Clinical failure of dental ceramics is usually reported as partial fracture of the restoration (chipping) or as catastrophic fracture of the whole structure. In contrast to metals, ceramics are ...linear-elastic, brittle materials exhibiting extremely low damage tolerance to failure. Well documented clinical and lab reports have shown this fracture event often occurs at loads far below their fracture strength due to intrinsic fatigue degradation via slow crack growth or cyclic fatigue mechanisms. The presence and development of surface flaws have a dominant role in damage accumulation and lifetime reduction of ceramic structures.
This ADM guidance document aims to summarize the aspects related to fatigue degradation of dental ceramics, reviewing the concepts of fatigue testing and furthermore aims to provide practical guidance to young scientists entering into fatigue related research. The description of fatigue strength is always accompanied by a clear understanding of the underlying fracture mechanisms.
Mutations in the TRPC6 calcium channel (Transient receptor potential channel 6) gene have been associated with familiar forms of Focal and Segmental Glomerulosclerosis (FSGS) affecting children and ...adults. In addition, acquired glomerular diseases are associated with increased expression levels of TRPC6. However, the exact role of TRPC6 in the pathogenesis of FSGS remains to be elucidated. In this work we describe the generation and phenotypic characterization of three different transgenic mouse lines with podocyte-specific overexpression of the wild type or any of two mutant forms of Trpc6 (P111Q and E896K) previously related to FSGS. Consistent with the human phenotype a non-nephrotic range of albuminuria was detectable in almost all transgenic lines. The histological analysis demonstrated that the transgenic mice developed a kidney disease similar to human FSGS. Differences of 2-3 folds in the presence of glomerular lesions were found between the non transgenic and transgenic mice expressing Trpc6 in its wild type or mutant forms specifically in podocytes. Electron microscopy of glomerulus from transgenic mice showed extensive podocyte foot process effacement. We conclude that overexpression of Trpc6 (wild type or mutated) in podocytes is sufficient to cause a kidney disease consistent with FSGS. Our results contribute to reinforce the central role of podocytes in the etiology of FSGS. These mice constitute an important new model in which to study future therapies and outcomes of this complex disease.
The neurodiagnostic criteria of Leigh syndrome have not yet been clearly redefined based on the expanding of molecular etiologies. We aimed to analyze 20 years of clinical, genetic, and magnetic ...resonance studies from our Leigh syndrome cohort to provide a detailed description of central nervous system lesions in Leigh syndrome and their biological evolution in view of their genetic and clinical findings. Our study adds new neurodiagnostic insights to the current knowledge of Leigh syndrome, including association with overlapping syndromes, and the correlation of pathogenic genetic variants with neuroimaging phenotypes. ANN NEUROL 2020;88:218–232.
Abstract
Objectives
To estimate the cost of six different techniques used to treat Genital Warts and the annual average cost of treating a typical GW patient in Peru. To estimate the annual economic ...burden diagnosing and treating GW in the Peruvian public healthcare system.
Methods
We developed a prevalence-based, cost-of-illness study from the provider’s perspective, the healthcare facilities under the purview of Peruvian Ministry of Health. We used an activity-based costing approach. We conducted primary data collection in three regions in Peru and supplemented it with governmental data. Uncertainty of the costing estimates was assessed via Monte Carlo simulations. We estimated the average cost and associated confidence intervals for six treatment options – three topical and three surgical – and the overall cost per patient.
Results
The average treatment cost per patient was 59.9USD (95 %CI 45.5, 77.6). Given a population of 18.4 million adults between 18 and 60 years of age and a GW prevalence of 2.28 %, the annual cost of treating GW was 25.1 million USD (uncertainty interval 16.9, 36.6).
Conclusions
This study provides the first quantification of the economic burden of treating genital warts in Peru and one of the few in Latin America. The costing data did not include other healthcare providers or out-of-pocket expenditures, and hence we present a conservative estimate of the COI of GW in Peru. Our findings bring attention to the financial burden of treating GW, a vaccine-preventable disease.
Oligosaccharides are the third most abundant component in human milk. They are a potential protective agent against neonatal sepsis.
We aimed to explore the association between human milk ...oligosaccharides (HMOs) and late-onset sepsis in very-low-birth-weight infants, and to describe the composition and characteristics of HMOs in Peruvian mothers of these infants.
This is a secondary data analysis of a randomized clinical trial. We conducted a retrospective cohort study of mothers and their very-low-birth-weight (<1500 g) infants with ≥1 milk sample and follow-up data for >30 d. HMOs were measured by high performance liquid chromatography (HPLC). We used factor analysis and the Mantel–Cox test to explore the association between HMOs and late-onset neonatal sepsis.
We included 153 mother–infant pairs and 208 milk samples. Overall, the frequency of the secretor phenotype was 93%. Secretors and nonsecretors were defined by the presence and near-absence of α1-2-fucosylated HMOs, respectively. The most abundant oligosaccharides were 2’-fucosyllactose, lacto-N-fucopentaose (LNFP) I, and difucosyllacto-N-tetraose in secretors and lacto-N-tetraose and LNFP II in nonsecretors. Secretors had higher amounts of total oligosaccharides than nonsecretors (11.45 g/L; IQR: 0.773 g/L compared with 8.04 g/L; IQR: 0.449 g/L). Mature milk samples were more diverse in terms of HMOs than colostrum (Simpson’s Reciprocal Diversity Index). We found an association of factor 3 in colostrum with a reduced risk of late-onset sepsis (HR: 0.63; 95% CI: 0.41, 0.97). Fucosyl-disialyllacto-N-hexose (FDSLNH) was the only oligosaccharide correlated to factor 3.
These findings suggest that concentrations of different HMOs vary from one individual to another according to their lactation period and secretor status. We also found that FDSLNH might protect infants with very low birth weight from late-onset neonatal sepsis. Confirming this association could prove 1 more mechanism by which human milk protects infants against infections and open the door to clinical applications of HMOs. This trial was registered at clinicaltrials.gov as NCT01525316.
The primary objective is to determine the effect of a daily dose of ivermectin administered in three consecutive days to non-severe COVID-19 patients with no more than 96 hours of symptoms, on the ...detection of SARS-CoV-2 RNA by PCR from nasopharyngeal swabs at day seven post-treatment initiation. The secondary objectives are: 1. To assess the efficacy of ivermectin to reduce the SARS-CoV-2 viral load in the nasopharyngeal swab on days 4, 7, 14 and 21 post-treatment initiation 2. To assess the efficacy of ivermectin on the improvement of symptoms 3. To assess the proportion of seroconversions at day 21 4. To assess the safety of ivermectin at the proposed dose 5. To determine the magnitude of the immune response against SARS-CoV-2 6. To assess correlation of the presence of intestinal helminths on participants on baseline and day 14 with COVID-19 progression and treatment.
SAINT PERU is a triple-blinded, randomized, placebo-controlled trial with two parallel arms to evaluate the efficacy of ivermectin in negativizing nasopharyngeal PCR in patients with SARS-CoV-2 infection.
The trial is conducted in two national hospitals in Lima-Peru. The study population is patients with a positive PCR test for SARS-CoV-2 in a nasopharyngeal specimen, symptomatic for 96 hours or less, with non-severe COVID-19 disease at baseline, regardless of the presence of risk factors for progression to severity. The study will not include pregnant women or minors (17 years old or younger). Inclusion criteria 1. COVID-19 symptomatology (cough, fever, anosmia, etc.) lasting no more than 96 hours, with a positive nasopharyngeal swab PCR test for SARS-CoV-2. 2. 18 years or older. 3. No use of ivermectin in the month prior to the visit. 4. No known history of ivermectin allergy. 5. Capable to give informed consent. 6. Not current use of CYP 3A4 or P-gp inhibitor drugs such as quinidine, amiodarone, diltiazem, spironolactone, verapamil, clarithromycin, erythromycin, itraconazole, ketoconazole, cyclosporine, tacrolimus, indinavir, ritonavir, cobicistat or critical CYP3A4 substrate drugs such as warfarin. Exclusion criteria 1. COVID-19 pneumonia diagnosed by the attending physician (oxygen saturation < 95% or lung examination) 2. Positive pregnancy test for women at childbearing age. 3. Positive IgG against SARS-CoV-2 by rapid diagnostic test at screening. Participants will be recruited by the investigators at the emergency services of the study sites. They are expected to remain in the trial for a period of 21 days. Follow-up visits will be conducted by the trial medical staff at the participant's home or at a hospital in case of hospitalization. Follow-up visits will assess clinical and laboratory parameters of the patients.
Ivermectin (300 mcg/kg) or placebo will be administered in one daily dose for three consecutive days. Currently, there is no solid data on the efficacy of ivermectin against the virus in vivo; therefore the use of placebo in the control group is ethically justified.
Primary Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment. Secondary 1. Mean viral load as determined by PCR cycle threshold (Ct) on days 4, 7, 14, and 21 2. Proportion of patients with fever and cough at days 4, 7, 14, and 21 as well as proportion of patients progressing to severe disease or death during the trial 2. Proportion of patients with a positive rapid diagnostic test at day 21 3. Proportion of drug-related adverse events during the trial 4. Median levels of IgG, IgM, IgA measured by Luminex RANDOMIZATION: Participants will be randomized to receive one dose of 300 mcg/kg ivermectin or placebo daily for three consecutive days. The epidemiologist will generate a list of correlative numbers, in randomized blocks of size 4, with the assignment to the treatment groups (a and b). The randomization list will be kept in an encrypted file accessible only to the trial statistician. This list will be handed directly to the pharmacist. Independently, the principal investigator will randomly assign the intervention (ivermectin) to one of the two groups (a or b) by tossing a coin, and will inform the pharmacist of the result of this process. The pharmacist will prepare and label the treatment vials according to the randomization list prepared by the epidemiologist and the treatment assignment given by the principal investigator. Eligible patients will be allocated in a 1:1 ratio using this randomization list.
The clinical trial team, the statistician, and the patients will be blinded as to arm allocation. The vials with placebo will be visibly identical to the ones with the active drug. Treatment will be administered by staff not involved in the clinical care or participant's follow up.
The planned sample size is 186 SARS-CoV-2 PCR positive patients: 93 patients to treatment and 93 to the placebo group.
Current protocol version: 2.0 dated January 15
, 2021. Recruitment started on Aug 29
, 2020. Recruitment is expected to be completed April 30
2021.
"Ensayo Clínico aleatorizado de Fase IIa para comparar la efectividad de la ivermectina versus placebo en la negativización del PCR en pacientes en fase temprana de COVID-19" Peru National Health Institute REPEC with number: PER-034-20 , registered July 17
2020 (National Peruvian Registration before the first participant enrolled). "Randomized Phase IIA Clinical Trial to Evaluate the Efficacy of Ivermectin to Obtain Negative PCR Results in Patients With Early Phase COVID-19" Clinicaltrials.gov: NCT04635943 , retrospectively registered in November 19
2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
Objectives/Hypothesis
Releasing the nasoseptal flap (NSF) pedicle from the sphenopalatine artery (SPA) foramen may considerably improve flap reach and surface area. Our objectives were quantify ...increases in pedicle length and NSF reach through extended pedicle dissection into the pterygopalatine fossa (PPF) through cadaveric dissections and present clinical applications.
Study Design
Anatomical study and retrospective clinical cohort study.
Methods
Twelve cadaveric dissections were performed. Following standard NSF harvest, the distance from the anterior edge of the flap to the anterior nasal spine while pulling the flap anteriorly was measured. As dissection into the SPA foramen and PPF continued, similar interval measurements were completed in four stages after release from the SPA foramen, release of the internal maxillary artery (IMAX), and transection of the descending palatine artery (DPA). The extended pedicle dissection technique was performed in seven consecutive patients for a variety of different pathologies.
Results
The mean length of the NSF from the anterior nasal spine and maximum flap reach were 1.91 ± 0.40 cm/9.3 ± 0.39 cm following standard harvest, 2.52 ± 0.61 cm/9.75±1.06 cm following SPA foramen release, 4.93 ± 0.89 cm/12.16 ± 0.54 cm following full IMAX dissection, and 6.18 ± 0.68 cm/13.41 ± 0.75 cm following DPA transection. No flap dehiscence or necrosis was observed in all seven surgical patients.
Conclusions
Extended pedicle dissection of the NSF to the SPA/IMAX markedly improves the potential length and reach of the flap. This technique may provide a feasible option for reconstruction of large anterior skull base and craniocervical junction defects. Seven successful cases are presented here, but further studies with larger series are warranted to validate findings in a clinical setting.
Level of Evidence
4 Laryngoscope, 130:18–24, 2020
To determine the effect of bovine lactoferrin on prevention of late-onset sepsis (LOS) and neurodevelopment delay.
Randomized, double-blind, controlled trial in neonates with a birth weight of ...500-2000 g in 3 neonatal units in Lima, Peru, comparing bovine lactoferrin 200 mg/kg/day with placebo administered for 8 weeks. The primary outcome was the first episode of culture-proven LOS or sepsis-associated death. Neurodevelopment delay was assessed by the Mullen Scales at 24 months corrected age.
Of the 414 infants enrolled, 209 received bovine lactoferrin and 205 received placebo. LOS or sepsis-associated death occurred in 22 infants (10.5%) in the bovine lactoferrin group vs 30 (14.6%) in the placebo group; there was no difference after adjusting for hospital and birth weight; hazard ratio 0.73 (95% CI, 0.42-1.26). For infants with birth weights of <1500 g the hazard ratio was 0.69 (95% CI, 0.39-1.25). The mean age-adjusted normalized Mullen composite score at 24 months was 83.3 ± 13.6 in the bovine lactoferrin group vs 82.6 ± 13.1 in the placebo group. Growth outcomes and rehospitalization rates during the 2-year follow-up were similar in both groups, except for significantly less bronchiolitis in the bovine lactoferrin group (rate ratio, 0.34; 95% CI, 0.14-0.86).
Supplementation with bovine lactoferrin did not decrease the incidence of sepsis in infants with birth weights of <2000 g. Growth and neurodevelopment outcomes at 24 months of age were similar. Neonatal bovine lactoferrin supplementation had no adverse effects.
ClinicalTrials.gov: NCT01525316.
The Loreto region of the Peruvian Amazon faces many obstacles to health care delivery. The majority of the population is river-bound and lives below the poverty line, with some of the worst health ...indicators in Peru. To overcome these barriers and fill a gap in health services, an NGO-based provider known as the Vine Trust has been providing care since 2001 via a mobile ship clinic called the Amazon Hope. This study presents an assessment of the Amazon Hope, first reporting health indicators of the program´s catchment area, services provided, and program utilization. It then describes perceptions of the program by community members and health workers, the program's strengths and weaknesses in contributing to health service delivery, and provides recommendations addressing limitations. The qualitative analysis included 20 key informant interviews with community members and health service providers. In the quantitative analysis, 4,949 residents of the catchment area were surveyed about medical histories, experiences with the program, and suggestions for improvement. The survey showed poor indicators for reproductive health. The AH clinic was the main provider of health care among those surveyed. Community members reported satisfaction with the program's quality of care, and health workers felt the program provided a unique and necessary service. However, community members requested prior notification and additional services, while health workers described misunderstandings in community-tailored care, and difficulties with continuity of care and coordination. Data show that the program has been successful in providing quality health care to a population but has room to improve in its health service delivery. Suggested improvements are provided based on participant suggestions and relevant literature. The study sheds light on the important role of mobile clinics in Peru, and the methodology can serve as a model for assessing the role of mobile clinics in other remote settings.
PDF
