Programmed cell senescence during mammalian embryonic development.

Cellular senescence disables proliferation in damaged cells, and it is relevant for cancer and aging. Here, we show that senescence occurs during mammalian embryonic development at multiple locations, including the mesonephros and the endolymphatic sac of the inner ear, which we have analyzed in detail. Mechanistically, senescence in both structures is strictly dependent on p21, but independent of DNA damage, p53, or other cell-cycle inhibitors, and it is regulated by the TGF-ß/SMAD and PI3K/FOXO pathways. Developmentally programmed senescence is followed by macrophage infiltration, clearance of senescent cells, and tissue remodeling. Loss of senescence due to the absence of p21 is partially compensated by apoptosis but still results in detectable developmental abnormalities. Importantly, the mesonephros and endolymphatic sac of human embryos also show evidence of senescence. We conclude that the role of developmentally programmed senescence is to promote tissue remodeling and propose that this is the evolutionary origin of damage-induced senescence.

A murine model for the del(GJB6-D13S1830) deletion recapitulating the phenotype of human DFNB1 hearing impairment: generation and functional and histopathological study.

Inherited hearing impairment is a remarkably heterogeneous monogenic condition, involving hundreds of genes, most of them with very small (< 1%) epidemiological contributions. The exception is GJB2, the gene encoding connexin-26 and underlying DFNB1, which is the most frequent type of autosomal recessive non-syndromic hearing impairment (ARNSHI) in most populations (up to 40% of ARNSHI cases). DFNB1 is caused by different types of pathogenic variants in GJB2, but also by large deletions that keep the gene intact but remove an upstream regulatory element that is essential for its expression. Such large deletions, found in most populations, behave as complete loss-of-function variants, usually associated with a profound hearing impairment. By using CRISPR-Cas9 genetic edition, we have generated a murine model (Dfnb1em274) that reproduces the most frequent of those deletions, del(GJB6-D13S1830). Dfnb1em274 homozygous mice are viable, bypassing the embryonic lethality of the Gjb2 knockout, and present a phenotype of profound hearing loss (> 90 dB SPL) that correlates with specific structural abnormalities in the cochlea. We show that Gjb2 expression is nearly abolished and its protein product, Cx26, is nearly absent all throughout the cochlea, unlike previous conditional knockouts in which Gjb2 ablation was not obtained in all cell types. The Dfnb1em274 model recapitulates the clinical presentation of patients harbouring the del(GJB6-D13S1830) variant and thus it is a valuable tool to study the pathological mechanisms of DFNB1 and to assay therapies for this most frequent type of human ARNSHI.

Theoretical Study of Cyanidin-Resveratrol Copigmentation by the Functional Density Theory.

Anthocyanins are colored water-soluble plant pigments. Upon consumption, anthocyanins are quickly absorbed and can penetrate the blood-brain barrier (BBB). Research based on population studies suggests that including anthocyanin-rich sources in the diet lowers the risk of neurodegenerative diseases. The copigmentation caused by copigments is considered an effective way to stabilize anthocyanins against adverse environmental conditions. This is attributed to the covalent and noncovalent interactions between colored forms of anthocyanins (flavylium ions and quinoidal bases) and colorless or pale-yellow organic molecules (copigments). The present work carried out a theoretical study of the copigmentation process between cyanidin and resveratrol (CINRES). We used three levels of density functional theory: M06-2x/6-31g+(d,p) (d3bj); ωB97X-D/6-31+(d,p); APFD/6-31+(d,p), implemented in the Gaussian16W package. In a vacuum, the CINRES was found at a copigmentation distance of 3.54 Å between cyanidin and resveratrol. In water, a binding free energy ∆G was calculated, rendering -3.31, -1.68, and -6.91 kcal/mol, at M06-2x/6-31g+(d,p) (d3bj), ωB97X-D/6-31+(d,p), and APFD/6-31+(d,p) levels of theory, respectively. A time-dependent density functional theory (TD-DFT) was used to calculate the UV spectra of the complexes and then compared to its parent molecules, resulting in a lower energy gap at forming complexes. Excited states' properties were analyzed with the ωB97X-D functional. Finally, Shannon aromaticity indices were calculated and isosurfaces of non-covalent interactions were evaluated.

Critical shoulder angle and failure of conservative treatment in patients with atraumatic full thickness rotator cuff tears.

BACKGROUND: Atraumatic full thickness rotator cuff tears (AFTRCT) are common lesions whose incidence increases with age. Physical therapy is an effective conservative treatment in these patients with a reported success rate near 85% within 12 weeks of treatment. The critical shoulder angle (CSA) is a radiographic metric that relates the glenoid inclination with the lateral extension of the acromion in the coronal plane. A larger CSA has been associated with higher incidence of AFTRCT and a higher re-tear rate after surgical treatment. However, no study has yet described an association between a larger CSA and failure of conservatory treatment in ARCT. The main objective of this study is to determine whether there is an association between CSA and failure of physical therapy in patients with AFTRCT. METHODS: We reviewed the imaging and clinical records of 48 patients (53 shoulders), 60% female, with a mean age of 63.2 years (95% CI ± 10.4 years); treated for AFTRCT who also underwent a true anteroposterior radiograph of the shoulder within a year of diagnosis of the tear. We recorded demographic (age, sex, type of work), clinical (comorbidities), and imaging data (CSA, size and location of the tear). We divided the patients into two groups according to success or failure of conservative treatment (indication for surgery), so 21 shoulders (39.6%) required surgery and were classified as failure of conservative treatment. Univariate and multivariate analysis was performed to detect predictors of failure of conservative treatment. RESULTS: The median CSA was 35.5º with no differences between those with failure (median 35.5º, range 29º to 48.2º) and success of conservative treatment (median 35.45º, range 30.2º to 40.3º), p = 0.978. The multivariate analysis showed a younger age in patients with failure of conservative treatment (56.14 ± 9.2 vs 67.8 ± 8.4, p < 0.001) and that male gender was also associated with failure of conservative treatment (57% of men required surgery vs 28% of women, p = 0.035). CONCLUSIONS: It is still unclear if CSA does predict failure of conservative treatment. A lower age and male gender both could predicted failure of conservative treatment in AFTRCT. Further research is needed to better address this subject.

Glenoid neck length in a healthy population and its association with scapular notching.

BACKGROUND: Scapular notching is a radiographic finding associated with the use of a reverse shoulder prosthesis. The morphological characteristics of the glenoid neck have been scarcely explored as a relevant factor in relation to scapular notching. The objective of this study is to measure the length of the glenoid neck in a three-dimensional CT reconstruction of a healthy population and to simulate the scapular notching free range of motion for the "long neck" and for the "short neck" groups. METHODS: CT scans of 214 shoulders were reviewed, excluding incomplete, poor quality, or altered studies. 100 CT scans were finally processed. The mean age was 51.7 years (SD 19.4; range, 15-84 years), with 49 female and 51 male patients. For each of the scapulae, four morphometric measurements were obtained: anterior glenoid neck (AGN), middle glenoid neck (MGN), posterior glenoid neck (PGN) and alternative posterior glenoid neck (aPGN). Using 3D software, we simulated a reverse shoulder prosthesis, and the scapular notching free range of motion was registered. Differences between measurements were evaluated with an unpaired t-test using StataIC16®. P-values < 0.05 were considered significant. The intraobserver and interobserver correlation was evaluated with the intraclass correlation coefficient. RESULTS: The AGN measured 7.43 ± 2.52 mm (range, 1.72-13.3 mm); MGN measured 8.05 mm ± 1.93 (range, 2.92-13.2 mm); PGN measured 7.26 ± 2.6 mm (range, 2-13.4 mm); and aPGN measured 8.97 ± 2.3 mm (range, 4.08-15.4 mm). The scapular notching free range of motion for the "long neck" group was 74.98° ± 7.35 (range, 55-83°) and for the "short neck" group, it was 62.93° ± 6.84 (range, 45-70°) (p = 0.0004). CONCLUSIONS: Measurement of posterior glenoid neck length exhibits excellent reliability and reproducibility, as well as being associated to the scapular notching free range of motion. STUDY DESIGN: Basic, retrospective, CT images research.

Increasing incidence of rotator cuff surgery: A nationwide registry study in Chile.

BACKGROUND: The rotator cuff surgery (RCS) incidence is rising rapidly in North America, Europe, Asia, and Australia. Despite this, multiple factors limit patients' access to surgery. In Latin America, barriers to orthopedic surgery have been largely ignored. The purpose of this study was to calculate the rate of RCS in Chile between 2008 and 2018, investigating possible associated factors to access such as age, sex, and the health insurance. METHODS: An ecological study was carried out with nationwide data obtained from the Database of Hospital Discharges of the Department of Statistics. All Chilean inhabitants aged 25 years or more were included. We used the ICD-10 codes M751, M754, and S460. The annual incidence rate of surgeries and the incidence rate for the period studied per 100,000 inhabitants were calculated. Data were analyzed stratified by age, sex, year of study, and the health insurance. Negative binomial regression was used to compare rates. Statistical analyzes were performed with Stata v.14 software. RESULTS: 39,366 RCSs were performed, with a total rate for the period of 32.36 per 100,000 inhabitants. The annual rate of surgeries from 2008 to 2018 increased from 24.55 to 49.11 per 100,000/year. When adjusting for year, an annual increase in surgery rates of 8.19% (95% CI 6.7-9.6) and 101% growth between 2008 and 2018 (95% CI 90-109%, p < 0.001) was observed. When comparing the global rates according to the health insurance, the public system corresponds to 21.3 per 100,000 and the private system to 72 per 100,000, the latter being 3.4-times higher (95% CI 2.7-4.4; p < 0.001). CONCLUSION: RCS rates are increasing in Chile concordantly with previous reports of other western countries. The most important factor associated with RCS rate found was the patients' health insurance, with higher rates observed for the private sector.

[Effectiveness of a self-administered rehabilitation program for shoulder pain syndrome in primary health care]. / Efectividad de un programa de rehabilitación autoadministrado en el tratamiento del síndrome de hombro doloroso en atención primaria de salud: un estudio clínico aleatorizado, simple ciego.

BACKGROUND: Shoulder pain syndrome (SPS) is frequent and management in primary care is precarious, with a high rate of referral without adequate treatment, overloading rehabilitation and orthopedic services. AIM: To assess the effectiveness of a self-administered rehabilitation program in adults with shoulder pain syndrome in primary care. PATIENTS AND METHODS: A randomized, single-blind clinical trial (evaluators) with an experimental group (self-administered rehabilitation) and a control group (standard physical therapy) was carried out in 271 adult patients aged 18 or older with unilateral shoulder pain lasting more than six weeks and less than three months. The primary outcome was the recovery perceived by the patient. Constant score for function, quality of life using SF-36, simple shoulder test (SST) and the Disabilities of the Arm, Shoulder, and Hand (DASH) score were also calculated at six, 12 and 24 weeks of follow-up. RESULTS: The self-administered rehabilitation program showed an adjusted effectiveness of 51% at the end of treatment compared to 54% of the standard physical therapy (p > 0.05). No differences in the evolution of the other scores assessed were observed between groups. CONCLUSIONS: A self-administered rehabilitation program for painful shoulder was non-inferior than usual physical therapy.

Differential organ phenotypes after postnatal Igf1r gene conditional deletion induced by tamoxifen in UBC-CreERT2; Igf1r fl/fl double transgenic mice.

Insulin-like growth factor type 1 receptor (IGF1R) is a ubiquitously expressed tyrosine kinase that regulates cell proliferation, differentiation and survival. It controls body growth and organ homeostasis, but with specific functions depending on developmental time and cell type. Human deficiency in IGF1R is involved in growth failure, microcephaly, mental retardation and deafness, and its overactivation is implicated in oncogenesis. Igf1r-deficient mice die at birth due to growth retardation and respiratory failure. Although multiple Igf1r tissue-specific mutant lines have been analyzed postnatally, using Igf1r-floxed (Igf1r (fl/fl) ) mice mated with diverse cell-type recombinase Cre-expressing transgenics, no mouse models for the study of generalized Igf1r deficiency in adults have been reported. To this end we generated UBC-CreERT2; Igf1r (fl/fl) transgenic mice with an inducible deletion of Igf1r activated by tamoxifen. Tamoxifen administration to 4 week-old prepuberal male mice delayed their growth, producing a distinct impact on organ size 4 weeks later. Whereas testes were smaller, spleen and heart showed an increased organ to body weight ratio. Mosaic Igf1r genomic deletions caused a significant reduction in Igf1r mRNA in all organs analyzed, resulting in diverse phenotypes. While kidneys, spleen and cochlea had unaltered gross morphology, testes revealed halted spermatogenesis, and liver and alveolar lung parenchyma showed increased cell proliferation rates without affecting apoptosis. We demonstrate that UBC-CreERT2 transgenic mice efficiently delete Igf1r upon postnatal tamoxifen treatment in multiple mouse organs, and corroborate that IGF1R function is highly dependent on cell, tissue and organ type.

[Community associated-methicillin-resistant Staphylococcus aureus (SAMR-AC): comunication of the first four pediatric cases in the Roberto del Rio Children's Hospital]. / Staphylococcus aureus resistente a meticilina asociado a la comunidad (SARM-AC): comunicación de los primeros cuatro casos pediátricos descritos en Hospital de Niños Roberto del Río.

Staphylococcus aureus is a known pathogen in pediatric patients that produces skin infections, cutaneous abscess, cellulitis and osteoarticular infections. Most of these infections are produced by a meticilin susceptible strain. The community associated methicillin resistant Staphylococcus aureus was published for the first time in 1993, ever since then is has been recognized as a cosmopolite pathogen. The first report in Latin America was published in 2003, and in Chile in 2008 from adult patients that have reported traveling to other countries. The following series describes four pediatric cases, all school-aged children, diagnosed since 2012 with clinical followups and molecular studies. Two cases presented as osteomyelitis of the lower extremity; and one presented as arm cellulitis. These three cases had Panton Valentine leukocidine (PV-L) negative strains from the clone complex 8. The last case presented a renal abscess, the strain was PV-L positive from the clone complex 30. This case series constitutes the first pediatric case report in Chile.

[The molecular basis of infections associated to orthopedic implants]. / Bases moleculares de la infección asociada a implantes ortopédicos.

Infections associated with the use of orthopedic implants are still the major complication associated with these devices and an unsolved challenge. The frequency of infection associated with orthopedic implant is relatively low, estimated to range between 0.5 to 5%. However, it has devastating consequences for the patient and health institutions. The majority of infections is secondary to gram-positive aerobic microorganisms belonging to the genus Staphylococcus. These bacteria establish chronic infections due to its ability of adhesion and biofilm formation. Biofilms are complex communities in a polysaccharide matrix. This structure retains nutrients and protects the bacteria against the immune response and antimicrobial agents. The study of molecular characteristics and biofilm formation regulation is vital for the understanding of judicious clinical management and the development of novel strategies for the prevention of infection.

Treatment of distal third humeral shaft fractures with posterior minimally invasive plate osteosynthesis (MIPO) with segmental isolation of the radial nerve: minimum one-year follow-up.

Background: Open reduction and internal fixation with plate is one of the most widely used treatments for distal third humeral shaft fractures. The purpose of this study was to report the outcomes of the treatment of distal third humeral shaft fractures with posterior minimally invasive plate osteosynthesis (MIPO) with segmental isolation of the radial nerve. Methods: We performed an observational, retrospective, consecutive, monocentric, continuous multioperator study. We reviewed 22 distal third humeral shaft fractures treated with posterior MIPO in our institution with an extra-articular distal humerus plate from 2018 to 2021. Inclusion was limited to functionally independent patients with displaced fractures involving the junction of the middle and distal thirds of the humerus and minimum 12-month follow-up for implant removal. We assessed clinical outcomes including range of motion; QuickDASH score; Mayo Elbow Performance Score; and Constant-Murley score. Results: The average follow-up period of the sample was 31.7 ± 11.6 months (range, 15.7-51.3 months). The average elbow flexion and extension were 146.4° ± 7.3° (range, 120°-150°) and -0.7° ± 3.3° (range, -15° to 0°), respectively. The average shoulder anterior flexion, elevation, and abduction were 178.6° ± 3.6° (range, 170°-180°), 179.1° ± 2.9° (range, 170°-180°), and 140.9° ± 14.8° (range, 110°-160°), respectively. The average external rotation was 88.6° ± 6.4 (range, 65°-90°). The mean visual analog scale score for pain was 1.0 ± 1.6 (range, 0-5) and the mean Mayo Elbow Performance Score was 90.5 ± 9.9 (range, 70-100). The mean QuickDASH and Constant-Murley scores were 4.7 ± 6.8 (range, 0-20.5) and 95.5 ± 5.1 (range, 81-100), respectively. Two patients presented with relevant compromise of radial nerve motor function postoperatively (M3 and M2; the more compromised was preoperative injury). All patients recovered radial nerve neuropraxia within six weeks postoperatively. All fractures achieved union. The average anteroposterior and lateral axis were 175.0 ± 3.6 (168.0°-180.0°) and 177.5 ± 2.0 (173.0°-180.0°), respectively. No superficial or deep infection was reported. No cases of re-displacement of fracture, implant failure, or any other implant-related complication in follow-up were reported. No patient required plate withdrawal. Conclusion: The results of this study demonstrate that the posterior MIPO technique is a reliable option for treating distal third shaft humeral fractures. The radial nerve must be identified and protected in all cases to prevent palsy.

IGF-I deficiency and hearing loss: molecular clues and clinical implications.

Sensorineural hearing loss is a clinical heterogeneous disorder and a significant health-care problem with tremendous socio-economic impact. According to WHO, "Over 5% of the world's population has disabling hearing loss -328 million adults and 32 million children-". In children, early hearing loss affects language acquisition. Hearing deficits are generally associated with the loss of the sensory "hair" cells and/or neurons caused by primary genetic defects or secondary to environmental factors including infections, noise and ototoxic drugs. Hearing loss cannot be reversed and currently the available treatment is limited to hearing aids and cochlear implants. Studies are being conducted to develop alternative treatments combining both preventive and reparative strategies. Human insulin like growth factor (IGF) I deficiency is a rare disease associated with hearing loss, poor growth rates and mental retardation (ORPHA73272, OMIM608747). Similarly, lgf1-/- mice are dwarfs with poor survival rates and congenital profound sensorineural deafness. IGF-I is known to be a neuroprotective agent that maintains cellular metabolism, activates growth, proliferation and differentiation, and limits cell death. Here we will discuss the basic mechanisms underlying IGF-I actions in the auditory system and their clinical implications to pursue novel treatments to ameliorate hearing loss.

Straight antegrade humeral nailing and risk of iatrogenic injury of supraspinatus tendon footprint: An MRI study.

Background: Straight antegrade humeral nailing (SAHN) is associated with excellent clinical results in proximal humerus fractures. The optimal entry point is the top of the humeral head. However, the anatomy is variable, and the entry point can affect supraspinatus tendon footprint (SSP-F) or fracture reduction. The aim of this study was to analyze the relationship between the SSP-F and SAHN entry point by analyzing magnetic resonance imaging (MRI) studies of the humerus. Methods: In total 58 MRI studies of entire humerus were reviewed. The mean age was 51.6 ± 12.4 years, with 40 female patients. The distance between the SSP-F and the SAHN insertion point (critical distance: CD), the width of the footprint, and the neck-shaft angle (NSA) were measured. Univariate and multivariate analysis were performed. Results: The mean CD was 7.51 mm ± 2.81 (0-12.9 mm) with 51.7% of proximal humerus "critical type" (CD <8 mm). The CD was found to be lower in females, with no difference found with varying age (62.5% "critical type"). CD correlated with NSA (linear regression). "Critical type" correlated with female gender and NSA (logistic regression). Discussion: More than half of the humerus are "critical types" as to SAHN and may, therefore, be at risk for procedure-related complications.

The Reverse Shoulder Arthroplasty Angle in MRI: Impact of the Articular Cartilage in the Estimated Inclination of the Inferior Glenoid.

Purpose: To describe the reverse shoulder arthroplasty angle (RSA angle) in magnetic resonance imaging (MRI) and compare the angle formed using bony landmarks (Bony RSA angle or B-RSA angle) with another angle formed using the cartilage margin as reference (Cartilage RSA angle or C-RSA angle). Methods: Adult patients with a shoulder MRI obtained in our hospital between July 2020 and July 2021 were included. The C-RSA angle and B-RSA angle were measured. All images were independently assessed by 4 evaluators. Intraclass correlation coefficient (ICC) was determined for the B-RSA and C-RSA to evaluate interobserver agreement. Results: A total of 61 patients were included with a median age of 59 years (17-77). C-RSA angle was significantly higher than B-RSA (25.4° ± 0.7 vs 19.5° ± 0.7, respectively) with a P-value <.001. The overall agreement was considered "good" for C-RSA (ICC = 0.74 [95% CI 0.61-0.83]) and "excellent" for B-RSA angle (ICC = 0.76 [95% CI 0.65-0.85]). Conclusions: C-RSA angle is significantly higher than B-RSA angle. In cases without significant glenoid wear neglecting to account for the remaining articular cartilage at the inferior glenoid margin may result in superior inclination of standard surgical guides.

Predicting COVID-19 cases using SARS-CoV-2 RNA in air, surface swab and wastewater samples.

Genomic footprints of pathogens shed by infected individuals can be traced in environmental samples, which can serve as a noninvasive method of infectious disease surveillance. The research evaluates the efficacy of environmental monitoring of SARS-CoV-2 RNA in air, surface swabs and wastewater to predict COVID-19 cases. Using a prospective experimental design, air, surface swabs, and wastewater samples were collected from a college dormitory housing roughly 500 students from March to May 2021 at the University of Miami, Coral Gables, FL. Students were randomly screened for COVID-19 during the study period. SARS-CoV-2 concentration in environmental samples was quantified using Volcano 2nd Generation-qPCR. Descriptive analyses were conducted to examine the associations between time-lagged SARS-CoV-2 in environmental samples and COVID-19 cases. SARS-CoV-2 was detected in air, surface swab and wastewater samples on 52 (63.4 %), 40 (50.0 %) and 57 (68.6 %) days, respectively. On 19 (24 %) of 78 days SARS-CoV-2 was detected in all three sample types. COVID-19 cases were reported on 11 days during the study period and SARS-CoV-2 was also detected two days before the case diagnosis on all 11 (100 %), 9 (81.8 %) and 8 (72.7 %) days in air, surface swab and wastewater samples, respectively. SARS-CoV-2 detection in environmental samples was an indicator of the presence of local COVID-19 cases and a 3-day lead indicator for a potential outbreak at the dormitory building scale. Proactive environmental surveillance of SARS-CoV-2 or other pathogens in multiple environmental media has potential to guide targeted measures to contain and/or mitigate infectious disease outbreaks within communities.

Establishing safe zones to avoid nerve injury in the posterior minimally invasive plate osteosynthesis for humerus fractures: a magnetic resonance imaging study.

Background: Safety zones to avoid nerve injury at proximal incision of posterior minimally invasive plate osteosynthesis for humerus fracture have been scarcely studied. The purpose of this study was to describe the location of axillary and radial nerves (RN) in magnetic resonance imaging to establish safety zones. Methods: Fifty-two magnetic resonance imaging studies of the entire humerus were reviewed. The mean age was 50.6 ± 12.1 years, with 37 female patients. The distance of the axillary nerve (AN; distal portion, humeral midpoint) and RN (medial border, midpoint, and lateral border of the humerus) was measured in relation to the posterolateral acromion angle, acromioclavicular axis, and transepicondylar axis. Univariate analysis (Student's t test) and a multivariate analysis (linear regression) were performed. P values < .05 were considered significant. Results: The AN location at the humerus was 54.9 ± 6.4 mm (20.1% humeral length [HL]) in relation to posterolateral acromion angle and 63.2 ± 6.1 mm (23.2% HL) in relation to acromioclavicular axis. The RN location was 100.2 ± 17.1 mm (36.6% HL) at the humerus medial border, 118.0 ± 21.5 mm (43.1% HL) at the humerus midpoint, and 146.0 ± 24.4 mm (53.6% HL) at the humerus lateral border. In relation to transepicondylar axis, it was 175.4 ± 15.6 mm (64.3% HL), 156.0 ± 19.0 mm (57.2% HL), and 127.4 ± 21.2 mm (46.7% HL), respectively. Nerves location was related to HL, independent of gender. Conclusion: The main finding of our study is that the location of the AN and RN in relation to the humerus is related to the HL and can be used to predictably define the safe zones to avoid nerve injury in the proximal incision of posterior minimally invasive plate osteosynthesis for humerus fractures.

COVID-19 Prediction using Genomic Footprint of SARS-CoV-2 in Air, Surface Swab and Wastewater Samples.

Importance: Genomic footprints of pathogens shed by infected individuals can be traced in environmental samples. Analysis of these samples can be employed for noninvasive surveillance of infectious diseases. Objective: To evaluate the efficacy of environmental surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for predicting COVID-19 cases in a college dormitory. Design: Using a prospective experimental design, air, surface swabs, and wastewater samples were collected from a college dormitory from March to May 2021. Students were randomly screened for COVID-19 during the study period. SARS-CoV-2 in environmental samples was concentrated with electronegative filtration and quantified using Volcano 2 nd Generation-qPCR. Descriptive analyses were conducted to examine the associations between time-lagged SARS-CoV-2 in environmental samples and clinically diagnosed COVID-19 cases. Setting: This study was conducted in a residential dormitory at the University of Miami, Coral Gables campus, FL, USA. The dormitory housed about 500 students. Participants: Students from the dormitory were randomly screened, for COVID-19 for 2-3 days / week while entering or exiting the dormitory. Main Outcome: Clinically diagnosed COVID-19 cases were of our main interest. We hypothesized that SARS-CoV-2 detection in environmental samples was an indicator of the presence of local COVID-19 cases in the dormitory, and SARS-CoV-2 can be detected in the environmental samples several days prior to the clinical diagnosis of COVID-19 cases. Results: SARS-CoV-2 genomic footprints were detected in air, surface swab and wastewater samples on 52 (63.4%), 40 (50.0%) and 57 (68.6%) days, respectively, during the study period. On 19 (24%) of 78 days SARS-CoV-2 was detected in all three sample types. Clinically diagnosed COVID-19 cases were reported on 11 days during the study period and SARS-CoV-2 was also detected two days before the case diagnosis on all 11 (100%), 9 (81.8%) and 8 (72.7%) days in air, surface swab and wastewater samples, respectively. Conclusion: Proactive environmental surveillance of SARS-CoV-2 or other pathogens in a community/public setting has potential to guide targeted measures to contain and/or mitigate infectious disease outbreaks. Key Points: Question: How effective is environmental surveillance of SARS-CoV-2 in public places for early detection of COVID-19 cases in a community?Findings: All clinically confirmed COVID-19 cases were predicted with the aid of 2 day lagged SARS-CoV-2 in environmental samples in a college dormitory. However, the prediction efficiency varied by sample type: best prediction by air samples, followed by wastewater and surface swab samples. SARS-CoV-2 was also detected in these samples even on days without any reported cases of COVID-19, suggesting underreporting of COVID-19 cases.Meaning: SARS-CoV-2 can be detected in environmental samples several days prior to clinical reporting of COVID-19 cases. Thus, proactive environmental surveillance of microbiome in public places can serve as a mean for early detection of location-time specific outbreaks of infectious diseases. It can also be used for underreporting of infectious diseases.

In vitro inhibitory effect of aluminum phthalocyanine tetrasulfonate chloride against Leishmania (Viannia) Peruviana and Leishmania (Viannia) Braziliensis. / Efecto inhibitorio in vitro de la ftalocianina de aluminio tetrasulfonada clorada frente a Leishmania (Viannia) peruviana y Leishmania (Viannia) braziliensis.

OBJECTIVES: To evaluate the in vitro photodynamic activity of aluminum phthalocyanine tetrasulfonate chloride (AlPcClS4) on promastigotes and amastigotes of Leishmania (Viannia) peruviana and Leishmania (Viannia) braziliensis. MATERIALS AND METHODS: The activity of photodynamic therapy using AlPcClS4 on Leishmania promastigote and amastigotes was determined by the Methyl Thiazole Tetrazolium (MTT) colorimetric method and quantitative PCR, respectively. RESULTS: Photodynamic treatment showed an inhibitory effect on promastigotes, particularly on Leishmania (V.) peruviana, to a lesser extent on Leishmania (V.) braziliensis and also on intracellular forms of both species. At 24 hours post-radiation, using concentrations of 200 µM and 350 µM, the inhibitory effect on Leishmania (V.) peruviana was 72.9% and 73.9% respectively; at 96 hours the inhibitory effect was of 78.8% and 80.6%, respectively. Regarding intracellular forms, the inhibitory effect on Leishmania (V.) peruviana amastigotes was 57.8% at 72 hours post-treatment, using a concentration of 200 µM. The IC50 was 56.5, 50, 44 and 39.7 µM, at 24, 48, 72 and 96 hours post-radiation, respectively. CONCLUSIONS: Photodynamic therapy using AlPcClS4 against Leishmania species showed encouraging results, mainly on Leishmania (V.) peruviana, suggesting a potential use as an alternative or complement to the usual treatment of tegumentary leishmaniasis. However, new trials are still required to determine the selectivity index for the intracellular form of the parasite, and to develop methods to facilitate the efficient entry of the molecule into the host cell and the parasite.

OBJETIVOS: Evaluar la actividad fotodinámica in vitro de la ftalocianina de aluminio tetrasulfonada clorada (AlPcClS4) sobre promastigotes y amastigotes de Leishmania (Viannia) peruviana y Leishmania (Viannia) braziliensis. MATERIALES Y MÉTODOS: La actividad del tratamiento fotodinámico empleando AlPcClS4 sobre promastigotes y amastigotes de Leishmania fue determinada mediante el método colorimétrico Metil Tiazol Tetrazolium (MTT) y PCR cuantitativo, respectivamente. RESULTADOS: El tratamiento fotodinámico presentó un efecto inhibitorio sobre promastigotes, principalmente sobre Leishmania (V.) peruviana, en menor proporción sobre Leishmania (V.) braziliensis y sobre las formas intracelulares de ambas especies. En Leishmania (V.) peruviana, a las 24 horas posirradiación a 200 µM y 350 µM el efecto inhibitorio fue del 72,9% y 73,9%, respectivamente y a las 96 horas fue del 78,8% y 80,6%, respectivamente. En las formas intracelulares, empleando 200 µM y evaluado a las 72 horas postratamiento, se observó una inhibición del 57,8% de amastigotes de Leishmania (V.) peruviana. El IC50 fue del 56,5; 50; 44; y 39,7 µM, que corresponde a las 24, 48, 72 y 96 horas posirradiación, respectivamente. CONCLUSIONES: El tratamiento fotodinámico empleando AlPcClS4 frente a las especies de Leishmania presentó resultados alentadores principalmente sobre Leishmania (V.) peruviana, lo cual sugiere su potencial uso como alternativa o complemento del tratamiento convencional de la leishmaniasis tegumentaria. Sin embargo, aún se requiere continuar con nuevos ensayos para determinar el índice de selectividad sobre el parásito en su forma intracelular, y desarrollar estrategias que faciliten el ingreso eficiente de la molécula hacia la célula hospedera y al parásito.

Stevia rebaudiana Bertoni and Its Effects in Human Disease: Emphasizing Its Role in Inflammation, Atherosclerosis and Metabolic Syndrome.

PURPOSE OF REVIEW: Stevia rebaudiana Bertoni is a perennial shrub with zero calorie content that has been increasing in popularity for its potential use as an adjuvant in the treatment of obesity. The level of evidence supporting general benefits to human health is insufficient. We conducted a review of the literature summarizing the current knowledge and role in human disease. RECENT FINDINGS: Despite stevia's minimal systemic absorption, studies have been promising regarding its potential benefits against inflammation, carcinogenesis, atherosclerosis glucose control, and hypertension. On the other hand, the growing popularity of artificial sweeteners does not correlate with improved trends in obesity. An increased intake of artificial non-caloric sweeteners may not be associated with decreased intake of traditional sugar-sweetened beverages and foods. The effects of Stevia on weight change have been linked to bacteria in the intestinal microbiome, mainly by affecting Clostridium and Bacteroides sp. POPULATIONS: A growing body of evidence indicates that Stevia rebaudiana Bertoni is protective against malignant conversion by inhibition of DNA replication in human cancer cell growth in vitro. Consumption of Stevia has demonstrated to be generally safe in most reports. Further clinical studies are warranted to determine if regular consumption brings sustained benefits for human health.

SEM-EDS probing of morphological and physiological changes produced by a porphyrin photosensitizer in Psammobatis extenta electrocytes.

Morphological and physiological changes produced by the intracellular localization of an alkyl long-chain tetraphenylporphyrin photosensitizer in Psammobatis extenta electrocytes were studied by means of SEM-EDS. Immediately after photosensitizer penetration, electrocytes swell and their convex faces lose all invaginations. This effect is due to chloride and sodium ion flux into electrocytes, in accordance with energy dispersive X-ray microanalysis.