Sibling rivalry between twins in utero and childhood: Evidence from birthweight and survival of 95 919 twin pairs in 72 low- and middle-income countries.

BACKGROUND: This study explores the magnitude and timing of sex and gender disparities in child development by describing differences in health outcomes for male and female siblings, comparing twins to control for all aspects of life circumstances other than sex and gender. METHODS: We construct a repeat cross-sectional dataset of 191 838 twins among 1.7 million births recorded in 214 nationally representative household surveys for 72 countries between 1990 and 2016. To test for biological or social mechanisms that might favor the health of male or female infants, we describe differences in birthweights, attained heights, weights, and survival to distinguish gestational health from care practices after each child is born. RESULTS: We find that male fetuses grow at the expense of their co-twin, significantly reducing their sibling's birthweight and survival probabilities, but only if the other fetus is male. Female fetuses are born significantly heavier when they share the uterus with a male co-twin and have no significant difference in survival probability whether they happen to draw a male or a female co-twin. These findings demonstrate that sex-specific sibling rivalry and male frailty begin in utero, prior to gender bias after birth that typically favors male children. CONCLUSIONS: Sex differences in child health may have competing effects with gender bias that occurs during childhood. Worse health outcomes for males with a male co-twin could be linked to hormone levels or male frailty, and could lead to underestimates of the effect sizes of later gender bias against girls. Gender bias favoring surviving male children may explain the lack of differences in height and weight observed for twins with either male or female co-twins.

Cost and affordability of nutritious diets at retail prices: Evidence from 177 countries.

Many policies and programs aim to bring nutritious diets within reach of the poor. This paper uses retail prices and nutrient composition for 671 foods and beverages to compute the daily cost of essential nutrients required for an active and healthy life in 177 countries around the world. We compare this minimum cost of nutrient adequacy with the subsistence cost of dietary energy and per-capita spending on all goods and services, to identify stylized facts about how diet cost and affordability relate to economic development and nutrition outcomes. On average, the most affordable nutrient adequate diet exceeds the cost of adequate energy by a factor of 2.66, costing US$1.35 per day to meet median requirements of healthy adult women in 2011. Affordability is lowest in Sub-Saharan Africa. The sensitivity of diet costs to each requirement reveals the high cost of staying within acceptable macronutrient ranges, particularly the upper limit for carbohydrates. Among micronutrients, total diet costs are most sensitive to requirements for calcium as well as vitamins A, C, E, B12, folate and riboflavin. On average, about 5% of dietary energy in the least-cost nutrient adequate diets is derived from animal source foods, with small quantities of meat and fish. Over 70% of all animal products in least-cost diets is eggs and dairy, but only in upper-middle and high-income countries. In lower income countries where egg and dairy prices are significantly higher, they are replaced by larger volumes of vegetal foods. When controlling for national income, diet costs are most significantly correlated with rural travel times and rural electrification. These data suggest opportunities for targeted policies and programs that reduce market prices and the cost of nutritious diets, while improving affordability through nutrition assistance, safety nets and higher earnings among low-income households.

Binaural hearing is impaired in children with hearing loss who use bilateral hearing aids.

This paper asked whether children fitted with bilateral hearing aids (BHA) develop normal perception of binaural cues which are the basis of spatial hearing. Data from children with BHA (n = 26, age = 12.6 ± 2.84 years) were compared to data from a control group (n = 12, age = 12.36 ± 2.83 years). Stimuli were 250 Hz click-trains of 36 ms and a 40 ms consonant-vowel /da/ at 1 Hz presented through ER3A insert-earphones unilaterally or bilaterally. Bilateral stimuli were presented at different interaural level difference (ILD) and interaural timing difference (ITD) conditions. Participants indicated whether the sound came from the left or right side (lateralization) or whether one sound or two could be heard (binaural fusion). BHA children lateralized ILDs similarly to the control group but had impaired lateralization of ITDs. Longer response times relative to controls suggest that lateralization of ITDs was challenging for children with BHA. Most, but not all, of the BHA group were able to fuse click and speech sounds similarly to controls. Those unable to fuse showed particularly poor ITD lateralization. Results suggest that ITD perception is abnormal in children using BHAs, suggesting persistent effects of hearing loss that are not remediated by present clinical rehabilitation protocols.

Agricultural Transformation, Nutrition Transition and Food Policy in Africa: Preston Curves Reveal New Stylised Facts.

This paper uses a Preston Curve approach to test for changes over time in agriculture, nutrition and food policy, comparing national averages in Africa and elsewhere at each level of national income per capita from the 1990s to the 2010s. Our statistical tests and data visualisations reveal that, at each level of income, African countries have faster rural population growth, a larger share of workers in agriculture and lower agricultural labour productivity than countries elsewhere, with no significant shift in these patterns from the 1990s to the 2010s. In contrast, there have been structural shifts towards less child stunting everywhere, and towards more adult obesity in high-income countries. The overall pattern of African governments' food policies and government expenditures have not shifted, however, as they continue price interventions and low investment levels characteristic of low-income countries around the world.

Head and Eye Movements Reveal Compensatory Strategies for Acute Binaural Deficits During Sound Localization.

The present study aimed to define use of head and eye movements during sound localization in children and adults to: (1) assess effects of stationary versus moving sound and (2) define effects of binaural cues degraded through acute monaural ear plugging. Thirty-three youth (MAge = 12.9 years) and seventeen adults (MAge = 24.6 years) with typical hearing were recruited and asked to localize white noise anywhere within a horizontal arc from -60° (left) to +60° (right) azimuth in two conditions (typical binaural and right ear plugged). In each trial, sound was presented at an initial stationary position (L1) and then while moving at ∼4°/s until reaching a second position (L2). Sound moved in five conditions (±40°, ±20°, or 0°). Participants adjusted a laser pointer to indicate L1 and L2 positions. Unrestricted head and eye movements were collected with gyroscopic sensors on the head and eye-tracking glasses, respectively. Results confirmed that accurate sound localization of both stationary and moving sound is disrupted by acute monaural ear plugging. Eye movements preceded head movements for sound localization in normal binaural listening and head movements were larger than eye movements during monaural plugging. Head movements favored the unplugged left ear when stationary sounds were presented in the right hemifield and during sound motion in both hemifields regardless of the movement direction. Disrupted binaural cues have greater effects on localization of moving than stationary sound. Head movements reveal preferential use of the better-hearing ear and relatively stable eye positions likely reflect normal vestibular-ocular reflexes.

Effects of Age at Implantation on Outcomes of Cochlear Implantation in Children with Short Durations of Single-Sided Deafness.

OBJECTIVE: Children with single-sided deafness (SSD) show reduced language and academic development and report hearing challenges. We aim to improve outcomes in children with SSD by providing bilateral hearing through cochlear implantation of the deaf ear with minimal delay. STUDY DESIGN: Prospective cohort study of 57 children with SSD provided with cochlear implant (CI) between May 13, 2013, and June 25, 2021. SETTING: Tertiary children's hospital. PARTICIPANTS: Children with early onset (n = 40) or later onset of SSD (n = 17) received CIs at ages 2.47 ± 1.58 years (early onset group) and 11.67 ± 3.91 years (late onset group) (mean ± SD). Duration of unilateral deafness was limited (mean ± SD = 1.93 ± 1.56 yr). INTERVENTION: Cochlear implantation of the deaf ear. MAIN OUTCOMES/MEASURES: Evaluations of device use (data logging) and hearing (speech perception, effects of spatial release from masking on speech detection, localization of stationary and moving sound, self-reported hearing questionnaires). RESULTS: Results indicated that daily device use is variable (mean ± SD = 5.60 ± 2.97, range = 0.0-14.7 h/d) with particular challenges during extended COVID-19 lockdowns, including school closures (daily use reduced by mean 1.73 h). Speech perception with the CI alone improved (mean ± SD = 65.7 ± 26.4 RAU) but, in the late onset group, remained poorer than in the normal hearing ear. Measures of spatial release from masking also showed asymmetric hearing in the late onset group ( t13 = 5.14, p = 0.001). Localization of both stationary and moving sound was poor (mean ± SD error = 34.6° ± 16.7°) but slightly improved on the deaf side with CI use ( F1,36 = 3.95, p = 0.05). Decreased sound localization significantly correlated with poorer self-reported hearing. CONCLUSIONS AND RELEVANCE: Benefits of CI in children with limited durations of SSD may be more restricted for older children/adolescents. Spatial hearing challenges remain. Efforts to increase CI acceptance and consistent use are needed.

Cathepsin S Evokes PAR2-Dependent Pain in Oral Squamous Cell Carcinoma Patients and Preclinical Mouse Models.

Oral squamous cell carcinoma (SCC) pain is more prevalent and severe than pain generated by any other form of cancer. We previously showed that protease-activated receptor-2 (PAR2) contributes to oral SCC pain. Cathepsin S is a lysosomal cysteine protease released during injury and disease that can activate PAR2. We report here a role for cathepsin S in PAR2-dependent cancer pain. We report that cathepsin S was more active in human oral SCC than matched normal tissue, and in an orthotopic xenograft tongue cancer model than normal tongue. The multiplex immunolocalization of cathepsin S in human oral cancers suggests that carcinoma and macrophages generate cathepsin S in the oral cancer microenvironment. After cheek or paw injection, cathepsin S evoked nociception in wild-type mice but not in mice lacking PAR2 in Nav1.8-positive neurons (Par2Nav1.8), nor in mice treated with LY3000328 or an endogenous cathepsin S inhibitor (cystatin C). The human oral SCC cell line (HSC-3) with homozygous deletion of the gene for cathepsin S (CTSS) with CRISPR/Cas9 provoked significantly less mechanical allodynia and thermal hyperalgesia, as did those treated with LY3000328, compared to the control cancer mice. Our results indicate that cathepsin S is activated in oral SCC, and that cathepsin S contributes to cancer pain through PAR2 on neurons.

Pediatric nasopharyngeal airways expand when exposed to saline.

PURPOSE: Nasopharyngeal airways (NPA) are commonly used to relieve upper airway obstruction in children. They must be sized to extend posterior to the tongue base but remain above the epiglottis. To avoid obstruction from nasal secretions, frequent irrigation with saline is required. We hypothesized that NPAs would swell when exposed to saline irrigation. METHODS: Twenty-five green Rusch NPA size 12, 14, 16, 18 and 20 Fr were submerged in 2 L of normal saline for 15 days. Tube length, inner diameter, outer diameter and wall thickness were measured on days 1,2,3,4,5,10, and 15 and compared using two-way repeated measures ANOVA and paired t-tests with Bonferroni correction. RESULTS: All dimensions increased significantly with exposure to saline. Increases in length, inner diameter, outer diameter and wall thickness were dependent on original tube size (p < 0.05) and duration of exposure to saline (p < 0.001). The increase in tube length was greatest over the first five days. CONCLUSION: NPAs expand significantly when exposed to saline with the greatest increase in length occurring in the first five days. This could lead to gagging or airway obstruction in small children. Patients with NPAs should be monitored closely for these signs and new materials should be sourced to prevent these issues.

Granulocyte-Colony Stimulating Factor-Induced Neutrophil Recruitment Provides Opioid-Mediated Endogenous Anti-nociception in Female Mice With Oral Squamous Cell Carcinoma.

Oral cancer patients report severe function-induced pain; severity is greater in females. We hypothesize that a neutrophil-mediated endogenous analgesic mechanism is responsible for sex differences in nociception secondary to oral squamous cell carcinoma (SCC). Neutrophils isolated from the cancer-induced inflammatory microenvironment contain ß-endorphin protein and are identified by the Ly6G+ immune marker. We previously demonstrated that male mice with carcinogen-induced oral SCC exhibit less nociceptive behavior and a higher concentration of neutrophils in the cancer microenvironment compared to female mice with oral SCC. Oral cancer cells secrete granulocyte colony stimulating factor (G-CSF), a growth factor that recruits neutrophils from bone marrow to the cancer microenvironment. We found that recombinant G-CSF (rG-CSF, 5 µg/mouse, intraperitoneal) significantly increased circulating Ly6G+ neutrophils in the blood of male and female mice within 24 h of administration. In an oral cancer supernatant mouse model, rG-CSF treatment increased cancer-recruited Ly6G+ neutrophil infiltration and abolished orofacial nociceptive behavior evoked in response to oral cancer supernatant in both male and female mice. Local naloxone treatment restored the cancer mediator-induced nociceptive behavior. We infer that rG-CSF-induced Ly6G+ neutrophils drive an endogenous analgesic mechanism. We then evaluated the efficacy of chronic rG-CSF administration to attenuate oral cancer-induced nociception using a tongue xenograft cancer model with the HSC-3 human oral cancer cell line. Saline-treated male mice with HSC-3 tumors exhibited less oral cancer-induced nociceptive behavior and had more ß-endorphin protein in the cancer microenvironment than saline-treated female mice with HSC-3 tumors. Chronic rG-CSF treatment (2.5 µg/mouse, every 72 h) increased the HSC-3 recruited Ly6G+ neutrophils, increased ß-endorphin protein content in the tongue and attenuated nociceptive behavior in female mice with HSC-3 tumors. From these data, we conclude that neutrophil-mediated endogenous opioids warrant further investigation as a potential strategy for oral cancer pain treatment.

Dipeptidyl Peptidase 4 Inhibition Stimulates Distal Tubular Natriuresis and Increases in Circulating SDF-1α1-67 in Patients With Type 2 Diabetes.

OBJECTIVE: Antihyperglycemic agents, such as empagliflozin, stimulate proximal tubular natriuresis and improve cardiovascular and renal outcomes in patients with type 2 diabetes. Because dipeptidyl peptidase 4 (DPP-4) inhibitors are used in combination with sodium-glucose cotransporter 2 (SGLT2) inhibitors, we examined whether and how sitagliptin modulates fractional sodium excretion and renal and systemic hemodynamic function. RESEARCH DESIGN AND METHODS: We studied 32 patients with type 2 diabetes in a prospective, double-blind, randomized, placebo-controlled trial. Measurements of renal tubular function and renal and systemic hemodynamics were obtained at baseline, then hourly after one dose of sitagliptin or placebo, and repeated at 1 month. Fractional excretion of sodium and lithium and renal hemodynamic function were measured during clamped euglycemia. Systemic hemodynamics were measured using noninvasive cardiac output monitoring, and plasma levels of intact versus cleaved stromal cell-derived factor (SDF)-1α were quantified using immunoaffinity and tandem mass spectrometry. RESULTS: Sitagliptin did not change fractional lithium excretion but significantly increased total fractional sodium excretion (1.32 ± 0.5 to 1.80 ± 0.01% vs. 2.15 ± 0.6 vs. 2.02 ± 1.0%, P = 0.012) compared with placebo after 1 month of treatment. Moreover, sitagliptin robustly increased intact plasma SDF-1α1-67 and decreased truncated plasma SDF-1α3-67. Renal hemodynamic function, systemic blood pressure, cardiac output, stroke volume, and total peripheral resistance were not adversely affected by sitagliptin. CONCLUSIONS: DPP-4 inhibition promotes a distal tubular natriuresis in conjunction with increased levels of intact SDF-1α1-67. Because of the distal location of the natriuretic effect, DPP-4 inhibition does not affect tubuloglomerular feedback or impair renal hemodynamic function, findings relevant to using DPP-4 inhibitors for treating type 2 diabetes.