

Growth and excitability at synapsin II deficient hippocampal neurons.

Mol Cell Neurosci 2019 04 9;96:25-34. Epub 2019 Mar 9.

Department of Neurology, Wayne State University School of Medicine, Detroit, MI, United States of America. Electronic address:

Synapsins are neuronal phosphoproteins that fine-tune synaptic transmission and suppress seizure activity. Synapsin II (SynII) deletion produces epileptic seizures and overexcitability in neuronal networks. Early studies in primary neuronal cultures have shown that SynII deletion results in a delay in synapse formation. More recent studies at hippocampal slices have revealed increased spontaneous activity in SynII knockout (SynII(-)) mice. To reconcile these observations, we systematically re-examined synaptic transmission, synapse formation, and neurite growth in primary hippocampal neuronal cultures. We find that spontaneous glutamatergic synaptic activity was suppressed in SynII(-) neurons during the initial developmental epoch (7 days in vitro, DIV) but was enhanced at later times (12 and18 DIV). The density of synapses, transmission between connected pairs of neurons, and the number of docked synaptic vesicles were not affected by SynII deletion. However, we found that neurite outgrowth in SynII(-) neurons was suppressed during the initial developmental epoch (7 DIV) but enhanced at subsequent developmental stages (12 and18 DIV). This finding can account for the observed effect of SynII deletion on synaptic activity. To test whether the observed phenotype resulted directly from the deletion of SynII we expressed SynII in SynII(-) cultures using an adeno-associated virus (AAV). Expression of SynII at 2 DIV rescued the SynII deletion-dependent alterations in both synaptic activity and neuronal growth. To test whether the increased neurite outgrowth in SynII(-) observed at DIV 12 and18 represents an overcompensation for the initial developmental delay or results directly from SynII deletion we performed "late expression" experiments, transfecting SynII(-) cultures with AAV at 7 DIV. The late SynII expression suppressed neurite outgrowth at 12 and 18 DIV to the levels observed in control neurons, suggesting that these phenotypes directly depend on SynII. These results reveal a novel developmentally regulated role for SynII function in the control of neurite growth.
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http://dx.doi.org/10.1016/j.mcn.2019.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720125PMC
April 2019

Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space.

ACS Cent Sci 2018 Dec 5;4(12):1727-1741. Epub 2018 Dec 5.

Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, Indiana 47405, United States.

Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in collaboration with academic and industry researchers, for quantitative high-throughput screening (qHTS) across a diverse set of cell-based and biochemical assays. Characterization of the library in terms of physicochemical properties, structural diversity, and similarity to compounds in publicly available libraries indicates that the Canvass library contains many structural elements in common with approved drugs. The assay data generated were analyzed using a variety of quality control metrics, and the resultant assay profiles were explored using statistical methods, such as clustering and compound promiscuity analyses. Individual compounds were then sorted by structural class and activity profiles. Differential behavior based on these classifications, as well as noteworthy activities, are outlined herein. One such highlight is the activity of (-)-2()-cathafoline, which was found to stabilize calcium levels in the endoplasmic reticulum. The workflow described here illustrates a pilot effort to broadly survey the biological potential of natural products by utilizing the power of automation and high-throughput screening.
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http://dx.doi.org/10.1021/acscentsci.8b00747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311695PMC
December 2018

Association between Hand Digit Ratio (2D : 4D) and Acute Lymphoblastic Leukemia.

Dis Markers 2018 26;2018:4938725. Epub 2018 Nov 26.

Health Science Program, State University of Montes Claros, Montes Claros, Minas Gerais, Brazil.

Objective: Digit ratio (2D : 4D) has been suggested as a biomarker for prenatal hormone activity and has been linked to several types of cancer. This study investigated the possible correlation between 2D : 4D ratios and acute lymphoblastic leukemia.

Methods: A case-control study was performed with Brazilian subjects. Direct measurements of the lengths of index and ring fingers of both hands of patients with acute lymphoblastic leukemia ( = 43) and controls matched by age and gender ( = 86) were obtained by using a digital vernier caliper. Mean ratios between the second and fourth digits were compared. Data were analyzed by Student's -test with a significance level of 5%.

Results: No significant difference was found between the mean digit ratios of the right and left hands between the groups for any analysis ( > 0.05), neither for the whole sample nor for the distribution by gender.

Conclusions: We observed that patients with acute lymphoblastic leukemia do not have a different digit pattern when compared with unaffected individuals, which may suggest that exposure to prenatal sex hormone is similar between groups.
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http://dx.doi.org/10.1155/2018/4938725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287137PMC
April 2019

Scientific production of the Brazilian Council for Scientific and Technological Development (CNPq) researchers in the field of Oral Medicine and Oral Pathology granted with a scientific productivity fellowship.

Oral Surg Oral Med Oral Pathol Oral Radiol 2018 12 18;126(6):553-554. Epub 2018 Aug 18.

Department of Oral Diagnosis, Dental School, State University of Montes Claros, Montes Claros, Minas Gerais, Brazil; Center for Rehabilitation of Craniofacial Anomalies, Dental School, University of José Rosario Vellano, Alfenas, Minas Gerais, Brazil.

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http://dx.doi.org/10.1016/j.oooo.2018.07.057DOI Listing
December 2018

Ribosome-Templated Azide-Alkyne Cycloadditions Using Resistant Bacteria as Reaction Vessels: Click Chemistry.

ACS Med Chem Lett 2018 Sep 13;9(9):907-911. Epub 2018 Aug 13.

Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122, United States.

click chemistry has been a powerful method for fragment-based drug design since its discovery in 2002. Recently, we demonstrated that the bacterial ribosome can template the azide-alkyne cycloaddition reaction to expedite the discovery of novel antibiotics. We now report this process can be performed in an antibiotic-resistant bacterial cell. The corresponding triazole products formed are potent antibiotics that inhibit bacterial growth; moreover, the potency of each cycloadduct can be visualized using the traditional MIC assay in a 96-well plate format. We characterized the clicked products by independent chemical synthesis and LC-MS analysis, which showed that mass count percent increase was directly proportional to 1/MIC. In other words, potent compounds detected by MIC were formed in greater amounts. Control experiments unambiguously showed the ribosome was responsible for templating triazole formation. Significantly, our method (1) obviates the need to isolate bacterial ribosomes; (2) could be applied to different bacterial strains, which broadens the scope and facilitates the discovery of narrow-spectrum antibiotics; and (3) does not require the knowledge of mode-of-action and thus could uncover novel antibiotic targets. We believe this method could be expanded and implemented as a novel approach for antibiotic drug discovery.
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http://dx.doi.org/10.1021/acsmedchemlett.8b00248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142060PMC
September 2018

Two Tabersonine 6,7-Epoxidases Initiate Lochnericine-Derived Alkaloid Biosynthesis in .

Plant Physiol 2018 08 22;177(4):1473-1486. Epub 2018 Jun 22.

Université de Tours, EA2106 Biomolécules et Biotechnologies Végétales, Tours, F-37200, France

Lochnericine is a major monoterpene indole alkaloid (MIA) in the roots of Madagascar periwinkle (). Lochnericine is derived from the stereoselective C6,C7-epoxidation of tabersonine and can be metabolized further to generate other complex MIAs. While the enzymes responsible for its downstream modifications have been characterized, those involved in lochnericine biosynthesis remain unknown. By combining gene correlation studies, functional assays, and transient gene inactivation, we identified two highly conserved P450s that efficiently catalyze the epoxidation of tabersonine: tabersonine 6,7-epoxidase isoforms 1 and 2 (TEX1 and TEX2). Both proteins are quite divergent from the previously characterized tabersonine 2,3-epoxidase and are more closely related to tabersonine 16-hydroxylase, involved in vindoline biosynthesis in leaves. Biochemical characterization of TEX1/2 revealed their strict substrate specificity for tabersonine and their inability to epoxidize 19-hydroxytabersonine, indicating that they catalyze the first step in the pathway leading to hörhammericine production. and displayed complementary expression profiles, with expressed mainly in roots and in aerial organs. Our results suggest that and originated from a gene duplication event and later acquired divergent, organ-specific regulatory elements for lochnericine biosynthesis throughout the plant, as supported by the presence of lochnericine in flowers. Finally, through the sequential expression of and up to four other MIA biosynthetic genes in yeast, we reconstituted the 19-acetylhörhammericine biosynthetic pathway and produced tailor-made MIAs by mixing enzymatic modules that are naturally spatially separated in the plant. These results lay the groundwork for the metabolic engineering of tabersonine/lochnericine derivatives of pharmaceutical interest.
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http://dx.doi.org/10.1104/pp.18.00549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084683PMC
August 2018

In vivo Antimalarial and Antitrypanosomal Activity of Strychnogucine B, a Bisindole Alkaloid from Strychnos icaja.

Planta Med 2018 Aug 21;84(12-13):881-885. Epub 2018 Jun 21.

Laboratory of Pharmacognosy, CIRM, Université de Liège, Liège, Belgium.

Strychnogucine B is a bisindole alkaloid previously isolated from that possesses promising antiplasmodial properties. This compound was synthesized in four steps from (-)-strychnine. As no acute toxicity was observed at the highest tested cumulative dose of 60 mg/kg, its antimalarial activity was determined intraperitoneally at 30 mg/kg/d in a murine model. In the Peters's 4-d suppressive test, this alkaloid suppressed the parasitaemia by almost 36% on day 5 and 60% on day 7 compared to vehicle-treated mice. In addition to this interesting antimalarial activity, it showed moderate antitrypanosomal activity but no activity in an acute model. It was also inactive on promastigotes. This highlights its selective antimalarial efficacy and leads to further investigation to assess its potential as new antimalarial lead compound.
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http://dx.doi.org/10.1055/a-0644-2723DOI Listing
August 2018

Prevalence of Adolescent Idiopathic Scoliosis in the State of São Paulo, Brazil.

Spine (Phila Pa 1976) 2018 Dec;43(24):1710-1718

Department of Physical Therapy, Speech, and Occupational Therapy, School of Medicine University of São Paulo, São Paulo, Brazil.

Study Design: A cross-sectional study.

Objective: To estimate the prevalence of adolescent idiopathic scoliosis (AIS) in cities in the state of São Paulo, Brazil, as well as to identify demographic, clinical, and lifestyle factors associated with AIS.

Summary Of Background Data: AIS is a common three-dimensional spinal deformity. Epidemiological data about the condition in the southern hemisphere are scarce, and Brazil has no public health policies to implement school-based scoliosis screening programs.

Methods: We assessed 2562 adolescents between 10 and 14 years of age. The screening procedure included measurement of the angle of trunk rotation using a scoliometer in the Adams forward bend test and the radiographic examination.

Results: The overall prevalence of AIS was 1.5% (95% confidence interval [CI]: 1%-1.9%). The AIS prevalence was higher among the females than among the males-2.2% (95% CI: 1.4%-2.9%) and 0.5% (95% CI: 0.1%-0.9%), respectively. The following factors were associated with the development of AIS: being female (OR = 4.7, 95% CI: 1.8-12.2; P = 0.001) and being in the 13- to 14-year age group (OR = 2.2; 95% CI: 1.0-4.8; P = 0.035). Double curves and right laterality were more common (59.4% and 56.8%, respectively), although the curves were of low magnitude (75% of the curves having a Cobb angle ≤22°), as was the progression factor (≤1.2 in 75% of the cases).

Conclusion: The prevalence of AIS in cities within the state of São Paulo was similar to that reported in the literature, was higher among females, and was higher during puberty (13-14 years of age). Because puberty occurs later for males than for females, the recommendation to screen both sexes at 10 to 14 years of age should be reconsidered.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000002725DOI Listing
December 2018
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