The maternal reward system in postpartum depression

Archives of Women's Mental Health - The experience of motherhood is most often emotionally positive and rewarding, but for many new mothers suffering from postpartum depression (PPD), this is...     

Food Hardship and Obesity in a Sample of Low-Income Immigrants

Very little work has examined the relationship between food hardship (having inconsistent financial resources to buy food) and obesity among immigrant groups. A cross-sectional study was conducted in a low-income, multi-racial/ethnic adult sample in greater Boston, MA (n = 828). Modified Poisson regression models estimated the association between food hardship obesity (BMI ≥ 30) among adults reporting food hardship; interactions were tested by place of birth. Body mass index (BMI) was based on anthropometric height and weight. In adjusted models, those experiencing food hardship were more likely to be obese (RR 1.17, CI 1.07, 1.29) than those not experiencing food hardship. Participants from Haiti reporting food hardship were more likely to be obese than those not reporting hardship (RR 1.58, CI 1.23, 2.04); this was not the case among other groups (US born, Puerto Rican, Latin American, Other). The relationship between food hardship and weight may vary among immigrant subgroups.     

De novo SDHB gene mutation in a family with extra-adrenal paraganglioma

Familial Cancer - A 14-year-old male presented with abdominal pain. Imaging illustrated a left-sided adrenal mass; he underwent a left nephrectomy, confirming an extra-adrenal PGL. Germline genetic...     

Roadmap for the international collaborative epidemiologic monitoring of safety and effectiveness of new high priority vaccines

With the advent of new vaccines targeted to highly endemic diseases in low- and middle-income countries (LMIC) and with the expansion of vaccine manufacturing globally, there is an urgent need to establish an infrastructure to evaluate the benefit-risk profiles of vaccines in LMIC. Fortunately the usual decade(s)-long time gap between introduction of new vaccines in high and low income countries is being significantly reduced or eliminated due to initiatives such as the Global Alliance for Vaccines and Immunizations (GAVI) and the Decade of Vaccines for the implementation of the Global Vaccine Action Plan. While hoping for more rapid disease control, this time shift may potentially add risk, unless appropriate capacity for reliable and timely evaluation of vaccine benefit-risk profiles in some LMIC's are developed with external assistance from regional or global level. An ideal vaccine safety and effectiveness monitoring system should be flexible and sustainable, able to quickly detect possible vaccine-associated events, distinguish them from programmatic errors, reliably and quickly evaluate the suspected event and its association with vaccination and, if associated, determine the benefit-risk of vaccines to inform appropriate action. Based upon the demonstrated feasibility of active surveillance in LMIC as shown by the Burkina Faso assessment of meningococcal A conjugate vaccine or that of rotavirus vaccine in Mexico and Brazil, and upon the proof of concept international GBS study, we suggest a sustainable, flexible, affordable and timely international collaborative vaccine safety monitoring approach for vaccines being newly introduced. While this paper discusses only the vaccine component, the same system could also be eventually used for monitoring drug effectiveness (including the use of substandard drugs) and drug safety.     

Community-Level Cardiovascular Risk Factors Impact Geographic Variation in Cardiovascular Disease Hospitalizations for Women

Prior work has shown significant geographic variation in cardiovascular (CV) risk factors including metabolic syndrome, obesity, and hypercholesterolemia. However, little is known about how variations in CV risk impact cardiovascular disease (CVD)-related hospitalizations. Community-level CV risk factors (hypertension, dyslipidemia, hyperglycemia, and elevated waist circumference) were assessed from community-wide health screenings sponsored by Sister to Sister (STS) from 2008 to 2009 in 17 major US cities. Using data from the Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample (HCUP-NIS), CVD hospitalizations were identified based on ICD-9 codes for acute myocardial infarction (AMI), congestive heart failure (CHF), and stroke. We linked STS data with HCUP-NIS hospitalizations based on common cities and restricted the analysis to women discharged from hospitals inside the STS cities. Using hierarchical models with city as the random intercept, we assessed the impact of city-specific CV risk factors on between-city variance of AMI, CHF, and stroke. Analyses were also adjusted for patient age and clinical comorbidities. Our analysis yielded a total of 742,445 all-cause discharges across 70 hospitals inside of 13 linked cities. The overall city-specific range proportion of AMI, CHF, and stroke hospitalizations were 1.13 % (0.75–1.59 %), 2.57 % (1.44–3.92 %), and 1.24 % (0.66–1.84 %), respectively. After adjusting for city-specific CV risk factors, between-city variation was no longer statistically significant for all CVD conditions explored. In conclusion, we found that geographic variations in AMI, CHF, and stroke hospitalizations for women may be partially explained by community-level CV risk factors. This finding suggests that interventions to reduce CVD should be tailored to the unique risk profile and needs of high-risk communities.     

Mutational Analysis of Quinolone Resistance Protein QnrB1

Alanine substitutions and selected deletions have been used to localize amino acids in QnrB essential for its protective activity. Essential amino acids are found at positions i and i⁻² in the pentapeptide repeat module and in the larger of two loops, where deletion of only a single amino acid compromises activity. Deletion of 10 amino acids at the N terminus is tolerated, but removal of 3 amino acids in the C-terminal dimerization unit destroys activity.     

Enhancing memory of stair height by the motor experience of stepping

A concept emerging from recent studies on obstacle avoidance in quadrupeds is that working memory of the height of an obstacle established by visual information is enhanced by motor interactions with the obstacle. In this investigation, we found that this concept is valid in adult humans when viewing and walking up stairs. The main finding was that the memory of the height of stairs was enhanced when information about stair height was gained by walking up a short flight of stairs compared to when information about stair height was gained by vision alone. By measuring the maximum toe clearance when subjects step onto a stair, we observed that maximum toe clearance increased after diverting vision from the stair for a few seconds prior to stepping. Most of this increase occurred within a 2-s period between diverting vision from the stair and initiating the step. By contrast, this increase in maximum toe clearance after diverting vision from a stair was significantly reduced after subjects walked up two stairs prior to stepping onto a stair without vision. This reduction persisted for delays as long as 10?s between diverting vision from the stair and initiating the step. In four of twelve subjects, the maximum toe clearance after these long periods without vision of the stair was close to the value when steps were made with full vision of the stairs.     

Diverse high-torque bacterial flagellar motors assemble wider stator rings using a conserved protein scaffold

Although it is known that diverse bacterial flagellar motors produce different torques, the mechanism underlying torque variation is unknown. To understand this difference better, we combined genetic analyses with electron cryo-tomography subtomogram averaging to determine in situ structures of flagellar motors that produce different torques, from Campylobacter and Vibrio species. For the first time, to our knowledge, our results unambiguously locate the torque-generating stator complexes and show that diverse high-torque motors use variants of an ancestrally related family of structures to scaffold incorporation of additional stator complexes at wider radii from the axial driveshaft than in the model enteric motor. We identify the protein components of these additional scaffold structures and elucidate their sequential assembly, demonstrating that they are required for stator-complex incorporation. These proteins are widespread, suggesting that different bacteria have tailored torques to specific environments by scaffolding alternative stator placement and number. Our results quantitatively account for different motor torques, complete the assignment of the locations of the major flagellar components, and provide crucial constraints for understanding mechanisms of torque generation and the evolution of multiprotein complexes.Flagellated bacteria have tailored their motility to diverse habitats. For example, the enteric model organisms Salmonella enterica serovar Typhimurium and Escherichia coli colonize animal digestive tracts and can reside outside a host, assembling flagella over their cell body to swim. However, a diverse spectrum of flagellar swimming ability is seen across the bacterial kingdom. Caulobacter crescentus inhabits low-nutrient freshwater environments where it swims using a high-efficiency flagellar motor (1, 2), whereas Vibrio species produce high-speed, sodium-driven polar flagella to capitalize on the high sodium gradient of their marine habitat (3). On the other hand, the ε-proteobacteria and spirochetes, many of which thrive exclusively in association with a host, have evolved characteristically rapid and powerful swimming capabilities that enable them to bore through mucous layers coating epithelial cells or between tissues. Indeed, the ε-proteobacteria Campylobacter jejuni and Helicobacter pylori are capable of continued swimming in high-viscosity media that immobilize E. coli or Vibrio cells (4–6), and similar behavior is observed for spirochetes (7, 8).Despite differences in the organisms’ swimming ability, the flagellar motor is composed of a conserved core of ∼20 structural proteins (9). The mechanism of flagellar motility is conserved (10), with torque generated by rotor and stator components (9). Stator complexes, heterooligomers of four motility A (MotA) and two motility B (MotB) proteins, are thought to form a ring that surrounds the axial driveshaft. Transmembrane helices of MotA and MotB form an ion channel, and MotB features a large periplasmic domain that binds peptidoglycan (11, 12) and the flagellar structural component, the P-ring (13). The stator complex couples ion flux to exertion of force on the cytoplasmic rotor ring (the C-ring), which transmits torque to the axial driveshaft (the rod), universal joint (the hook), and helical propeller (the filament), culminating in propulsion of the bacterium. Biophysical (14) and freeze-fracture (15) studies together with modeling (16) have proposed that a tight ring of ∼11 stator complexes dynamically assembles around the rod above the outer lobe of the C-ring in closely related Salmonella and E. coli motors (which we collectively refer to as the “enteric motor”). However, despite these conclusions, and although the structures observed in subtomogram averages have been proposed to be the stator complexes (17–19), the locations and stoichiometries of the stator complexes remain to be confirmed.How can we explain the wide diversity in flagellar swimming abilities in the context of a conserved core flagellar motor? Biophysical studies suggest that the source of the difference lies, at least in part, in variations in the mechanical output of the motors themselves. Torques of motors from different bacteria have been shown to range over an order of magnitude, and torque correlates with swimming speed and the ability of bacteria to propel themselves through different viscosities, indicating that adaptations are likely to be at the level of the motor itself. [Torque also varies within a single species, up to a maximum value, as a function of the number of stator complexes incorporated into the motor (14)]. For example, C. crescentus motors have been measured to produce torques of 350 pN⋅nm (2). Estimates for the torque of the enteric motor ranges from ∼1,300 to ∼2,000 pN⋅nm (20, 21). The ε-proteobacterium H. pylori has been estimated to swim with torque of 3,600 pN⋅nm (22), and spirochetes are capable of swimming with 4,000 pN⋅nm of torque (21, 23). Sodium-driven motor torques in Vibrio spp. have been measured between ∼2,000 and 4,000 pN⋅nm (24), depending on the magnitude of the sodium gradient. It is noteworthy, however, that an estimated sodium motive force in Vibrio spp. that is lower than the standard E. coli proton motive force nevertheless drives the Vibrio motor with higher torque than the E. coli motor (24, 25), further suggesting that torque differences likely exist at the level of the motor. However, the molecular mechanism by which different motors might produce different torques has not been investigated.The simplest scenario for tuning motor torque would be evolved adaptation of motor architecture. In support of this scenario, we recently showed that many motors have evolved additional structures not found in the well-studied enteric motors (18), and we observed that the C-ring radius varies among species (17, 18). One of the most widespread novel structures is a periplasmic basal disk directly beneath the outer membrane, often co-occurring with varied uncharacterized additional structures, which we collectively term “disk complexes.” Consistently, disk complexes have been seen only in motors that produce torque higher than that in E. coli or Salmonella. For example, the sodium-driven ∼2,000+ pN⋅nm torque motors of Vibrio species assemble a disk complex featuring a basal disk beneath the outer membrane (18) in addition to smaller H- and T-rings composed of FlgOT (flagella O, T) and MotXY (motility X, Y), respectively (26, 27). It has been shown that the T-ring interacts with stator complexes in Vibrio spp. (28), although the exact location and number of stator complexes in Vibrio spp. remains unclear. ε-Proteobacteria such as Helicobacter species, C. jejuni, and Wolinella succinogenes also assemble disk complexes composed of large basal disks beneath the outer membrane together with additional smaller disks (18, 29). Although these and other cases of additional disks have been reported (18, 30), their relation to flagellar function remains enigmatic, and it is unclear if these widespread disk complexes are homologous or analogous.In this study, we hypothesized that bacteria have tuned their swimming abilities by evolving structural adaptations to their flagellar motors that would result in altered torque generation. Using electron cryo-tomography and subtomogram averaging, we found that Vibrio polar γ-proteobacterial and Campylobacter ε-proteobacterial flagellar motors incorporate 13 and 17 stator complexes, respectively, compared with the ∼11 in enteric bacteria. In both cases, these stator complexes are scaffolded into wider stator rings relative to the enteric motor by components of their respective disk complexes. The wider C. jejuni stator ring is further reflected in a considerably wider rotor C-ring. Further analysis of the components of the Vibrio and C. jejuni disk complexes reveals that they share a core protein, FlgP, but each has acquired diverse additional components to form divergent disk-complex architectures. We conclude by showing that our structural data of wider stator rings featuring additional stator complexes can quantitatively account for the differences in torque between different flagellar motors.