Protective effects of diversified diets for dietary folate adequacy and serum homocysteine in breastfeeding mothers amid historic drought.

OBJECTIVES: The United Nations recommends that women consume ≥5 food groups, also known as the minimum dietary diversity score for women (MDD-W), for nutritional health. This is increasingly unattainable for populations in climate hot zones coping with food insecurity by prioritizing calories over dietary breadth. Breastfeeding mothers may be particularly vulnerable to adverse health impacts of low dietary diversity due to elevated nutritional requirements for lactation. We investigated how the protective effects of MDD-W for folate adequacy varies by MDD-W score and mother-infant life history characteristics. METHODS: We conducted a secondary analysis of cross-sectional data from breastfeeding mothers (n = 228) in northern Kenya, surveyed during the 2006 Horn-of-Africa drought. Logistic regression models for adequate dietary folate (and vitamins B12 and B6) and normal homocysteine (folate-replete status) evaluated the effect of MDD-W alone and in interaction with infant/maternal characteristics. RESULTS: MDD-W (as ordinal or dichotomous variable) was positively associated with adequate folate (and vitamin B12). Having male infant was inversely associated with adequate dietary folate. MDD-W was generally unassociated with homocysteine. However, there was an interaction between MDD-W and sex of the infant. Namely, MDD-W ≥ 3 predicted increased probability of normal homocysteine among mothers with female infants but not male infants. CONCLUSIONS: Diets consisting of three or more food groups may protect adequate folate intake for many breastfeeding mothers. More research is needed to establish what level of dietary diversity would protect against hyperhomocysteinemia during breastfeeding and what factors promote or hinder the benefit of diversified diets on maternal folate nutrition.

Maternal and infant predictors of proinflammatory milk immune activity in Kilimanjaro, Tanzania.

OBJECTIVES: The immune system of milk (ISOM) creates a mother-infant immune axis that plays an important role in protecting infants against infectious disease (ID). Tradeoffs in the immune system suggest the potential for both protection and harm, so we conceive of two dimensions via which the ISOM impacts infants: promotion of protective activity and control of activity directed at benign targets. High variability in ISOM activity across mother-infant dyads suggests investment the ISOM may have evolved to be sensitive to maternal and/or infant characteristics. We assessed predictors of appropriate and misdirected proinflammatory ISOM activity in an environment of high ID risk, testing predictions drawn from life history theory and other evolutionary perspectives. METHODS: We characterized milk in vitro interleukin-6 (IL-6) responses to Salmonella enterica (a target of protective immune activity; N = 96) and Escherichia coli (a benign target; N = 85) among mother-infant dyads in rural Kilimanjaro, Tanzania. We used ordered logistic regression and mixture models to evaluate maternal and infant characteristics as predictors of IL-6 responses. RESULTS: In all models, IL-6 responses to S. enterica increased with maternal age and decreased with gravidity. In mixture models, IL-6 responses to E. coli declined with maternal age and increased with gravidity. No other considered variables were consistently associated with IL-6 responses. CONCLUSIONS: The ISOM's capacities for appropriate proinflammatory activity and control of misdirected proinflammatory activity increases with maternal age and decreases with gravidity. These findings are consistent with the hypothesis that the mother-infant immune axis has evolved to respond to maternal life history characteristics.

Does the immune system of milk increase activity for infants experiencing infectious disease episodes in Kilimanjaro, Tanzania?

INTRODUCTION: Multiple studies have reported that milk immune content increases for infants experiencing infectious disease (ID) episodes, suggesting that the immune system of milk (ISOM) offers enhanced protection when needed to combat ID. METHODS: To test the hypothesis that ISOM content and/or activity increases during an infant's ID episode, we characterized milk secretory immunoglobulin A (sIgA; a major ISOM constituent) and in vitro interleukin-6 (IL-6) responses to Salmonella enterica and Escherichia coli, as system-level biomarkers of ISOM activity, in a prospective study among 96 mother-infant dyads in Kilimanjaro, Tanzania. RESULTS: After control for covariates, no milk immune variables (sIgA, Coef: 0.03; 95% CI -0.25, 0.32; in vitro IL-6 response to S. enterica, Coef: 0.23; 95% CI: -0.67, 1.13; IL-6 response to E. coli, Coef: -0.11; 95% CI: -0.98, 0.77) were associated with prevalent ID (diagnosed at the initial participation visit). Among infants experiencing an incident ID (diagnosed subsequent to the initial participation), milk immune content and responses were not substantially higher or lower than the initial visit (sIgA, N: 61; p: 0.788; IL-6 response to S. enterica, N: 56; p: 0.896; IL-6 response to E. coli, N: 36; p: 0.683); this was unchanged by exclusion of infants with ID at the time of initial participation. CONCLUSION: These findings are not consistent with the hypothesis that milk delivers enhanced immune protection when infants experience ID. In environments with a high burden of ID, dynamism may be less valuable to maternal reproductive success than stability in the ISOM.

Campylobacter coli infection causes spinal epidural abscess with Guillain-Barré syndrome: a case report.

BACKGROUND: Guillain-Barré syndrome (GBS) and spinal epidural abscess (SEA) are known as mimics of each other because they present with flaccid paralysis following an infection; however, they differ in the main causative bacteria. Nevertheless, the two diseases can occur simultaneously if there is a preceding Campylobacter infection. Here, we report the first case of SEA with GBS following Campylobacter coli infection. CASE PRESENTATION: A 71-year-old Japanese man presented with progressive back pain and paralysis of the lower limbs following enteritis. Magnetic resonance imaging showed a lumbar epidural abscess that required surgical decompression; therefore, surgical drainage was performed. Blood cultures revealed the presence of C. coli. Despite surgery, the paralysis progressed to the extremities. Nerve conduction studies led to the diagnosis of GBS. Anti-ganglioside antibodies in the patient suggested that GBS was preceded by Campylobacter infection. Intravascular immunoglobulin therapy attenuated the progression of the paralysis. CONCLUSIONS: We report a case of SEA and GBS following Campylobacter infection. A combination of the two diseases is rare; however, it could occur if the preceding infection is caused by Campylobacter spp. If a cause is known but the patient does not respond to the corresponding treatment, it is important to reconsider the diagnosis based on the medical history.

Human milk lactoferrin variation in relation to maternal inflammation and iron deficiency in northern Kenya.

BACKGROUND: Milk lactoferrin is a multi-functional, iron-binding glycoprotein with immunomodulatory effects, protecting infants against infectious diseases. AIMS: This study explored how maternal inflammation/infection and iron-deficiency anemia (IDA) might influence human milk lactoferrin. Lactoferrin might be elevated with maternal inflammation resulting from infectious disease processes. Conversely, lactoferrin might decrease with IDA, corresponding to scarce maternal iron for transfer in milk. In these two hypothesized scenarios, the degree of lactoferrin elevation or decrease might vary with infant vulnerability to infectious diseases or malnutrition. Alternatively, lactoferrin might be unassociated with inflammation/infection or IDA if mothers could buffer it against these conditions. MATERIALS & METHODS: We used cross-sectional data from Ariaal mothers of northern Kenya (n = 200) to evaluate associations between milk lactoferrin and maternal inflammation/infection, IDA, infant age/sex, and the mother-infant variable interactions in multivariate regression models. RESULTS: Maternal inflammation was associated with higher lactoferrin for younger infants (<~5 months of age) but with lower lactoferrin for older infants. Maternal IDA was unassociated with lactoferrin alone or in interaction with infant variables. DISCUSSION & CONCLUSION: Results suggest that mothers of vulnerable young infants deliver more lactoferrin when they have inflammation/infection but mothers with older infants do not, and that maternal delivery of lactoferrin is unaffected by their IDA. Longitudinal research should verify these findings.

The Effects of Mutual Interaction of Orexin-A and Glucagon-Like Peptide-1 on Reflex Swallowing Induced by SLN Afferents in Rats.

(1) Background: Our previous studies revealed that orexin-A, an appetite-increasing peptide, suppressed reflex swallowing via the commissural part of the nucleus tractus solitarius (cNTS), and that glucagon-like peptide-1 (GLP-1), an appetite-reducing peptide, also suppressed reflex swallowing via the medial nucleus of the NTS (mNTS). In this study, we examined the mutual interaction between orexin-A and GLP-1 in reflex swallowing. (2) Methods: Sprague-Dawley rats under urethane-chloralose anesthesia were used. Swallowing was induced by electrical stimulation of the superior laryngeal nerve (SLN) and was identified by the electromyographic (EMG) signals obtained from the mylohyoid muscle. (3) Results: The injection of GLP-1 (20 pmol) into the mNTS reduced the swallowing frequency and extended the latency of the first swallow. These suppressive effects of GLP-1 were not observed after the fourth ventricular administration of orexin-A. After the injection of an orexin-1 receptor antagonist (SB334867) into the cNTS, an ineffective dose of GLP-1 (6 pmol) into the mNTS suppressed reflex swallowing. Similarly, the suppressive effects of orexin-A (1 nmol) were not observed after the injection of GLP-1 (6 pmol) into the mNTS. After the administration of a GLP-1 receptor antagonist (exendin-4(5-39)), an ineffective dose of orexin-A (0.3 nmol) suppressed reflex swallowing. (4) Conclusions: The presence of reciprocal inhibitory connections between GLP-1 receptive neurons and orexin-A receptive neurons in the NTS was strongly suggested.

Buffered or impaired: Maternal anemia, inflammation and breast milk macronutrients in northern Kenya.

BACKGROUND: Maternal anemia has adverse consequences for the mother-infant dyad. To evaluate whether and how milk nutrient content may change in ways that could "buffer" infants against the conditions underlying maternal anemia, this study assessed associations between milk macronutrients and maternal iron-deficiency anemia (IDA), non-iron-deficiency anemia (NIDA), and inflammation. METHODS: A secondary analysis of cross-sectional data and milk from northern Kenya was conducted (n = 204). The combination of hemoglobin and transferrin receptor defined IDA/NIDA. Elevated serum C-reactive protein defined acute inflammation. The effects of IDA, NIDA, and inflammation on milk macronutrients were evaluated in regression models. RESULTS: IDA (ß = 0.077, p = .022) and NIDA (ß = 0.083, p = .100) predicted higher total protein (ln). IDA (ß = -0.293, p = .002), NIDA (ß = -0.313, p = .047), and inflammation (ß = -0.269, p = .007) each predicted lower fat (ln); however, anemia accompanying inflammation predicted higher fat (ß = 0.655, p = .007 for IDA and ß = 0.468, p = .092 for NIDA). NIDA predicted higher lactose (ß = 1.020, p = .003). CONCLUSIONS: Milk macronutrient content both increases and decreases in the presence of maternal anemia and inflammation, suggesting a more complicated and dynamic change than simple impairment of nutrient delivery during maternal stress. Maternal fat delivery to milk may be impaired under anemia. Mothers may buffer infant nutrition against adverse conditions or poor maternal health by elevating milk protein (mothers with IDA/NIDA), lactose (mothers with NIDA), or fat (mothers with anemia and inflammation). This study demonstrates the foundational importance of maternal micronutrient health and inflammation or infection for advancing the ecological understanding of human milk nutrient variation.

Variation in breast milk macronutrient contents by maternal anemia and hemoglobin concentration in northern Kenya.

OBJECTIVES: This study explored differing levels of macronutrients in breast milk in relation to maternal anemia and hemoglobin. METHODS: Archived milk specimens and data from a cross-sectional sample of 208 breastfeeding mothers in northern Kenya, originally collected in 2006, were analyzed; data included milk fat, maternal hemoglobin concentration, and anemia status (anemia defined as hemoglobin <12 g/dL). Total protein and lactose were measured and energy was calculated. To explore the association between milk outcomes (fat, protein, lactose, and energy) and anemia, regression models were constructed with and without adjustment for maternal age, parity, and time (days) postpartum. The same models were constructed using hemoglobin as a continuous predictor in lieu of dichotomous anemia to explore the role of hemoglobin levels and anemia severity in predicting milk outcomes. RESULTS: The group comparison indicated significantly higher milk protein and lower milk fat for anemic mothers relative to nonanemic counterparts. After adjustment for maternal age, parity, and time postpartum, maternal anemia was associated with significantly higher milk protein (P = 0.001) and significantly lower milk fat (P = 0.025). Hemoglobin had a significant inverse relationship with milk protein (P = 0.017) and a marginally significant positive relationship with milk fat (P = 0.060) after adjusting for the maternal variables. Neither anemia nor hemoglobin was significant in predicting lactose or milk energy. CONCLUSIONS: Maternal anemia and hemoglobin concentration may be associated with complex changes in milk macronutrients. Future research should clarify the impact of maternal anemia on a range of breast milk components while accounting for other maternal characteristics.

A test of the optimal iron hypothesis among breastfeeding Ariaal mothers in northern Kenya.

OBJECTIVE: The optimal iron hypothesis posits a trade-off in iron nutrition-iron deficiency restricts iron available to infectious agents, protecting against severe infection, but also compromises immune defense-such that mild-to-moderate iron deficiency may be more adaptive than either iron-replete or severe deficiency in environments with high infectious disease load. This hypothesis has not been tested among adults. MATERIALS AND METHODS: A secondary analysis of data and specimens from 220 lactating mothers in northern Kenya was conducted. Elevated serum C-reactive protein (CRP > 2 or >5 mg/l) was utilized to identify prevalent subclinical infection/inflammation. Iron deficiency was identified with transferrin receptor in archived dried blood spots (TfR > 5.0 mg/l). The absence of iron deficiency or anemia (Hemoglobin < 12 g/l) defined the iron replete state. Iron-deficient erythropoiesis (IDE, mild-to-moderate iron deficiency) was defined as iron deficiency without anemia; iron deficiency anemia (IDA, severe iron deficiency) as iron deficiency with anemia; and noniron-deficiency anemia (NIDA) as anemia without iron deficiency. RESULTS: The prevalence of elevated inflammation (subclinical infection) was lowest in IDE. In logistic regression, IDE was inversely associated with inflammation (for CRP > 2 mg/l: adjusted odds ratio, aOR = 0.30; p = 0.02; for CRP > 5 mg/l: aOR = 0.27; p = 0.10), compared to the iron replete state. The protective effect of IDE differed in the presence of vitamin A deficiency or underweight. CONCLUSIONS: We interpret these patterns as tentative support for the optimal iron hypothesis in breastfeeding women in the infectious disease ecology of northern Kenya. Iron deficiency may interact in important ways with other forms of malnutrition that are known to affect immune protection.

Nutritional, inflammatory, and ecological correlates of maternal retinol allocation to breast milk in agro-pastoral Ariaal communities of northern Kenya.

OBJECTIVES: Vitamin A (VA) is an essential micronutrient required for a range of biological functions throughout life. VA deficiency (VAD) claims an estimated 1 million preschool children's lives annually. Human milk is enriched with VA (retinol) from the maternal blood, which originates from the hepatic reserve and dietary intake. Secreting retinol into milk will benefit the nursing infant through breast milk, but retaining retinol is also important for the maternal health. Previous studies found that the public health intervention of high-dose VA supplementation to lactating mothers did not significantly lower child mortality. The World Health Organization (WHO) recently acknowledged that our understanding about the principle of VA allocation within the maternal system and the secretion into milk is too incomplete to devise an effective intervention. METHODS: We present a secondary analysis of data collected among lactating mothers in VAD endemic northern Kenya (n = 171), examining nutritional, inflammatory, and ecological factors that might associate with maternal retinol allocation. Regression models were applied using the outcome milk-retinol allocation index: milk retinol/(milk retinol + serum retinol). RESULTS: Ten percent of the sample was identified as VAD. The average milk retinol concentration was 0.1 µmo/L, grossly below what is considered minimally necessary for an infant (1 µmol/L). VAD mothers and mothers with inflammation did not seem to compromise their milk retinol even though their serum retinol was lower than non-VAD and noninflammation mothers. Breast milk fat concentration positively correlated with milk retinol but not with serum retinol. CONCLUSIONS: This exploratory study contributes toward an understanding of maternal retinol allocation.

Characterization of rabbit limbal epithelial side population cells using RNA sequencing and single-cell qRT-PCR.

Corneal epithelial stem cells reside in the limbus, a transitional zone between the cornea and conjunctiva, and are essential for maintaining homeostasis in the corneal epithelium. Although our previous studies demonstrated that rabbit limbal epithelial side population (SP) cells exhibit stem cell-like phenotypes with Hoechst 33342 staining, the different characteristics and/or populations of these cells remain unclear. Therefore, in this study, we determined the gene expression profiles of limbal epithelial SP cells by RNA sequencing using not only present public databases but also contigs that were created by de novo transcriptome assembly as references for mapping. Our transcriptome data indicated that limbal epithelial SP cells exhibited a stem cell-like phenotype compared with non-SP cells. Importantly, gene ontology analysis following RNA sequencing demonstrated that limbal epithelial SP cells exhibited significantly enhanced expression of mesenchymal/endothelial cell markers rather than epithelial cell markers. Furthermore, single-cell quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) demonstrated that the limbal epithelial SP population consisted of at least two immature cell populations with endothelial- or mesenchymal-like phenotypes. Therefore, our present results may propose the presence of a novel population of corneal epithelial stem cells distinct from conventional epithelial stem cells.

Nutrient intakes associated with elevated serum C-reactive protein concentrations in normal to underweight breastfeeding women in Northern Kenya.

OBJECTIVES: Low-grade elevation of C-reactive protein (CRP) is a non-specific inflammatory marker, used as a predictor for cardiovascular disease development and chronic inflammatory risks. Research investigating dietary influences on inflammation has focused primarily on the relationship between dietary characteristics, CRP elevation and BMI in the populations at greatest risk for cardiovascular disease, namely those in the overweight and obese ranges, often in clinical settings and/or among those middle aged or older, leaving little information about normal to underweight populations of reproductive age in ecological settings. This study evaluates impacts of dietary nutrients on serum CRP levels in a population of predominantly underweight to normal weight adult women experiencing the additional nutritional demands of lactation. METHODS: Data from non-overweight breastfeeding Ariaal women of Kenya collected in 2006 were used (n = 194). Logistic regression models were applied using low-grade CRP elevation (hsCRP > 3 mg/L) as the outcome variable and dietary nutrients, age, BMI, and serum retinol as predictors. RESULTS: Models showed that energy intake (Kcal) and age were positive predictors of CRP elevation while folate intake, total vitamin A intake, and serum retinol concentration were protective against CRP elevation. Unlike previous studies among higher BMI populations, this study found no significant effect of dietary lipids/fatty acids or BMI on CRP elevation. CONCLUSIONS: The effects of specific dietary nutrients on inflammatory status may vary with BMI or, in women, reproductive status. Further research should investigate the role of dietary fats, fatty acids, and antioxidant vitamins across populations with a wide range of BMI, including postpartum women.

Case report: Early-onset Parkinson's disease with lower limb spasticity in a new DJ-1/PARK7 patient.

Rare autosomal recessive variants in DJ-1, a causative gene for early-onset Parkinson's disease, have been associated with a variety of clinical syndromes in a limited number of patients. Here, we report a case of a novel DJ-1 variant in a 39-year-old man with a 4-year history of parkinsonism, cognitive dysfunction, and lower limb spasticity. He was diagnosed with Parkinson's disease. Genetic testing of the patient revealed compound heterozygous variants in the DJ-1 gene (exon 6 deletion + c.242dup), of which exon 6 deletion was a novel variant. We conclude that variants in DJ-1 should be considered possible causes of early-onset parkinsonism with spasticity and cognitive impairment, as in this case.

Field and laboratory methods in human milk research.

Human milk is a complex and variable fluid of increasing interest to human biologists who study nutrition and health. The collection and analysis of human milk poses many practical and ethical challenges to field workers, who must balance both appropriate methodology with the needs of participating mothers and infants and logistical challenges to collection and analysis. In this review, we address various collection methods, volume measurements, and ethical considerations and make recommendations for field researchers. We also review frequently used methods for the analysis of fat, protein, sugars/lactose, and specific biomarkers in human milk. Finally, we address new technologies in human milk research, the MIRIS Human Milk Analyzer and dried milk spots, which will improve the ability of human biologists and anthropologists to study human milk in field settings.

Oxytocin increased intragastric pressure in the forestomach of rats via the dorsal vagal complex.

We previously reported that appetite-enhancing peptides facilitated phasic contractions of the distal stomach and relaxed the forestomach via the dorsal vagal complex (DVC). The present study investigated the effects of anorectic substances on gastric reservoir function. The effects of oxytocin on the motility of the forestomach were examined in rats anesthetized with urethane-chloralose. Gastric motor responses were measured using an intragastric balloon. The fourth ventricular administration of oxytocin (0.1 - 1.0 nmol) increased intragastric pressure (IGP) in the forestomach in a dose-dependent manner. Conversely, the administration of oxytocin (0.3 nmol) suppressed phasic contractions of the distal stomach. These responses were opposite to those of appetite-enhancing peptides in previous studies. The oxytocin response in the forestomach was not observed after bilateral cervical vagotomy. The effects of oxytocin on forestomach motility were examined in animals that underwent ablation of the area postrema (AP) to clarify its involvement. Although the magnitude of the response to the fourth ventricular administration of oxytocin decreased, a significant response was still observed. A microinjection of oxytocin (3 pmol) into the AP, the left medial nucleus of the nucleus tractus solitarius (mNTS), the left commissural part of the NTS, or the left dorsal motor nucleus of the vagus was performed. The oxytocin injection into the AP and/or mNTS induced a rapid and large increase in IGP in the forestomach. Prior injection of L-368,899, an oxytocin receptor antagonist, into both the AP and mNTS attenuated the oxytocin response of the forestomach induced by fourth ventricular administration of oxytocin. These results indicate that oxytocin acts on the AP and/or mNTS to increase IGP in the forestomach via vagal preganglionic neurons.

In poor families, mothers' milk is richer for daughters than sons: a test of Trivers-Willard hypothesis in agropastoral settlements in Northern Kenya.

The Trivers-Willard hypothesis predicts the unequal parental investment between daughters and sons, depending on maternal condition and offspring reproductive potential. Specifically, in polygynous populations where males have higher reproductive variance than females, it predicts that mothers in good condition will invest more in sons, whereas mothers in poor condition will invest more in daughters. Previous studies testing this hypothesis focused on behavioral investment, whereas few examined biological investment. This study investigates the Trivers-Willard hypothesis on both behavioral and biological parental investment by examining breastfeeding frequencies and breast milk fat concentrations. Data from exclusively breastfeeding mothers in Northern Kenya were used to test hypotheses: Economically sufficient mothers will breastfeed sons more frequently than daughters, whereas poor mothers will breastfeed daughters more frequently than sons, and economically sufficient mothers will produce breast milk with higher fat concentration for sons than daughters, whereas poor mothers will produce breast milk with higher fat concentration for daughters than sons. Linear regression models were applied, using breastfeeding frequency or log-transformed milk fat as the dependent variable, and offspring's sex (son = 1/daughter = 0), socioeconomic status (higher = 1/lower = 0), and the sex-wealth interaction as the predictors, controlling for covariates. Our results only supported the milk fat hypothesis: infant's sex and socioeconomic status interacted (P = 0.014, n = 72) in their relation with milk fat concentration. The model estimated that economically sufficient mothers produced richer milk for sons than daughters (2.8 vs. 1.74 gm/dl) [corrected] while poor mothers produced richer milk for daughters than sons (2.6 vs. 2.3 gm/dl). Further research on milk constituents in relation to offspring's sex is warranted.

Dietary diversity score is a useful indicator of vitamin A status of adult women in Northern Kenya.

OBJECTIVES: Diets consisting of diverse food items provide a wide range of nutrients that can enhance nutritional quality of the diet. Few studies have, however, assessed dietary diversity and its effects on micronutrient health in rural populations in field settings. This study assesses how well Dietary Diversity Score (DDS), an indicator of dietary diversity based on a simple count of food groups consumed, predicts the micronutrient status, focusing on serum vitamin A concentration. METHODS: We used cross-sectional data from women in food-insecure northern Kenya where dietary diversity is likely critical for micronutrient health yet under-studied. A linear regression model was applied to examine the relationships between DDS and serum retinol concentration. A logistic regression model was used to test DDS as a predictor of vitamin A insufficiency (serum retinol < 1.05 µmol/l). RESULTS: DDS had a significant positive effect on serum retinol concentration (t = 2.01, P = 0.045) after adjusting for age, wealth, acute phase reaction, hemoglobin, vitamin A intake and vitamin A supplementation. A one unit increase in DDS by adding an extra food group in one's diet was significantly less likely to have vitamin A insufficiency (OR = 0.64, P = 0.026) after adjusting for the covariates. CONCLUSIONS: Our results indicate that diversified diets enhance vitamin A status relative to narrower diets with equivalent vitamin A content. DDS shows a potential as a low-cost, field-friendly method for exploratory assessments of vitamin A status, and a potential as a research tool for human biologists and anthropologists interested in dietary quality and micronutrient health.

Case report: Adult-onset neuronal intranuclear inclusion disease with an amyotrophic lateral sclerosis phenotype.

Amyotrophic lateral sclerosis (ALS) is one of the differential diagnoses of diseases that occur in adulthood and lead to progressive generalized muscle weakness. Neuronal intranuclear inclusion disease (NIID) is a disease in which histopathologically eosinophilic nuclear inclusion bodies are found in various systems. Both familial and sporadic forms of the disease have been reported. Most cases of sporadic NIID are of the dementia type, in which the main symptom is dementia at the first onset. Familial NIID is more diverse, with the main dominant symptoms being muscle weakness (NIID-M), dementia (NIID-D), and parkinsonism (NIID-P). Furthermore, recently, a GGC-repeat expansion in the Notch 2 N-terminal like C (NOTCH2NLC) gene, which produces a toxic polyglycine-containing protein (uN2CpolyG) in patients with NIID, has been associated with the pathogenesis of ALS. These results suggest that sporadic NIIDs may have more diverse forms. To date, no autopsy cases of NIID patients with an ALS phenotype have been reported. Here, we describe the first autopsy case report of a patient with sporadic NIID who had been clinically diagnosed with ALS. A 65-year-old Japanese man with no family history of neuromuscular disease developed progressive muscle atrophy and weakness in all limbs. The patient was diagnosed with ALS (El Escoriral diagnostic criteria: probable ALS, laboratory-supported ALS). He had no cognitive dysfunction or neuropathies suggestive of NIID. He required respiratory assistance 48 months after onset. He died of pneumonia at the age of 79 years. Postmortem examinations revealed neuronal loss in the spinal anterior horns and motor cortex. In these affected regions, eosinophilic, round neuronal intranuclear inclusions were evident, which were immunopositive for ubiquitin, p62, and uN2CpolyG. No Bunina bodies or TDP-43-positive inclusions were observed in the brain or spinal cord. Our findings suggest that a small proportion of patients with NIID can manifest a clinical phenotype of ALS. Although skin biopsy is commonly used for the clinical diagnosis of NIID, it may also be useful to identify cases of NIID masquerading as ALS.

Tradeoffs in milk immunity affect infant infectious disease risk.

Background and objectives: The human immune system has evolved to balance protection against infection with control of immune-mediated damage and tolerance of commensal microbes. Such tradeoffs between protection and harm almost certainly extend to the immune system of milk. Methodology: Among breastfeeding mother-infant dyads in Kilimanjaro, Tanzania, we characterized in vitro proinflammatory milk immune responses to Salmonella enterica (an infectious agent) and Escherichia coli (a benign target) as the increase in interleukin-6 after 24 h of incubation with each bacterium. We characterized incident infectious diseases among infants through passive monitoring. We used Cox proportional hazards models to describe associations between milk immune activity and infant infectious disease. Results: Among infants, risk for respiratory infections declined with increasing milk in vitro proinflammatory response to S. enterica (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.54, 0.86; P: 0.001), while risk for gastrointestinal infections increased with increasing milk in vitro proinflammatory response to E. coli (HR: 1.44; 95% CI: 1.05, 1.99; P: 0.022). Milk proinflammatory responses to S. enterica and E. coli were positively correlated (Spearman's rho: 0.60; P: 0.000). Conclusions and implications: These findings demonstrate a tradeoff in milk immune activity: the benefits of appropriate proinflammatory activity come at the hazard of misdirected proinflammatory activity. This tradeoff is likely to affect infant health in complex ways, depending on prevailing infectious disease conditions. How mother-infant dyads optimize proinflammatory milk immune activity should be a central question in future ecological-evolutionary studies of the immune system of milk.