Transtibial Lateral Meniscal Root Repair Technique to Appose Remnant Root With Torn Body: The Double Compression Knot.

Anterior cruciate ligament reconstructions are often performed with associated procedures, most commonly for associated meniscal tears. The lateral meniscal root tear is a commonly associated injury, which increases rotational instability and results in altered tibiofemoral biomechanics. Lateral meniscectomy results in poorer functional and long-term outcomes, making repair vital. The position of the lateral root tear makes its repair technique complicated. Because of the proximity to vessels posteriorly, the all-inside technique is considered potentially unsafe, and current transtibial repair techniques fail to appose the body with the root remnant. In the lineage of Laprade, who proclaimed the use of a transtibial suture for radial tears elsewhere in the knee in order to reduce the shear force, we describe a transtibial technique that optimizes meniscal apposition, theoretically improving the repair biomechanics and is technically easier to perform in comparison to suture hook techniques with one tunnel and one suture.

Oxidative genomic damage in humans exposed to high indoor radon levels in Northeast Brazil.

Radon gas inhalation is the main source of exposure to ionizing radiation by humans. There is still lack in knowledge concerning the chronic and indirect effects of exposure to this carcinogenic factor. Therefore, the aim of this work is to analyze the levels of oxidative genomic damage in inhabitants of a medium-high background radiation area (HBRA) (N = 82) in Northeastern Brazil and compare them with people living in a low background radiation area (LBRA) (N = 46). 8-hydroxy-2-deoxyguanosine (8-OHdG) was quantified in urine, Ser326Cys polymorphism was determined in the hOGG1 gene and indoor radon was measured. HBRA houses had 6.5 times higher indoor radon levels than those from LBRA (p-value < 0.001). The 8-OHdG mean (95% confidence interval) were significantly different, 8.42 (5.98-11.9) ng/mg creatinine and 29.91 (23.37-38.30) ng/mg creatinine for LBRA and HBRA, respectively. The variables representing lifestyle and environmental and occupational exposures did not have a significant association with oxidized guanosine concentrations. On the other hand, lower 8-OHdG values were observed in subjects that had one mutant allele (326Cys) in the hOGG1 gene than those who had both wild alleles (Ser/Ser (p-value < 0.05). It can be concluded that high radon levels have significantly influenced the genome oxidative metabolism and hOGG1 gene polymorphism would mediate the observed biological response.

Positive end-expiratory pressure induced changes in airway driving pressure in mechanically ventilated COVID-19 Acute Respiratory Distress Syndrome patients.

BACKGROUND: The profile of changes in airway driving pressure (dPaw) induced by positive-end expiratory pressure (PEEP) might aid for individualized protective ventilation. Our aim was to describe the dPaw versus PEEP curves behavior in ARDS from COVID-19 patients. METHODS: Patients admitted in three hospitals were ventilated with fraction of inspired oxygen (FiO2) and PEEP initially adjusted by oxygenation-based table. Thereafter, PEEP was reduced from 20 until 6 cmH2O while dPaw was stepwise recorded and the lowest PEEP that minimized dPaw (PEEPmin_dPaw) was assessed. Each dPaw vs PEEP curve was classified as J-shaped, inverted-J-shaped, or U-shaped according to the difference between the minimum dPaw and the dPaw at the lowest and highest PEEP. In one hospital, hyperdistention and collapse at each PEEP were assessed by electrical impedance tomography (EIT). RESULTS: 184 patients (41 including EIT) were studied. 126 patients (68%) exhibited a J-shaped dPaw vs PEEP profile (PEEPmin_dPaw of 7.5 ± 1.9 cmH2O). 40 patients (22%) presented a U (PEEPmin_dPaw of 12.2 ± 2.6 cmH2O) and 18 (10%) an inverted-J profile (PEEPmin_dPaw of 14,6 ± 2.3 cmH2O). Patients with inverted-J profiles had significant higher body mass index (BMI) and lower baseline partial pressure of arterial oxygen/FiO2 ratio. PEEPmin_dPaw was associated with lower fractions of both alveolar collapse and hyperinflation. CONCLUSIONS: A PEEP adjustment procedure based on PEEP-induced changes in dPaw is feasible and may aid in individualized PEEP for protective ventilation. The PEEP required to minimize driving pressure was influenced by BMI and was low in the majority of patients.

Safety and immunogenicity of an investigational quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACYW-TT) co-administered with routine pediatric vaccines in infants and toddlers: A Phase II study.

BACKGROUND: The MenACYW-TT conjugate vaccine is approved for prevention of invasive meningococcal disease (IMD) as a single dose in individuals ≥2 years of age in the United States and ≥12 months in EU and some other countries. This Phase II study evaluated the safety and immunogenicity of this vaccine and of concomitant pediatric vaccines in infants/toddlers (6 weeks-15 months of age). METHODS: Five schedules of the MenACYW-TT conjugate vaccine were evaluated in the United States: 2, 4, 6, and 12 months; 2, 4, 6, and 15 months; 2, 4, and 12 months; 6 and 12 months; and 12 months alone. Routine pediatric vaccines (DTaP-IPV/Hib, PCV7/PCV13, MMR, and varicella) were administered per approved schedules. Proportions of participants with serum bactericidal antibodyassay with human complement (hSBA) titers ≥1:4 and ≥1:8, SBA with baby rabbit complement (rSBA) titers ≥1:8 and ≥1:128, and immune responses against concomitant vaccines were determined. RESULTS: Tenderness and irritability were the most frequent solicited injection site and systemic reactions. Similar proportions of participants achieved an hSBA titer ≥1:8 for all four serogroups regardless of whether 2 or 3 doses were administered in the first year of life. Following a second-year dose, 91-100% of participants achieved the threshold for all 4 serogroups in all schedules regardless of the number of doses in the first year of life. Similar responses were seen with rSBA. Immunogenicity and safety profile of concomitant vaccines was similar whether the MenACYW-TT conjugate vaccine was administered or not. CONCLUSION: MenACYW-TT conjugate vaccine administered with pediatric vaccines is safe and immunogenic regardless of the schedule and does not affect the immunogenicity or safety of the concomitant vaccines. CLINICAL TRIAL REGISTRY: NCT01049035.

Natural radioactivity in Brazil: a systematic review.

Natural radioactivity is a public health concern worldwide. Its deleterious effects are largely associated with emitting ionizing particles which generate innumerable toxicological consequences to human being. The present study aimed to describe the research state of the art on natural radioactivity in Brazil through a systematic review limited to articles published in the twenty-first century in the PubMed, SciELO, Lilacs, and Google Scholar databases. A total of 55 research articles were considered for this purpose. Based on the collected sample types, the radiation analysis in most of the scientific reports was performed on solid samples (soil/sediment/rocks), followed by water and air. In fact, most of the available information came from geological studies. A wide range of concentrations and a variety of radionuclides have been assessed, with radium being the most cited. Most of the studies described radiation levels above the international guidelines, and consider the Brazilian territory as a high natural background radiation region (HNBR). In comparison with other HNBR areas, the scientific information about the related risks to human health is still scarce. There is uncertainty about the real impact of natural radioactivity on human health, as there is a lack of scientific information for most of the country about this issue. The analysis and comparison of the available information highlights the potential risks linked to natural radioactivity and the need to incorporate suitable environmental management policies about this issue.

Evaluation of a Hexavalent-Pentavalent-Hexavalent Infant Primary Vaccination Series Followed by a Pentavalent Booster Vaccine in Healthy Infants and Toddlers.

BACKGROUND: This study assessed a pediatric mixed hexavalent diphtheria (D)-tetanus (T)-acellular pertussis (aP)-inactivated poliovirus (IPV)-hepatitis B (HB)-Haemophilus influenzae b [polyribosylribitol phosphate (PRP-T)]-pentavalent (DTaP-IPV//PRP-T)-hexavalent primary series schedule followed by a pentavalent booster. METHODS: Healthy infants (N = 265) who had received a prior HB vaccination received a fully liquid, hexavalent vaccine (DTaP-IPV-HB-PRP-T) at 2 and 6 months of age and a reconstituted pentavalent vaccine (DTaP-IPV//PRP-T) at 4 months of age. Coadministered vaccines were pneumococcal vaccine at 2 and 4 months (and optionally at 6 months of age), rotavirus vaccine at 2, 4, 6 months and meningococcal serogroup C vaccine at 2 months. At 18 months, participants received DTaP-IPV//PRP-T and pneumococcal vaccine boosters. Immunogenicity was assessed using validated assays and safety by parental reports. RESULTS: For the hexavalent and pentavalent vaccines, the primary series and booster immune responses in terms of seroprotection and vaccine response rates were high for all antigens (generally > 99% and > 95% for the primary series and booster, respectively) and prebooster antibody persistence was good for all antigens (in particular, 92.4% of participants had prebooster anti-HB antibody ≥ 10 mIU/mL). The incidence of solicited reactions was lower after the booster vaccination (56.9%-73.1%) than the primary series (76.6%-97.4%); there were few vaccine-related unsolicited adverse events (1.9% and 1.5% for the primary series and booster, respectively), none led to participant discontinuation and none was serious. CONCLUSIONS: This study provides data that allow recommending authorities to consider the use of a sequential hexavalent-pentavalent-hexavalent primary vaccination series followed by a pentavalent booster in coadministration with other common childhood vaccines.

Concomitant administration of a fully liquid ready-to-use DTaP-IPV-HB-PRP-T hexavalent vaccine with a meningococcal ACWY conjugate vaccine in toddlers.

Invasive meningococcal disease caused by Neisseria meningitidis is a life-threatening disease. Several countries now include meningococcal serogroup C (MenC) conjugate and, more recently, a meningococcal serogroup ACWY conjugate (MenACWY) vaccination in their national immunization schedules. DTaP-IPV-HB-PRP-T is a hexavalent vaccine that provides protection against six diseases. The phase III, open-label, randomised, multicentre study enrolled healthy toddlers who received the DTaP-IPV-HB-PRP-T vaccine (at 2, 3 and 4 months) with or without a MenC vaccine (at 2 and 4 months) in the primary series study. At 12 months of age, 312 toddlers were randomised to receive DTaP-IPV-HB-PRP-T co-administered with MenACWY-TT vaccine (Group A; n = 104); DTaP-IPV-HB-PRP-T vaccine alone (Group B; n = 105); or MenACWY-TT vaccine alone (Group C; n = 103). At 12 months of age, there were no notable differences in terms of antibody persistence for any DTaP-IPV-HB-PRP-T vaccine antigen, whether MenC-TT conjugate vaccine was co-administered or not during the primary series. Following booster vaccination, immune responses to DTaP-IPV-HB-PRP-T and MenACWY-TT vaccines were not affected by co-administration. One month after vaccination, the immune responses elicited by both vaccines were high, whether administered concomitantly or separately. The administration of MenC vaccine during infancy did not preclude the use of a MenACWY-TT vaccine for booster vaccination. Even though the reactogenicity after co-administration was somewhat higher, the results of this study support the concomitant administration of the DTaP-IPV-HB-PRP-T vaccine with a MenACWY-TT conjugate vaccine when given from 12 months of age. The clinical trial registration numbers are: clinicaltrial.gov: NCT01839175; EudraCT: 2012-005547-24.

Diosgenin induces genotoxic and mutagenic effects on HepG2 cells.

Yam roots and other plants from Dioscorea genus have cultural, nutritional and economic importance to tropical and subtropical regions and have a great amount of diosgenin in its composition. In the present study the cytotoxic, genotoxic and mutagenic potential of diosgenin on HepG2 cells was investigated. Cytotoxicity was assessed using MTT and clonogenic assay. Genotoxic and mutagenic effects were performed using single cell gel electrophoresis and cytokinesis-block micronucleus assay, respectively. A reduction on cell viability was observed due to diosgenin treatment at concentrations higher than 30 µM. A genotoxic effect was shown by comet assay and CBMN. Besides, an increase in micronucleus frequency along with a significant cytostatic effect were observed. Diosgenin elicited DNA damage on HepG2 cells which could not be efficiently repaired contributing to the mutagenic effect observed. Those results suggest that diosgenin deleterious effect could take place through genetic instability, fact that affects the normal cell cycle, leading to cell's death.

Persistence of hepatitis B immune memory until 9-10 years of age following hepatitis B vaccination at birth and DTaP-IPV-HB-PRP∼T vaccination at 2, 4 and 6 months.

OBJECTIVE: To evaluate the long-term persistence of anti-hepatitis B surface (HBs) antibodies and the response to a HB challenge re-vaccination in children who had received a primary series of DTaP-IPV-HB-PRP∼T (Hexaxim™) or DTaP-IPV-HB/PRP∼T (Infanrix hexa™). METHODS: Two cohorts of participants who had previously received HB vaccine at birth followed by either DTaP-IPV-HB-PRP∼T or DTaP-IPV-HB/PRP∼T co-administered with PCV7 at 2, 4, 6 months of age in a randomized, Phase III, observer-blind study in Thailand, were followed up for anti-HBs antibodies (geometric mean concentrations [GMCs] and seroprotection [SP] rate [% of participants with a titer ≥10 mIU/mL]) at 12-18 months of age and 9-10 years of age. A monovalent HB challenge re-vaccination was administered at 9-10 years of age and the anamnestic response was evaluated. RESULTS: Anti-HBs GMCs and SP rates in the DTaP-IPV-HB-PRP∼T and DTaP-IPV-HB/PRP∼T groups were high and similar post-primary vaccination series (2477 mIU/mL and 99.5% and 2442 mIU/mL and 99.5%, respectively) and declined to a similar extent in each group at 12-18 months (154.5 mIU/mL and 90.8% and 162.3 mIU/mL and 96.5%, respectively). Antibody levels further declined at 9-10 years of age (13.3 mIU/mL and 49.3% and 8.0 mIU/mL and 42.9%) and a strong anamnestic response occurred in each group post-HB challenge re-vaccination (92.8% and 98.7%, respectively). CONCLUSION: The kinetics of long-term anti-HBs antibody persistence were similar following a primary series of DTaP-IPV-HB-PRP∼T or DTaP-IPV-HB/PRP∼T. The response to a subsequent HB challenge re-vaccination was strong and similar in each group, demonstrating persisting immune memory.

Concomitant administration of a fully liquid, ready-to-use DTaP-IPV-HB-PRP-T hexavalent vaccine with a meningococcal serogroup C conjugate vaccine in infants.

DTaP-IPV-HB-PRP-T or hexavalent vaccines are indicated for primary and booster vaccination of infants and toddlers against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b (Hib). The present study evaluates the safety and immunogenicity of a ready-to-use hexavalent vaccine when co-administered with a meningococcal serogroup C conjugate (MenC) vaccine in infants. This was a phase III, open-label, randomised, multicentre study conducted in Finland. Healthy infants, aged 46-74days (n=350), were randomised in a ratio of 1:1 to receive DTaP-IPV-HB-PRP-T vaccine at two, three and four months, either with a MenC vaccine co-administered at two and four months (Group 1; n=175) or without MenC vaccine (Group 2; n=175). All infants also received routine rotavirus and 13-valent pneumococcal conjugate vaccines. The proportion of participants with an anti-HBs concentration ⩾10mIU/mL assessed one month after the third dose of DTaP-IPV-HB-PRP-T vaccine was 97.5% [95%CI: 93.1-99.3] in the coadministration group and 96.1% [95%CI: 91.8-98.6] in the group without MenC vaccine. The proportion of participants with an anti-MenC SBA titre ⩾8 assessed one month after the second dose of MenC vaccine was 100% in the coadministration group. Both primary objectives were achieved. Secondary immunogenicity and safety analyses showed that co-administration of DTaP-IPV-HB-PRP-T and MenC vaccines did not impact the immune response to the antigens of each of the two vaccines. All vaccines were well tolerated and the safety profile of DTaP-IPV-HB-PRP-T vaccine was similar in both groups. ClinicalTrials.gov identifier: NCT01839175; EudraCT number: 2012-005547-24.

Chromosomal characterization of cryopreserved mesenchymal stem cells from the human subendothelium umbilical cord vein.

AIMS: To conduct a morphological, functional and chromosomal characterization of mesenchymal stem cell populations from the human subendothelium umbilical cord vein after cryopreservation. MATERIAL & METHODS: Five human umbilical cords were processed in order to obtain mesenchymal stem cells. Flow cytometry, differentiation assays and cytogenetic analysis were carried out before and after the cryopreservation process. RESULTS: Flow cytometry revealed that CD105, CD73 and CD90 markers were expressed by the cells, which lacked the expression of hematopoietic lineage markers, such as CD14, CD34 and CD45. The mesenchymal stem cells demonstrated capacity for osteogenic, adipogenic and chondrogenic differentiation. Chromosome analysis showed no clonal chromosome changes in the cells in either situation. However, a significant number of nonclonal chromosomal aberrations were apparent after cryopreservation, including monosomies and structural changes. Cells isolated from one umbilical cord exhibited a rare balanced paracentric inversion, likely a cytogenetic constitutional alteration. This was present both before and after experimental procedures. CONCLUSION: These findings show that using mesenchymal stem cells for clinical approaches requires careful investigation and sensitive tests in order to ensure cellular therapy biosafety.