Glutaredoxin proteins from E. coli isoforms were compared in terms of energy frustration.

Glutaredoxin (GRXs) protein plays a vital role inside the cell, including redox control of transcription to the cell's antioxidant defense, apoptosis, and cellular differentiation regulation. In this study, we have investigated the energy landscape and characterized the pattern of local frustration in different forms and states of the GRX protein ofE. coli.Analysis was done on the conformational alterations, significant changes in the frustration pattern, and different GRXs such as GRX-II, GRX-III, GRX-II-GSH, and GRX-III-GSH complex. We have found the practice of frustration, and structure was quite similar in the same isoform having different states of protein; however, a significant difference was observed between different isoforms. Moreover, oxidation of GRX-I introduced an extra α-helix increasing the destabilizing interactions within the protein. The study of frustrated contacts on oxidized and reduced GRX and with bound and unbound Glutathione indicates its potential application in activating and regulating the behavior of GRXs.

Metal nanoparticles produced by plants with antibacterial properties against Staphylococcus aureus.

Staphylococcus aureus (S. aureus) is a pathogenic bacteria that causes a variety of potentially fatal infections. The emergence of antibiotic-resistant strains of S. aureus has made treatment even more difficult. In recent years, nanoparticles have been used as an alternative therapeutic agent for S. aureus infections. Among various methods for the synthesis of nanoparticles, the method utilizing plant extracts from different parts of a plant, such as root, stem, leaf, flower, seeds, etc. is gaining widespread usage. Phytochemicals present in plant extract are an inexpensive, eco-friendly, natural material that act as reducing and stabilization agent for the nanoparticle synthesis. The utilization of plant-fabricated nanoparticles against S. aureus is currently in trend. The current review discusses recent findings in the therapeutic application of phytofabricated metal-based nanoparticles against Staphylococcus aureus.

Glutaredoxin proteins from E. coli isoforms were compared in terms of energy frustration / Proteínas glutaredoxinas de isoformas de E. coli foram comparadas em termos de frustração de energia

Abstract Glutaredoxin (GRXs) protein plays a vital role inside the cell, including redox control of transcription to the cell's antioxidant defense, apoptosis, and cellular differentiation regulation. In this study, we have investigated the energy landscape and characterized the pattern of local frustration in different forms and states of the GRX protein ofE. coli.Analysis was done on the conformational alterations, significant changes in the frustration pattern, and different GRXs such as GRX-II, GRX-III, GRX-II-GSH, and GRX-III-GSH complex. We have found the practice of frustration, and structure was quite similar in the same isoform having different states of protein; however, a significant difference was observed between different isoforms. Moreover, oxidation of GRX-I introduced an extra α-helix increasing the destabilizing interactions within the protein. The study of frustrated contacts on oxidized and reduced GRX and with bound and unbound Glutathione indicates its potential application in activating and regulating the behavior of GRXs.

Resumo A proteína glutaredoxina (GRXs) desempenha um papel vital dentro da célula, incluindo o controle redox da transcrição para a defesa antioxidante da célula, apoptose e regulação da diferenciação celular. Neste estudo, investigamos a paisagem energética e caracterizamos o padrão de frustração local em diferentes formas e estados da proteína GRX de E. coli. A análise feita foi sobre as alterações conformacionais, mudanças significativas no padrão de frustração e diferentes GRXs, como GRX-II, GRX-III, GRX-II-GSH e complexo GRX-III-GSH. Encontramos a prática da frustração, e a estrutura era bastante semelhante na mesma isoforma com diferentes estados de proteína; no entanto, uma diferença significativa foi observada entre diferentes isoformas. Além disso, a oxidação de GRX-I introduziu uma α-hélice extra, aumentando as interações desestabilizadoras dentro da proteína. O estudo de contatos frustrados em GRX oxidado e reduzido e com glutationa ligada e não ligada indica sua potencial aplicação na ativação e regulação do comportamento de GRXs.

Health care in pregnancy during the COVID-19 pandemic and pregnancy outcomes in six low- and-middle-income countries: Evidence from a prospective, observational registry of the Global Network for Women's and Children's Health

Objective: To assess, on a population basis, the medical care for pregnant women in specific geographic regions of six countries before and during the first year of the coronavirus disease 2019 (COVID-19) pandemic in relationship to pregnancy outcom. Results: Across all sites, a small but statistically significant increase in home births occurred between the pre-COVID-19 and COVID-19 periods (18.9% versus 20.3%, adjusted relative risk [aRR] 1.12, 95% CI 1.05­1.19). A small but significant decrease in the mean number of antenatal care visits (from 4.1 to 4.0, p = <0.0001) was seen during the COVID-19 period. Of outcomes evaluated, overall, a small but significant decrease in low-birthweight infants in the COVID-19 period occurred (15.7% versus 14.6%, aRR 0.94, 95% CI 0.89­0.99), but we did not observe any significant differences in other outcomes. There was no change observed in maternal mortality or antenatal haemorrhage overall or at any of the sites. Conclusions: Small but significant increases in home births and decreases in the antenatal care services were observed during the initial COVID-19 period; however, there was not an increase in the stillbirth, neonatal mortality, maternal mortality, low birthweight, or preterm birth rates during the COVID-19 period compared with the previous year. Further research should help to elucidate the relationship between access to and use of pregnancy-related medical services and birth outcomes over an extended period

A tetra-nuclear nickel(II) complex, [Ni4(L)4](ClO4)4·C2H3N·2H2O, with an asymmetric Ni4O4 open-cubane-like core.

A tetra-nuclear complex with an open-cubane-like core structure was synthesized from 2-meth-oxy-6-(pyridin-2-yl-hydrazonometh-yl)phenol (HL), namely, cyclo-tetra-kis-(µ-2-meth-oxy-6-{[2-(pyridin-2-yl)hydrazin-1-yl-idene]meth-yl}pheno-lato)tetra-nickel(II) tetra-kis-(perchlorate) aceto-nitrile monosolvate dihydrate, [Ni4(C13H12N3O2)4](ClO4)4·C2H3N·2H2O, and characterized using micro-analytical and spectroscopic techniques. The crystal-structure determination reveals the formation of a distorted Ni4O4 cubane-like core architecture encapsulated by four hydrazone Schiff base (HL) mol-ecules. A open-cube tetra-nuclear architecture is created in which nickel(II) ions of the NiN2O3 unit are connected by µ2-O anions of the phenolate moiety of HL. In this complex, each Ni centre has a slightly distorted square-pyramidal coordination environment. The supra-molecular architectures are stabilized via the presence of various inter-molecular hydrogen bonds and (ar-yl-aryl, ar-yl-chelate and chelate-chelate) stacking inter-actions.

Knowledge, attitude and practices of pregnant women related to COVID-19 infection: A cross-sectional survey in seven countries from the Global Network for Women's and Children's Health

Objective. We sought to understand knowledge, attitudes and practices (KAP) regarding COVID-19 in pregnant women in seven low and middle-income countries (LMIC). Results. In all, 25 260 women completed the survey. Overall, 56.8% of women named ≥3 COVID-19 symptoms, 34.3% knew ≥2 transmission modes, 51.3% knew ≥3 preventive measures and 79.7% named at least one high-risk condition. Due to COVID-19 exposure concerns, 23.8% had avoided prenatal care and 7.5% planned to avoid hospital delivery. Over half the women in the Guatemalan site and 40% in the Pakistan site reduced care seeking due to COVID-19 exposure concerns. Of the women, 24.0% were afraid of getting COVID-19 from healthcare providers. Overall, 63.3% reported wearing a mask and 29.1% planned to stay at home to reduce COVID-19 exposure risk

Metal nanoparticles produced by plants with antibacterial properties against Staphylococcus aureus / Nanopartículas metálicas produzidas por plantas com propriedades antibacterianas contra Staphylococcus aureus

Staphylococcus aureus (S. aureus) is a pathogenic bacteria that causes a variety of potentially fatal infections. The emergence of antibiotic-resistant strains of S. aureus has made treatment even more difficult. In recent years, nanoparticles have been used as an alternative therapeutic agent for S. aureus infections. Among various methods for the synthesis of nanoparticles, the method utilizing plant extracts from different parts of a plant, such as root, stem, leaf, flower, seeds, etc. is gaining widespread usage. Phytochemicals present in plant extract are an inexpensive, eco-friendly, natural material that act as reducing and stabilization agent for the nanoparticle synthesis. The utilization of plant-fabricated nanoparticles against S. aureus is currently in trend. The current review discusses recent findings in the therapeutic application of phytofabricated metal-based nanoparticles against Staphylococcus aureus.

Staphylococcus aureus (S. aureus) é uma bactéria patogênica que causa uma variedade de infecções potencialmente fatais. O surgimento de cepas de S. aureus resistentes a antibióticos tornou o tratamento ainda mais difícil. Nos últimos anos, as nanopartículas têm sido utilizadas como um agente terapêutico alternativo para infecções por S. aureus. Entre os diversos métodos para a síntese de nanopartículas, o que utiliza extratos vegetais de diferentes partes de uma planta, como raiz, caule, folha, flor, sementes etc., vem se destacando a partir do uso generalizado. Os fitoquímicos presentes no extrato vegetal são um material natural de baixo preço e ecologicamente correto que atuam como agente redutor e estabilizador para a síntese de nanopartículas. A utilização de nanopartículas fabricadas em plantas contra S. aureus é uma tendência atualmente. Nesse sentido, presente trabalho discute achados recentes na aplicação terapêutica de nanopartículas à base de metal fitofabricadas contra Staphylococcus aureus.

Early outcomes after definitive chemoradiation therapy with Vienna/Venezia hybrid high-dose rate brachytherapy applicators for cervical cancer: A single-institution experience.

PURPOSE: The Vienna and Venezia (Elekta) are hybrid intracavitary/interstitial brachytherapy (BT) applicators for cervical cancers unsuitable for intracavitary BT alone to improve target coverage or reduce critical organ dose. There is limited outcome data with the use of these applicators outside published experience of the EMBRACE group. We report feasibility and early outcomes with the use of these hybrid applicators at our institution. METHODS AND MATERIALS: Hybrid applicators were used to treat 61 patients with cervical cancer from November 2011 to December 2019. Indications for hybrid applicator use were involvement of the vagina in 10 patients (16%), residual central or parametrial disease in 46 patients (75%), and a narrow introitus in 5 patients (9%). Toxicities were graded using the CTCAE v4.0. Outcomes were assessed with the Kaplan-Meier method. RESULTS: Median follow-up was 16 months (IQR 9-32 mos). Median HRCTV volume was 31.6 cm3 (IQR 25-48 cm3). Median HRCTV D90 was 86.1 Gy (IQR 84.3-88.0 Gy). In 54 patients with follow-up PET/CT at 3 months, complete initial imaging response locally was seen in 46 patients.Estimated 12-month Kaplan-Meier overall survival, locoregional control, distant control, and recurrence-free survival estimates were 86.9%, 80.6%, 73.8%, and 65.9%, respectively. The 12-month incidence of Grade 3+ GI/GU chronic toxicities was 5.7%, consisting of vesicovaginal fistula, rectovaginal fistula, and ureterovesical fistula. CONCLUSIONS: Our single-institution data support the use of the hybrid applicators, as an alternative to traditional BT applicators when clinically warranted. Use of hybrid applicators is feasible with adequate coverage of disease in the vagina and parametrium.

Global Network for Women's and Children's Health Research: probable causes of stillbirth in low- and middle-income countries using a prospectively defined classification system.

OBJECTIVE: We sought to classify causes of stillbirth for six low-middle-income countries using a prospectively defined algorithm. DESIGN: Prospective, observational study. SETTING: Communities in India, Pakistan, Guatemala, Democratic Republic of Congo, Zambia and Kenya. POPULATION: Pregnant women residing in defined study regions. METHODS: Basic data regarding conditions present during pregnancy and delivery were collected. Using these data, a computer-based hierarchal algorithm assigned cause of stillbirth. Causes included birth trauma, congenital anomaly, infection, asphyxia, and preterm birth, based on existing cause of death classifications and included contributing maternal conditions. MAIN OUTCOME MEASURES: Primary cause of stillbirth. RESULTS: Of 109 911 women who were enrolled and delivered (99% of those screened in pregnancy), 2847 had a stillbirth (a rate of 27.2 per 1000 births). Asphyxia was the cause of 46.6% of the stillbirths, followed by infection (20.8%), congenital anomalies (8.4%) and prematurity (6.6%). Among those caused by asphyxia, 38% had prolonged or obstructed labour, 19% antepartum haemorrhage and 18% pre-eclampsia/eclampsia. About two-thirds (67.4%) of the stillbirths did not have signs of maceration. CONCLUSIONS: Our algorithm determined cause of stillbirth from basic data obtained from lay-health providers. The major cause of stillbirth was fetal asphyxia associated with prolonged or obstructed labour, pre-eclampsia and antepartum haemorrhage. In the African sites, infection also was an important contributor to stillbirth. Using this algorithm, we documented cause of stillbirth and its trends to inform public health programs, using consistency, transparency, and comparability across time or regions with minimal burden on the healthcare system. TWEETABLE ABSTRACT: Major causes of stillbirth are asphyxia, pre-eclampsia and haemorrhage. Infections are important in Africa.

A prospective cause of death classification system for maternal deaths in low and middle-income countries: results from the Global Network Maternal Newborn Health Registry.

OBJECTIVE: To describe the causes of maternal death in a population-based cohort in six low- and middle-income countries using a standardised, hierarchical, algorithmic cause of death (COD) methodology. DESIGN: A population-based, prospective observational study. SETTING: Seven sites in six low- to middle-income countries including the Democratic Republic of the Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. POPULATION: All deaths among pregnant women resident in the study sites from 2014 to December 2016. METHODS: For women who died, we used a standardised questionnaire to collect clinical data regarding maternal conditions present during pregnancy and delivery. These data were analysed using a computer-based algorithm to assign cause of maternal death based on the International Classification of Disease-Maternal Mortality system (trauma, termination of pregnancy-related, eclampsia, haemorrhage, pregnancy-related infection and medical conditions). We also compared the COD results to healthcare-provider-assigned maternal COD. MAIN OUTCOME MEASURES: Assigned causes of maternal mortality. RESULTS: Among 158 205 women, there were 221 maternal deaths. The most common algorithm-assigned maternal COD were obstetric haemorrhage (38.6%), pregnancy-related infection (26.4%) and pre-eclampsia/eclampsia (18.2%). Agreement between algorithm-assigned COD and COD assigned by healthcare providers ranged from 75% for haemorrhage to 25% for medical causes coincident to pregnancy. CONCLUSIONS: The major maternal COD in the Global Network sites were haemorrhage, pregnancy-related infection and pre-eclampsia/eclampsia. This system could allow public health programmes in low- and middle-income countries to generate transparent and comparable data for maternal COD across time or regions. TWEETABLE ABSTRACT: An algorithmic system for determining maternal cause of death in low-resource settings is described.

A comprehensive transcriptome of early development in yellowtail kingfish (Seriola lalandi).

Seriola lalandi is an ecologically and economically important species that is globally distributed in temperate and subtropical marine waters. The aim of this study was to identify large numbers of genic single nucleotide polymorphisms (SNPs) and differential gene expression (DGE) related to the early development of normal and deformed S. lalandi larvae using high-throughput RNA-seq data. A de novo assembly of reads generated 40,066 genes ranging from 300 bases to 64,799 bases with an N90 of 788 bases. Homology search and protein signature recognition assigned gene ontology (GO) terms to a total of 15,744 (39.34%) genes. A search against the Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG) retrieved 6808 KEGG orthology (KO) identifiers for 10,520 genes (26.25%), and mapping of KO identifiers generated 337 KEGG pathways. Comparisons of annotated genes revealed that 1262 genes were downregulated and 1047 genes were upregulated in the deformed larvae group compared to the normal group of larvae. Additionally, we identified 6989 high-quality SNPs from the assembled transcriptome. These putative SNPs contain 4415 transitions and 2574 transversions, which will be useful for further ecological studies of S. lalandi. This is the first study to use a global transcriptomic approach in S. lalandi, and the resources generated can be used further for investigation of gene expression of marine teleosts to investigate larval developmental biology. The results of the GO enrichment analysis highlight the crucial role of the extracellular matrix in normal skeleton development, which could be important for future studies of skeletal deformities in S. lalandi and other marine species.

Synthetic chromanol derivatives and their interaction with complex III in mitochondria from bovine, yeast, and Leishmania.

Synthetic chromanol derivatives (TMC4O, 6-hydroxy-2,2,7,8-tetramethyl-chroman-4-one; TMC2O, 6-hydroxy-4,4,7,8-tetramethyl-chroman-2-one; and Twin, 1,3,4,8,9,11-hexamethyl-6,12-methano-12H-dibenzo[d,g][1,3]dioxocin-2,10-diol) share structural elements with the potent inhibitor of the mitochondrial cytochrome (cyt) bc(1) complex stigmatellin. Studies with isolated bovine cyt bc(1) complex demonstrated that these compounds partially inhibit the mammalian enzyme. The aim of this work was to comparatively investigate these toxicological aspects of synthetic vitamin E derivatives in mitochondria of different species. The chromanols and atovaquone as reference compound were evaluated for their inhibition of the cyt bc(1) activity in mitochondrial fractions from bovine hearts, yeast, and Leishmania. In addition, compounds were evaluated in vitro for their inhibitory activity against whole-cell Leishmania and mouse peritoneal macrophages. In these organisms, the chromanols showed a species-selective inhibition of the cyt bc(1) activity different from that of atovaquone. While in atovaquone the side chain mediates species-selectivity, the marked differences for TMC2O and TMC4O in cyt bc(1) inhibition suggests that direct substitution of the chromanol headgroup will control selectivity in these compounds. Low micromolar concentrations of TMC2O (IC(50) = 9.5 ± 0.5 µM) inhibited the growth of Leishmania, and an esterified TMC2CO derivative inhibited the cyt bc(1) activity with an IC(50) of 4.9 ± 0.9 µM. These findings suggest that certain chromanols also exhibit beyond their antioxidative properties antileishmanial activities and that TMC2O derivatives could be useful toward the development of highly active antiprotozoal compounds.

Evaluation of the subaxial injury classification system.

STUDY DESIGN: Retrospective clinical study of patients treated for subaxial cervical spine trauma (SCST) at a tertiary medical center. PURPOSE: Evaluate the validity of the Subaxial Injury Classification (SLIC) system in surgical versus non-surgical decision making for SCST. INCLUSION CRITERIA: Age >12 years, presence of SCST with complete clinical and radiological (CT and MRI) data. EXCLUSION CRITERIA: Patients with incomplete radiographic or clinical data, pathological fractures, isolated upper cervical trauma (occiput to C2), isolated transverse process or spinous process fractures, chronic or age indeterminate fractures, isolate MRI findings, and severe systemic trauma with death prior to either surgical or non-surgical treatment. RESULTS: Fourteen patients were treated non-surgically (C), whereas 24 were treated surgically (S). In the C group, the SLIC score ranged from 0 to 5 points (standard deviation [SD] = 1.20 points; mean 1.07; median 1). Just 1 patient had an SLIC score greater than 2 (7.1% of the patients). In the S group, the SLIC score ranged from 1 to 10 points (standard deviation [SD] = 2.03 points; mean 5.6; median 6). Just 2 patients had an SLIC score smaller than 4 (both with 1 point each, 8.3% of the total group). All the other 22 (accounting for 91.6%) patients had an SLIC of 4 or more points. CONCLUSIONS: Our study suggests that the SLIC classification looks to be a promising system to aid spinal surgeons in the decision-making process of subaxial cervical trauma, but a large prospective cohort study is required.

Outstanding survival and regeneration process by the use of intelligent acellular dermal matrices and mesenchymal stem cells in a burn pig model.

A pig model with a deep large burn was used to study the regeneration process induced by mesenchymal stem cells (MSCs) and acellular pig dermal matrices, made intelligent by the combination with biodegradable nanofibers loaded with growth factors (granulocyte-macrophage colony-stimulating factor and epidermal growth factor) and coated with the anti-CD44 monoclonal antibody (intelligent acellular dermal matrices, IADMs). These IADMs are specially designed to integrate in the wound bed as new biological scaffolds as well as to specifically recruit and attach circulating and/or externally applied MSCs through the anti-CD44 antibody while delivering precise amounts of growth factors. In this way, the reparative process as well as the aesthetic and functional results were enhanced in our burn model. The animal survived, the wound was completely closed, and total regeneration of the skin was obtained without much scarring. Surprisingly, hair follicles and other skin appendages developed despite the severity and deepness of the burn. Even burned muscles and ribs seemed to have undergone a regenerative process by the end of the study. Based on these findings, we have proposed the use of IADMs and autologous, allogeneic or xenogeneic MSCs, as a new paradigm for the future treatment of large burns and probably other dermatological and cosmetic human conditions.

Indications for off pump coronary surgery.

The learning curve in off pump surgery must be followed due to the fact that beating heart coronary surgery is a completely different operation. Beating heart coronary surgery is truly a team approach. Both the surgeon and the anesthesiologist must work in concert to attain a smooth, safe and efficient operation. A sternotomy is performed. All conduits are harvested as for traditional coronary artery bypass grafting (CABG). The pericardium is opened using a "hockey stick" incision. Another incision is made to complete the reflection of the pericardium from the pulmonary artery to the aorta. The heart is then repositioned with the surgeon's hand and exposure device is placed at the apex of the heart. Additional pericardial sutures may place for positioning as needed for exposure to complete the other anastomosis using stabilizers. The left internal mammary artery (LIMA) to left anterior descending artery (LAD) graft is performed first, after the postero-lateral wall or the right side of the heart can be revascularized. After each anastomosis is performed, measurement of the flow through the conduit is recommended. The chest is closed in the standard fashion. Off pump coronary artery grafting has been established as a safe and effective procedure. It involves a totally different mind-set for the surgeon. Indication for off pump coronary surgery depends on the experience and comfort level of the surgeon. Currently, there are a multitude of devices available for both exposure and stabilization to efficiently perform this operation. Therefore, most patients should be considered candidates for off pump coronary revascularization.

Increased cancer mortality following a history of nonmelanoma skin cancer.

CONTEXT: Cancer registries have reported an increased incidence of melanoma and certain noncutaneous cancers following nonmelanoma skin cancer (NMSC). Whether these findings were attributable to intensified surveillance, shared risk factors, or increased cancer susceptibility remains unclear. OBJECTIVE: To determine whether a history of NMSC predicts cancer mortality. DESIGN: Prospective cohort with 12-year mortality follow-up adjusted for multiple risk factors. SETTING: Cancer Prevention Study II, United States and Puerto Rico. PARTICIPANTS: Nearly 1.1 million adult volunteers who completed a baseline questionnaire in 1982. MAIN OUTCOME MEASURE: Deaths due to all cancers and common cancers. RESULTS: After adjusting for age, race, education, smoking, obesity, alcohol use, and other conventional risk factors, a baseline history of NMSC was associated with increased total cancer mortality (men's relative risk [RR], 1.30; 95% confidence interval [CI], 1.23-1.36; women's RR, 1.26; 95% CI, 1.17-1.35). Exclusion of deaths due to melanoma reduced these RRs only slightly. Mortality was increased for the following cancers: melanoma (RR, 3.36 in men, 3.52 in women); pharynx (RR, 2.77 in men, 2.81 in women); lung (RR, 1.37 in men, 1.46 in women); non-Hodgkin lymphoma (RR, 1.32 in men, 1.50 in women); in men only, salivary glands (RR, 2.96), prostate (RR, 1.28), testis (RR, 12.7), urinary bladder (RR, 1.41), and leukemia (RR, 1.37); and in women only, breast (RR, 1.34). All-cause mortality was slightly increased (adjusted men's RR, 1.03 [95% CI, 1.00-1.06]; women's RR, 1.04 [95% CI, 1.00-1.09]). CONCLUSIONS: Persons with a history of NMSC are at increased risk of cancer mortality. Although the biological mechanisms are unknown, a history of NMSC should increase the clinician's alertness for certain noncutaneous cancers as well as melanoma.

Ethnic differences in the growth of lung function in children: a cross-sectional study in inner-city Nottingham.

Measurements of ventilatory capacity have been made in 664 healthy school-children (ages 5-16 years) of European, Afrocaribbean and Indian stock living in the same environment in inner-city Nottingham: 100%, 95% and 80% of these three groups respectively had been born in the UK. The ventilatory capacity data have been analyzed by logarithmic regressions on stature. For forced vital capacity (FVC) and forced expiratory volume (FEV1) a large difference between European and Indian children was found, amounting to 13% at a given stature. The Afrocaribbean children have values similar to those of the Indians. There were no material ethnic differences for peak expiratory flow rate or for FEV1/FVC(%). The differences in FVC and FEV1 appear to be attributable to constitutional rather than environmental influences.