Educational interventions in pharmacovigilance to improve the knowledge, attitude and the report of adverse drug reactions in healthcare professionals: Systematic Review and Meta-analysis.

OBJECTIVES: Underreporting of adverse drug reactions (ADRs) limits and delays the detection of signs. The aim of this systematic review with meta-analyses was to synthesize the evidence of educational interventions (EIs) efficacy in health professionals to increase ADR reporting, attitudes, and knowledge of pharmacovigilance. EVIDENCE ACQUISITION: A systematic literature review was carried out to identify randomized clinical trials evaluating the efficacy of EI in pharmacovigilance in health professionals to improve ADR reports, knowledge, and attitude toward pharmacovigilance. ADR reports were pooled by calculating Odds Ratio (OR) with a 95% confidence interval (95%CI), while pharmacovigilance knowledge and attitude were pooled by calculating a mean difference (MD) with 95%CI. In addition, the subanalysis was performed by EI type. Meta-analysis was performed with RevMan 5.4 software. PROSPERO registry CRD42021254270. RESULTS: Eight hundred seventy-five articles were identified as potentially relevant, and 11 were included in the systematic review. Metanalysis showed that EI increased ADR reporting in comparison with control group (OR = 4.74, [95%CI, 2.46 to 9.12], I2 = 93%, 5 studies). In subgroup analysis, the workshops (OR = 6.26, [95%CI, 4.03 to 9.73], I2 = 57%, 3 studies) increased ADR reporting more than telephone-based interventions (OR = 2.59, [95%CI, 0.77 to 8.73], I2 = 29%, 2 studies) or combined interventions (OR = 5.14, [95%CI, 0.97 to 27.26], I2 = 93%, 3 studies). No difference was observed in pharmacovigilance knowledge. However, the subanalysis revealed that workshops increase pharmacovigilance knowledge (SMD = 1.85 [95%CI, 1.44 to 2.27], 1 study). Only one study evaluated ADR reporting attitude among participants and showed a positive effect after the intervention. CONCLUSION: EI improves ADR reports and increases pharmacovigilance knowledge. Workshops are the most effective EI to increase ADR reporting.

Sex-biased parental investment and female wealth accumulation in ancient California.

OBJECTIVES: The mortuary record at Middle Period site Kalawwasa Rummeytak (CA-SCL-134) (2600-1225 cal BP) in California's southern Santa Clara Valley shows pronounced wealth inequality; Olivella shell bead wealth, as well as other grave goods, are concentrated in the burials of several older adult females. The concentration of wealth among women, along with regional strontium isotopic evidence of male-biased residential shifts in early adulthood, suggests a matrilineal kinship system that practiced matrilocal post-marital residence patterns. We suggest local resource enhancement effects incentivized keeping women in their natal communities and investing more in female offspring. MATERIALS AND METHODS: With the consent of, and in collaboration with, the Muwekma Ohlone Tribe of the San Francisco Bay Area, this paper employs isotopic analysis (δ15 N and δ13 C, 86 Sr/87 Sr) to examine duration of exclusive breastfeeding, weaning age (complete cessation of breastmilk consumption), early childhood diet, and lifetime residential mobility of individuals interred at Kalawwasa Rummeytak to test the assumption that the site inhabitants favored matrilocality and that female offspring received greater levels of investment in groups with female wealth/status attainment. First molars, third molars, and bone was sampled from 22 individuals. RESULTS: The average weaning age for females at Kalawwasa Rummeytak is 36.3 months ± 9.7 (1 SD), or just over 3 years. The average weaning age for males is 31.2 ± 7.9 months (1 SD), or about 2.6 years. Infants at the site were provisioned with supplemental foods dominated by C3 plants and terrestrial herbivores, as well as anadromous fish. After weaning, individuals consumed a diet dominated by acorns, C3 plants, and terrestrial herbivores, with periodic inclusion of anadromous fish. 30% of the sampled population of females exhibit local first molar 87 Sr/86 Sr values, suggesting that Kalawwasa Rummeytak is their natal community. None of the males interred at the site are locals. DISCUSSION: Despite the small sample size often unavoidable in archaeological contexts, we find possible female-biased parental investment strategies. Cessation of breastfeeding (weaning) was, on average, 5 months earlier for males compared to females. There are no differences between females and males in the consumption of supplemental or post-weaning foods. Strontium data suggest a flexible postmarital residence system that favored matrilocality. This may have incentivized greater investment in female offspring.

κO-SrVIA Conopeptide, a Novel Inhibitor Peptide for Two Members of the Human EAG Potassium Channel Family.

The first conotoxin affecting the voltage-gated potassium channels of the EAG family was identified and characterized from the venom of the vermivorous species Conus spurius from the Gulf of Mexico. This conopeptide, initially named Cs68 and later designated κO-SrVIA, is extremely hydrophobic and comprises 31 amino acid residues, including six Cysteines in the framework VI/VII, and a free C-terminus. It inhibits the currents mediated by two human EAG subtypes, Kv10.1 (IC50 = 1.88 ± 1.08 µM) and Kv11.1 (IC50 = 2.44 ± 1.06 µM), and also the human subtype Kv1.6 (IC50 = 3.6 ± 1.04 µM). Despite its clear effects on potassium channels, it shares a high sequence identity with δ-like-AtVIA and δ-TsVIA. Also, κO-SrVIA is the third conopeptide from the venom of C. spurius with effects on potassium channels, and the seventh conotoxin that blocks Kv1.6 channels.

A Novel Dimeric Conotoxin, FrXXA, from the Vermivorous Cone Snail Conus fergusoni, of the Eastern Pacific, Inhibits Nicotinic Acetylcholine Receptors.

We isolated a new dimeric conotoxin with inhibitory activity against neuronal nicotinic acetylcholine receptors. Edman degradation and transcriptomic studies indicate a homodimeric conotoxin composed by two chains of 47 amino acid in length. It has the cysteine framework XX and 10 disulfide bonds. According to conotoxin nomenclature, it has been named as αD-FrXXA. The αD-FrXXA conotoxin inhibited the ACh-induced response on nAChR with a IC50 of 125 nM on hα7, 282 nM on hα3ß2, 607 nM on α4ß2, 351 nM on mouse adult muscle, and 447 nM on mouse fetal muscle. This is first toxin characterized from C. fergusoni and, at the same time, the second αD-conotoxin characterized from a species of the Eastern Pacific.

Ancient and modern genomics of the Ohlone Indigenous population of California.

SignificanceCalifornia supports a high cultural and linguistic diversity of Indigenous peoples. In a partnership of researchers with the Muwekma Ohlone tribe, we studied genomes of eight present-day tribal members and 12 ancient individuals from two archaeological sites in the San Francisco Bay Area, spanning ∼2,000 y. We find that compared to genomes of Indigenous individuals from throughout the Americas, the 12 ancient individuals are most genetically similar to ancient individuals from Southern California, and that despite spanning a large time period, they share distinctive ancestry. This ancestry is also shared with present-day tribal members, providing evidence of genetic continuity between past and present Indigenous individuals in the region, in contrast to some popular reconstructions based on archaeological and linguistic information.

Vigilancia intensificada de enfermedades durante los incendios forestales, Paraguay, 2019

RESUMEN El humo de los incendios forestales puede influir en la mortalidad, las emergencias y las visitas ambulatorias, especialmente en personas con problemas respiratorios y cardiovasculares. La vigilancia intensificada exige sumar recursos adicionales a las actividades rutinarias de vigilancia. En agosto del 2019, se registraron 25.299 focos de incendios en varios departamentos del Paraguay. Se describen los hallazgos de la vigilancia intensificada de enfermedades en la población afectada por incendios forestales en Paraguay en el 2019. Se realizó un estudio descriptivo trasversal entre el 15/08/19 al 4/10/2019 en todo el territorio nacional. Como fuente de datos, se incluyen reportes de las Unidades Epidemiológicas Regionales, organizados en una base de datos con las variables: departamento, distrito, población indígena, número de atenciones médicas, motivo de consulta, heridos graves, desaparecidos y fallecidos, identificación de riesgos potenciales para la salud. Fueron afectados 12 (12/17) departamentos y la Capital del país, 30 distritos y 12 comunidades indígenas. Se realizaron 1.681 atenciones médicas, de los cuales 1.291 (77%) eran de Alto Paraguay. Las enfermedades más frecuentes fueron Infecciones Respiratorias Agudas no neumonías (36%), y Enfermedades Tipo Influenza (18%). No se registraron heridos graves, personas desaparecidas ni fallecidas. Como riesgos potenciales para la salud: pérdidas de viviendas en comunidades indígenas, cultivos, ganados y la interrupción de provisión de agua. En conclusión, los cuadros respiratorios fueron más frecuentes durante los incendios forestales, no se registraron personas desaparecidas ni fallecidas. Se identificaron riesgos potenciales para la salud por afectación de medios de vida y sustento, sobre todo en poblaciones indígenas.

ABSTRACT Smoke from wildfires can influence mortality, emergencies and outpatient visits, especially in people with respiratory and cardiovascular problems. Intensified surveillance requires adding up additional resources to routine surveillance activities. In August 2019, 25,299 fire outbreaks were registered in de various departments Paraguay. The findings of the intensified surveillance of diseases in the population affected by wildfires in Paraguay in 2019 are described. A descriptive cross-sectional study was carried out between 08/15/19 to 10/4/2019 throughout the national territory. As a data source, reports from the Regional Epidemiological Units, organized in a database with the variables: department, district, indigenous populations, number of medical care, reason for consultation, seriously injured, missing and deceased people, identification of potential health risks. Twelve (12/17) departments and the capital of the country, 30 districts and 12 indigenous peoples were affected. One thousand six hundred and eighty-one medical services were performed, of which 1,291 (77%) were from Alto Paraguay. The most frequent diseases were non-pneumonia Acute Respiratory Infections (36%), and Influenza-like illness (18%). There were no injured, missing or dead people. Among the potential health risks: loss of dwellings in indigenous people, crops, livestock and the interruption of water supply. In conclusion, respiratory symptoms were the most frequent during the wildfires, there were no injured, missing or dead people. Potential health risks were identified due to the impact on livelihoods, especially in indigenous populations.

A comparison of proteomic, genomic, and osteological methods of archaeological sex estimation.

Sex estimation of skeletons is fundamental to many archaeological studies. Currently, three approaches are available to estimate sex-osteology, genomics, or proteomics, but little is known about the relative reliability of these methods in applied settings. We present matching osteological, shotgun-genomic, and proteomic data to estimate the sex of 55 individuals, each with an independent radiocarbon date between 2,440 and 100 cal BP, from two ancestral Ohlone sites in Central California. Sex estimation was possible in 100% of this burial sample using proteomics, in 91% using genomics, and in 51% using osteology. Agreement between the methods was high, however conflicts did occur. Genomic sex estimates were 100% consistent with proteomic and osteological estimates when DNA reads were above 100,000 total sequences. However, more than half the samples had DNA read numbers below this threshold, producing high rates of conflict with osteological and proteomic data where nine out of twenty conditional DNA sex estimates conflicted with proteomics. While the DNA signal decreased by an order of magnitude in the older burial samples, there was no decrease in proteomic signal. We conclude that proteomics provides an important complement to osteological and shotgun-genomic sex estimation.

A turripeptide from Polystira nobilis venom inhibits human α3ß2 and α7 nicotinic acetylcholine receptors.

Almost all marine snails within superfamily Conoidea produce venoms containing numerous neuroactive peptides. Most toxins characterized from members of this superfamily are produced by species belonging to family Conidae. These toxins (conotoxins) affect diverse membrane proteins, such as voltage- and ligand-gated ion channels, including nicotinic acetylcholine receptors (nAChRs). Family Turridae has been considerably less studied than their Conidae counterpart and, therefore, turrid toxins (turritoxins) have just been barely described. Consequently, in this work the most prominent chromatographic (RP-HPLC) fractions from the East Pacific species Polystira nobilis venom duct extract were isolated. The biological activity of six selected fractions was assayed on human (h) α7 AChRs expressed in Xenopus laevis oocytes. One of these fractions, F21, inhibited the acetylcholine-elicited response by 62 ± 12%. Therefore, this fraction was further purified and the F21-2 peptide was obtained. This peptide (at 5.6 µM) strongly and irreversibly inhibited the acetylcholine-induced response on hα7 and hα3ß2 nAChRs, by 55 ± 4 and 91 ± 1%, respectively. Electrospray mass spectrometry indicates that the average molecular mass of this toxin is 12 358.80 Da. The affinity for hα3ß2 nAChRs is high (IC50 of 566.2 nM). A partial sequence without cysteines was obtained by automated Edman degradation: WFRSFKSYYGHHGSVYRPNEPNFRSFAS…; blastp search revealed that this sequence has low similarity to some non-Cys-containing turripeptides. This is the first report of a turritoxin from a species of the American Pacific and the second description of a turripeptide inhibiting nAChRs.

Oral misoprostol for the management of incomplete abortion in Ecuador.

OBJECTIVE: To assess the feasibility of introducing misoprostol for the treatment of incomplete abortion in Quito, Ecuador. METHODS: In a randomized prospective study conducted at a large tertiary-level maternity hospital and a private secondary-level clinic between November 2006 and November 2007, women with incomplete abortion were treated with either 600 µg of oral misoprostol (n=122) or manual vacuum aspiration (MVA) (n=120). All participants were requested to return for follow-up care on day 7 to determine the success of the treatment and to document their satisfaction with the method and the adverse effects experienced. RESULTS: Sixteen percent of women (39/242) did not return for their follow-up visit and their outcomes are unknown. Among those who did return, 94% (100/106) of women showed successful completion of abortion after treatment with misoprostol, as compared with 100% (97/97) of women treated with MVA. Most women described their adverse effects after treatment as tolerable (misoprostol, 95%; MVA, 91%). Nearly all women reported being satisfied with their treatment (196/203); there were no differences among the women's reports of satisfaction according to treatment received. CONCLUSION: An oral dose of 600 µg of misoprostol was found to be an acceptable and effective non-surgical option for treating incomplete abortion. Clinical trials.gov NCT00674232.