Political Determinants of Population Health: The case of Donald Trump’s election, Trump’s campaign rallies and U.S. states’ prioritization of carceral spending

Between 80% and 90% of the modifiable contributors to population health are social determinants of health: health-related behaviors, socio-economic factors, and environmental factors, in other words, the conditions in which people are born, grow, live, work and age. (Hood et al. 2016; Magnan 2017). These circumstances are, at least in part, political constructions (Rodriguez 2019). At the macro-level, political factors include the character, ideology, and policies of political regimes and governing political parties (Beckfield and Krieger 2009; Rodriguez 2019; Torche and Rauf 2021). Yet even in the absence of policy implementation, politics influences health (Brown, Solazzo, and Gorman 2021; Gemmill et al. 2019; Lauderdale 2006; Morey et al. 2021; Samari et al. 2020; Torche and Sirois 2019). In this dissertation I study the link between three political determinants of population health in the U.S. and infant health and mortality: Donald Trump’s election in November 2016, Trump’s 2015-2016 presidential campaign rallies, and U.S. states’ prioritization of carceral spending from 1980-2008. In the first dissertation chapter, I investigate whether rates of and disparities in adverse birth outcomes between racialized and nativity groups changed after Donald Trump’s November 2016 election, a period characterized by an increase in xenophobic and racist messages, policies, and actions in the U.S. Using data from 15,568,710 U.S. births between November 2012 and November 2018, we find that adverse birth outcomes increased after Trump’s election among U.S.- and foreign-born mothers racialized as Black, Hispanic, and Asian & Pacific Islander, compared to the period encompassing the two Obama presidencies. Results for Whites suggest no change or a slight decrease in adverse outcomes following Trump’s election, yet this finding was not robust to checks for seasonality. Black-White, Hispanic-White, and API-White disparities in adverse birth outcomes widened among both U.S.- and foreign-born mothers after Trump’s election. Findings suggest that Trump’s election was a racist and xenophobic macro-level political. In the second dissertation chapter, I provide estimates for the causal effect of Donald Trump’s presidential campaign rallies on infant health by using a staggered difference-in-difference research design using data of geocoded Trump rallies linked to monthly, county-level data from U.S. birth records collected between June 2014 and November 2017. I find that Trump rallies led to increases in very low birthweight among infants born to foreign-born Hispanic birthing parents and in low birthweight among infants born to foreign-born Asian and Pacific Islander birthing parents. This effect was not observed among U.S.-born women or foreign-born White and Black women. These ethnicity and race-specific health effects suggest that Trump's presidential rallies constituted a significant stressor for Hispanic and API foreign-born groups residing in the U.S. Further, this study underscores a significant finding: political events, and not just policy changes, have adverse effects on human health. In the third dissertation chapter, I examine the association between a state prioritization of carceral spending over welfare expenditure and Black and White death rates in 42 U.S. states between 1980 and 2008. Using fixed-effects models and controlling for confounders, I find that U.S. states’ fiscal prioritization of carceral systems to the exclusion of health and support is associated with an increased number of both Black and White deaths. The association between a states’ carceral prioritization and Black death is larger than its association with White death, meaning that penal states increase racial inequality in mortality. Further, these negative consequences are concentrated in the South for both groups and in the West for White groups. My findings suggest that a penal-welfare regime that prioritizes punitive control over welfare support is a racializing tool used by U.S. states harms population health and disproportionately harms the health of Black groups living in the South

DACA Associated with Improved Birth Outcomes Among Mexican-Immigrant Mothers

The 2012 Deferred Action for Childhood Arrivals (DACA) program granted work authorization and protection from deportation to more than 800,000 young undocumented immigrants who arrived to the United States as minors. In a recent study, we investigated the association between this expansion of legal rights and birth outcomes among 72,613 singleton births to high school-educated Mexican-immigrant women in the United States from June 2010 to May 2014 using birth records data from the National Center for Health Statistics. We found that DACA was associated with improvements in the rates of low birth weight and very low birth weight, birth weight in grams, and gestational age among infants born to Mexican-immigrant mothers. Policymakers should consider this evidence of DACA's direct and intergenerational health benefits in future reforms of immigration legislation

Enhanced perioperative care in emergency general surgery:the WSES position paper

Enhanced perioperative care protocols become the standard of care in elective surgery with a significant improvement in patients' outcome. The key element of the enhanced perioperative care protocol is the multimodal and interdisciplinary approach targeted to the patient, focused on a holistic approach to reduce surgical stress and improve perioperative recovery. Enhanced perioperative care in emergency general surgery is still a debated topic with little evidence available. The present position paper illustrates the existing evidence about perioperative care in emergency surgery patients with a focus on each perioperative intervention in the preoperative, intraoperative and postoperative phase. For each item was proposed and approved a statement by the WSES collaborative group.</p

Whole-Exome Sequencing Identifies Homozygous AFG3L2 Mutations in a Spastic Ataxia-Neuropathy Syndrome Linked to Mitochondrial m-AAA Proteases

We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Whole-exome sequencing identified a homozygous missense mutation (c.1847G>A; p.Y616C) in AFG3L2, encoding a subunit of an m-AAA protease. m-AAA proteases reside in the mitochondrial inner membrane and are responsible for removal of damaged or misfolded proteins and proteolytic activation of essential mitochondrial proteins. AFG3L2 forms either a homo-oligomeric isoenzyme or a hetero-oligomeric complex with paraplegin, a homologous protein mutated in hereditary spastic paraplegia type 7 (SPG7). Heterozygous loss-of-function mutations in AFG3L2 cause autosomal-dominant spinocerebellar ataxia type 28 (SCA28), a disorder whose phenotype is strikingly different from that of our patients. As defined in yeast complementation assays, the AFG3L2Y616C gene product is a hypomorphic variant that exhibited oligomerization defects in yeast as well as in patient fibroblasts. Specifically, the formation of AFG3L2Y616C complexes was impaired, both with itself and to a greater extent with paraplegin. This produced an early-onset clinical syndrome that combines the severe phenotypes of SPG7 and SCA28, in additional to other “mitochondrial” features such as oculomotor apraxia, extrapyramidal dysfunction, and myoclonic epilepsy. These findings expand the phenotype associated with AFG3L2 mutations and suggest that AFG3L2-related disease should be considered in the differential diagnosis of spastic ataxias

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Loss of Prohibitin Membrane Scaffolds Impairs Mitochondrial Architecture and Leads to Tau Hyperphosphorylation and Neurodegeneration

Fusion and fission of mitochondria maintain the functional integrity of mitochondria and protect against neurodegeneration, but how mitochondrial dysfunctions trigger neuronal loss remains ill-defined. Prohibitins form large ring complexes in the inner membrane that are composed of PHB1 and PHB2 subunits and are thought to function as membrane scaffolds. In Caenorhabditis elegans, prohibitin genes affect aging by moderating fat metabolism and energy production. Knockdown experiments in mammalian cells link the function of prohibitins to membrane fusion, as they were found to stabilize the dynamin-like GTPase OPA1 (optic atrophy 1), which mediates mitochondrial inner membrane fusion and cristae morphogenesis. Mutations in OPA1 are associated with dominant optic atrophy characterized by the progressive loss of retinal ganglion cells, highlighting the importance of OPA1 function in neurons. Here, we show that neuron-specific inactivation of Phb2 in the mouse forebrain causes extensive neurodegeneration associated with behavioral impairments and cognitive deficiencies. We observe early onset tau hyperphosphorylation and filament formation in the hippocampus, demonstrating a direct link between mitochondrial defects and tau pathology. Loss of PHB2 impairs the stability of OPA1, affects mitochondrial ultrastructure, and induces the perinuclear clustering of mitochondria in hippocampal neurons. A destabilization of the mitochondrial genome and respiratory deficiencies manifest in aged neurons only, while the appearance of mitochondrial morphology defects correlates with tau hyperphosphorylation in the absence of PHB2. These results establish an essential role of prohibitin complexes for neuronal survival in vivo and demonstrate that OPA1 stability, mitochondrial fusion, and the maintenance of the mitochondrial genome in neurons depend on these scaffolding proteins. Moreover, our findings establish prohibitin-deficient mice as a novel genetic model for tau pathologies caused by a dysfunction of mitochondria and raise the possibility that tau pathologies are associated with other neurodegenerative disorders caused by deficiencies in mitochondrial dynamics

<i>CaMKIIa-Cre</i>-mediated inactivation of the mouse <i>Phb2</i> gene in forebrain neurons.

<p>(A) <i>In-situ</i> hybridization of <i>Phb2</i> mRNA in the hippocampus of 8-week-old <i>Phb2^NKO</i> and <i>Phb2^fl/fl</i> control mice. Scale bar: 500 µm. (B) Immunoblot analysis of tissue lysates generated from the indicated brain regions of <i>Phb2^NKO</i> (KO) and <i>Phb2^fl/fl</i> (WT) control mice of different age using PHB1- and PHB2-specific antibodies. Ponceau S (PoS) staining was used to monitor equal gel loading. Cortex (CO), striatum (ST), hippocampus (HC), cerebellum (CB). (C) Representative photographs of 20-week-old <i>Phb2^NKO</i> mice of the indicated genotypes showing lordokyphosis (left panel) and excessive pathological grooming (right panel). White arrows indicate regions of self-inflicted open skin lesions. (D) Body weight analysis of <i>Phb2^NKO</i> and <i>Phb2^fl/fl</i> control animals. n = 20. ***<i>P</i><0.001. Error bars indicate SEM. (E) Kaplan-Meier survival plot of <i>Phb2^NKO</i> (n = 30) and control animals (<i>Phb2^fl/fl</i> (n = 59), <i>Phb2^HET</i> (n = 19)). <i>P</i><0.0001.</p

Defective mitochondrial morphogenesis and ultrastructure in <i>Phb2</i>-deficient neurons <i>in vivo</i>.

<p>(A) Transmission electron microscopy analysis of the mitochondrial ultrastructure in DG neurons of 6-week-old <i>Phb2^NKO</i> and <i>Phb2^fl/fl</i> control mice. The enlargements show the double membrane of the mitochondrion and the emergence of one crista. Scale bar: 400 nm. (B) Fragmentation and perinuclear clustering of PHB2-deficient neuronal mitochondria. Primary hippocampal neurons isolated from E18.5 <i>Phb2^fl/fl</i> embryos were infected with lentiviruses expressing mitochondrially targeted EGFP and Cre recombinase (NLS-Cre) as indicated. Fixed samples were immunostained with antibodies directed against GFP and neuronal <i>β</i>III-tubulin followed by DAPI staining. a′, b′ are magnifications of the boxed insets shown in a, b. Scale bars: 10 µm. (C) Quantification of mitochondrial morphology in PHB2-deficient and control primary hippocampal neurons. Cells were infected with lentiviruses expressing Cre recombinase when indicated and processed as described in (B). Cells containing tubular (white bars) or fragmented mitochondria (red bars) were classified. >200 cells were scored in three independent experiments. ***<i>P</i><0.001. Error bars indicate SEM. (D) Quantification of mitochondria per neurites in PHB2-deficient primary hippocampal neurons. <i>Phb2^fl/fl</i> neurons were infected with lentiviruses expressing Cre recombinase when indicated and processed as described in (B). >30 cells were scored in three independent experiments. **<i>P</i><0.01. Error bars indicate SEM. (E) Immunoblot analysis of hippocampal tissue lysates from <i>Phb2^NKO</i> (KO) and <i>Phb2^fl/fl</i> (WT) control mice of the indicated age. Lysates were analyzed by SDS-PAGE and immunoblotting using the indicated antibodies. Antibodies directed against VDAC and the 70 kDa subunit of complex II were used to monitor equal gel loading. b/e: long/short OPA1 isoforms.</p