Access to Workplace Supports is Positively Associated with Exclusive Breastfeeding among Formally Employed Mothers in Kenya.

BACKGROUND: Mothers in low-income settings who work in agricultural employment are challenged to meet breastfeeding (BF) recommendations. Recent legislation in Kenya mandates maternity leave and workplace supports, yet the relation of these benefits with BF practices is poorly understood. OBJECTIVES: We evaluated the associations with workplace-provided BF supports and BF practices among formally employed mothers in Kenya. The availability of supports was hypothesized to be associated with a higher prevalence and greater odds of exclusive breastfeeding (EBF). METHODS: We conducted repeated cross-sectional surveys among formally employed mothers at 1-4 d and 6, 14, and 36 wk (to estimate 24 wk) postpartum in Naivasha, Kenya. We used logistic regression adjusted for maternal age, education, physical burden of work, HIV status, and income to evaluate associations between workplace supports and EBF practices. RESULTS: Among formally employed mothers (n = 564), those who used onsite workplace childcare were more likely to practice EBF than those who used community- or home-based childcare at both 6 wk (95.7% compared with 82.4%, P = 0.030) and 14 wk (60.6% compared with 22.2%, P < 0.001; adjusted OR: 5.11; 95% CI: 2.3, 11.7). Likewise, at 14 wk among mothers who currently used daycare centers, a higher proportion of mothers who visited daycare centers at or near workplaces practiced EBF (70.0%) than of those not visiting daycare centers (34.7%, P = 0.005). EBF prevalence was higher among mothers with access to workplace private lactation spaces than among mothers without such spaces (84.6% compared with 55.6%, P = 0.037), and among mothers who lived in workplace housing than those without onsite housing (adjusted OR: 2.06, 95% CI: 1.25, 3.41). CONCLUSIONS: Formally employed mothers in Kenya who have access to and use workplace-provided BF supports were more likely to practice EBF than mothers who lacked these supports. As the Kenya Health Act is implemented, lactation rooms, onsite housing and daycare, and transportation to visit children can all support BF and EBF among employed mothers.

Formal maternal employment is associated with lower odds of exclusive breastfeeding by 14 weeks postpartum: a cross-sectional survey in Naivasha, Kenya.

BACKGROUND: In many low- and middle-income countries, improvements in exclusive breastfeeding (EBF) have stalled, delaying reductions in child mortality. Maternal employment is a potential barrier to EBF. OBJECTIVES: We evaluated associations between maternal employment and breastfeeding (BF) status. We compared formally and non-formally employed mothers in Naivasha, Kenya, where commercial floriculture and hospitality industries employ many women. METHODS: We conducted a cross-sectional survey among mothers (n = 1186) from September 2018 to October 2019 at 4 postpartum time points: at hospital discharge (n = 296) and at 6 wk (n = 298), 14 wk (n = 295), and 36 wk (to estimate BF at 24 wk; n = 297) postpartum. Mothers reported their BF status and reasons for EBF cessation. We used multivariable logistic regression models to test the association between formal maternal employment and 3 outcomes: early BF initiation (within 1 h of birth), EBF at each time point, and continued BF at 9 mo. Models were informed by a directed acyclic graph: a causal diagram used to characterize the relationship among variables that influence the independent (employment) and dependent (BF status) variables. RESULTS: EBF did not differ by employment status at hospital discharge or at 6 wk postpartum. However, formally employed mothers were less likely than those not formally employed to report EBF at 14 wk (59.0% compared with 95.4%, respectively; AOR: 0.19; 95% CI: 0.10, 0.34) and at 24 wk (19.0% compared with 49.6%, respectively; AOR: 0.25; 95% CI: 0.14, 0.44). The prevalence of continued BF at 36 wk did not differ by group (98.1% for formally employed compared with 98.5% for non-formally employed women; AOR: 0.80; 95% CI: 0.10, 6.08). The primary reasons reported for early EBF cessation were returning to work (46.5%), introducing other foods based on the child's age (33.5%), or perceived milk insufficiency (13.7%). CONCLUSIONS: As more women engage in formal employment in low- and middle-income countries, additional supports to help prolong the period of EBF may be beneficial for formally employed mothers and their children.

Diet quality on days without breakfast or lunch - Identifying targets to improve adolescents' diet.

Dietary intake in adolescents does often not align with the recommended dietary guidelines. Excess intakes of added sugar and saturated fat, and insufficient vegetable intake are among the identified challenges, which can affect future health negatively. Identifying targets to improve dietary practices is therefore essential. The current study aimed to examine the prevalence of meal skipping and if meal skipping days had a different diet quality than other days, using data from a recent Norwegian dietary survey in adolescents (n = 689, age 12-14 years). Their dietary intake was recorded for four days, using a web-based record system. Differences between days with, and without, breakfast or lunch were explored using mixed effect models, adjusting for correlated data and covariates, including weekday-weekend effect. In total, 8% and 11% were days without breakfast and lunch, respectively. Days with breakfast or lunch were associated with higher intake of fibre, and higher odds of consuming fruits and berries, juice and smoothie, than days without breakfast or lunch. Weekdays with lunch were also associated with lower intakes of added sugar and total fat (in % of energy), and discretionary foods, compared to weekdays without lunch. Skipping breakfast and lunch was associated with reduced diet quality in adolescents. Targeting these meals, and in particular school lunch, is a potential way forward to improve adolescents' dietary intake.

A Titan but not necessarily a ruler: assessing the role of titin during thick filament patterning and assembly.

The sarcomeres of striated muscle are among the most elaborate and dynamic eukaryotic cellular protein machinery, and the mechanisms by which these semicrystalline filament networks are initially patterned and assembled remain contentious. In addition to the acto-myosin filaments that provide motor function, the sarcomere contains titin filaments, comprised of individual molecules of the giant Ig- and fibronectin domain-rich protein titin. Titin is the largest known protein, containing many structurally distinct domains with a variety of proposed functions, including sarcomere stabilization, the prevention of over-stretching, and returning to resting length after contraction. One molecule of titin, which binds to both the Z-disk and the M-line, spans a half-sarcomere, and is proposed to serve as a "molecular ruler" that dictates the spacing of sarcomeres. The semirigid rod-like A-band region of titin has also been proposed to act as a scaffold for thick filament formation during muscle development, but despite decades of research, this hypothesis has not been rigorously tested. Recent studies in zebrafish have brought into question the necessity for the A-band region of titin during the early stages of sarcomere patterning. In this review, we give an overview of the many different roles of titin in the development and function of striated muscle, and address the validity of the "molecular ruler" model of myofibrillogenesis in light of the current literature.

Unc45b is essential for early myofibrillogenesis and costamere formation in zebrafish.

Despite the prevalence of developmental myopathies resulting from muscle fiber defects, the earliest stages of myogenesis remain poorly understood. Unc45b is a molecular chaperone that mediates the folding of thick-filament myosin during sarcomere formation; however, Unc45b may also mediate specific functions of non-muscle myosins (NMMs). unc45b Mutants have specific defects in striated muscle development, which include myocyte detachment indicative of dysfunctional adhesion complex formation. Given the necessity for non-muscle myosin function in the formation of adhesion complexes and premyofibril templates, we tested the hypothesis that the unc45b mutant phenotype is not mediated solely by interaction with muscle myosin heavy chain (mMHC). We used the advantages of a transparent zebrafish embryo to determine the temporal and spatial patterns of expression for unc45b, non-muscle myosins and mMHC in developing somites. We also examined the formation of myocyte attachment complexes (costameres) in wild-type and unc45b mutant embryos. Our results demonstrate co-expression and co-regulation of Unc45b and NMM in myogenic tissue several hours before any muscle myosin heavy chain is expressed. We also note deficiencies in the localization of costamere components and NMM in unc45b mutants that is consistent with an NMM-mediated role for Unc45b during early myogenesis. This represents a novel role for Unc45b in the earliest stages of muscle development that is independent of muscle mMHC folding.

The titin A-band rod domain is dispensable for initial thick filament assembly in zebrafish.

The sarcomeres of skeletal and cardiac muscle are highly structured protein arrays, consisting of thick and thin filaments aligned precisely to one another and to their surrounding matrix. The contractile mechanisms of sarcomeres are generally well understood, but how the patterning of sarcomeres is initiated during early skeletal muscle and cardiac development remains uncertain. Two of the most widely accepted hypotheses for this process include the "molecular ruler" model, in which the massive protein titin defines the length of the sarcomere and provides a scaffold along which the myosin thick filament is assembled, and the "premyofibril" model, which proposes that thick filament formation does not require titin, but that a "premyofibril" consisting of non-muscle myosin, α-actinin and cytoskeletal actin is used as a template. Each model posits a different order of necessity of the various components, but these have been difficult to test in vivo. Zebrafish motility mutants with developmental defects in sarcomere patterning are useful for the elucidation of such mechanisms, and here we report the analysis of the herzschlag mutant, which shows deficits in both cardiac and skeletal muscle. The herzschlag mutant produces a truncated titin protein, lacking the C-terminal rod domain that is proposed to act as a thick filament scaffold, yet muscle patterning is still initiated, with grossly normal thick and thin filament assembly. Only after embryonic muscle contraction begins is breakdown of sarcomeric myosin patterning observed, consistent with the previously noted role of titin in maintaining the contractile integrity of mature sarcomeres. This conflicts with the "molecular ruler" model of early sarcomere patterning and supports a titin-independent model of thick filament organization during sarcomerogenesis. These findings are also consistent with the symptoms of human titin myopathies that exhibit a late onset, such as tibial muscular dystrophy.

At the Start of the Sarcomere: A Previously Unrecognized Role for Myosin Chaperones and Associated Proteins during Early Myofibrillogenesis.

The development of striated muscle in vertebrates requires the assembly of contractile myofibrils, consisting of highly ordered bundles of protein filaments. Myofibril formation occurs by the stepwise addition of complex proteins, a process that is mediated by a variety of molecular chaperones and quality control factors. Most notably, myosin of the thick filament requires specialized chaperone activity during late myofibrillogenesis, including that of Hsp90 and its cofactor, Unc45b. Unc45b has been proposed to act exclusively as an adaptor molecule, stabilizing interactions between Hsp90 and myosin; however, recent discoveries in zebrafish and C. elegans suggest the possibility of an earlier role for Unc45b during myofibrillogenesis. This role may involve functional control of nonmuscle myosins during the earliest stages of myogenesis, when premyofibril scaffolds are first formed from dynamic cytoskeletal actin. This paper will outline several lines of evidence that converge to build a model for Unc45b activity during early myofibrillogenesis.

Cellular differentiation in primary cell cultures from single zebrafish embryos as a model for the study of myogenesis.

Culturing cells in vitro can produce a uniform population for the study of cellular differentiation, which is especially useful for the quantification of gene expression or the observation of subcellular structures. In zebrafish, a handful of immortalized cell lines have been used for these purposes, despite being heavily selected by passaging. Methods for primary cell culture of zebrafish embryonic blastomeres have been previously reported, but require combining a large number of genetically heterogeneous embryos, meaning that subsequent cell cultures are not clonal. Without genetically uniform cultures, this model system cannot exploit the wealth of available embryonic lethal mutants in zebrafish. We therefore describe methods for the generation of zebrafish embryonic blastomere cell cultures from single genetically characterized embryos. We examined myogenic differentiation and gene expression in single-embryo cultures from early wild-type embryos, as well as embryos containing an embryonic lethal mutation of unc45b, a myosin chaperone known to be required for sarcomere organization during myogenesis. We also demonstrated the practical usefulness of this technique by experimentally manipulating expression of specific genes in individual embryos before cell culture using standard tools of zebrafish biology such as morpholino-oligonucleotide gene knockdown and transgene-mediated gene expression.

Central nervous system occurrence in elderly patients with aggressive lymphoma and a long-term follow-up.

BACKGROUND: Secondary central nervous system (CNS) involvement by aggressive lymphoma is a well-known and dreadful clinical complication. The incidence and risk factors for CNS manifestation were studied in a large cohort of elderly (>60 years) patients with aggressive lymphoma. PATIENTS AND METHODS: In all, 444 previously untreated patients were randomized to receive 3-weekly combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone or cyclophosphamide, mitoxantrone, vincristine and prednisone (CNOP) (doxorubicin substituted by mitoxantrone) chemotherapy with or without filgrastim. Prophylactic intrathecal methotrexate was given to patients with lymphoma involvement of bone marrow, testis and CNS near sites. RESULTS: In all 29 of 444 (6.5%) developed CNS disease after a median observation time of 115 months. CNS was the only site of progression/relapse in 13 patients while part of a systemic disease manifestation in 16 patients. In univariate risk factor analysis, CNS occurrence was associated with extranodal involvement of testis (P = 0.002), advanced clinical stage (P = 0.005) and increased age-adjusted International Prognostic Index score (aaIPI; P = 0.035). In multivariate analysis, initial involvement of testis remained significant and clinical stage was of borderline significance. The median survival time was 2 months after presentation of CNS disease. CONCLUSION: A significant proportion of elderly patients with advanced aggressive lymphoma will develop CNS disease. CNS occurrence is related to testis involvement, advanced clinical stage and high aaIPI and the prognosis is dismal.

BEAM+autologous stem cell transplantation in malignant lymphoma: 100 consecutive transplants in a single centre. Efficacy, toxicity and engraftment in relation to stem-cell source and previous treatment.

One hundred consecutive patients with malignant lymphoma treated with high-dose chemotherapy and autologous stem cell transplantation, followed at least 1 yr post-transplant, are reported, 68 with non-Hodgkin's lymphoma and 32 with Hodgkin's disease. At transplant, 23 patients were in first remission, 69 in later chemosensitive disease and 8 were chemotherapy resistant. Based on previous treatment and stem-cell source, the patients were subdivided into 3 cohorts: BMT1: bone-marrow harvest and transplant after > or =3 treatment regimens (38 patients); BMT2: bone marrow harvest and transplant after less than 3 treatment regimens (24 patients); PBSCT: peripheral-blood stem cell transplant (38 patients, 5 of these with CD34+ cell selected PBSC). The 4-yr survival and progression-free survival of all patients was 45 and 40%, respectively. Forty-one patients have died, 27 of lymphoma, evenly distributed in the cohorts. Fourteen treatment-related deaths occurred, 13 of these in the BMT1 cohort, significantly more than in the other cohorts (p=0.001). In univariate survival analysis cohort, age, disease status at transplant and number of previous treatment regimens were significant. In multivariate survival analysis cohort, age and sex were independently significant, women having a shorter survival. The patients transplanted with unselected PBSC had significantly shorter duration of pancytopenia and hospital stay than the otherwise comparable BMT2 patients, but their progression-free survival was identical. We confirm that high-dose therapy with autologous stem cell transplant from blood or bone marrow in not-too-heavily pretreated patients is a safe procedure but will cure only half the patients.

High risk of therapy-related leukemia after BEAM chemotherapy and autologous stem cell transplantation for previously treated lymphomas is mainly related to primary chemotherapy and not to the BEAM-transplantation procedure.

A cohort of 76 patients with previous chemotherapy for Hodgkin's disease and non-Hodgkin lymphomas received high-dose carmustine, etoposide, cytosine-arabinoside and melphalan (BEAM) followed by autologous stem cell transplantation (ASCT) and was followed for relapse and development of leukemic complications. Six patients, four with Hodgkin's disease and two with non-Hodgkin lymphomas, developed leukemic complications, myelodysplasia (MDS) in four cases and overt acute myeloid leukemia (AML) in two. All six showed an abnormal karyotype, in four of them highly characteristic of therapy-related MDS (t-MDS) and therapy-related AML (t-AML). The cumulative risk of t-MDS and t-AML increased from 16 months after start of the primary chemotherapy for lymphoma and reached 17.3% (s.e. 8.5%) after 74 months. If calculated from start of BEAM and ASCT, the cumulative risk increased as early as 4 months and reached 24.3% (s.e. 12.9%) after 43 months. For the whole course of the disease, the relative risk (RR) of AML was 357 (95% CI: 43-1290), as two overt leukemias were observed vs 0.0056 expected cases of de novo AML. In the present cohort the risk of t-MDS and t-AML although high, did not differ from our previous experience in patients treated conventionally for Hodgkin's disease and non-Hodgkin lymphomas, and did not differ for patients receiving stem cells isolated from the bone marrow as compared to patients receiving stem cells isolated from peripheral blood. Antecedent chemotherapy seems to be the critical factor for the development of t-MDS and t-AML rather than the BEAM and ASCT regimen, which however may accelerate the evolution of the disease.

Parvovirus B19 infections in patients with chronic anemia.

BACKGROUND AND OBJECTIVE: Parvovirus B19 has a marked tropism for erythroid progenitor cells and this may lead to chronic anemia in predisposed individuals. It was the purpose of the present study to investigate prospectively the frequency of parvovirus B19 infections in patients with a diagnosis of chronic anemia. METHODS AND RESULTS: Evidence of parvovirus B19 infection was found in 13/43 (30%) patients by demonstrating viral DNA and/or specific IgM antibodies through the use of PCR and ELISA techniques. Parvovirus B19 infection was established in 4 of 7 patients with hemolytic anemia, in 2 of 3 patients with pure red cell aplasia, in 2 of 9 patients with myelodysplastic syndrome, and in 2 of 10 patients with aplastic anemia. In 8 of the 13 positive patients only parvovirus B19 DNA could be detected, while 4 patients tested positive for both parvovirus B19 DNA and specific IgM. In the remaining positive patient only specific IgM could be detected. CONCLUSIONS: Since no predictive paraclinical or clinical features were observed we recommend that all cases of chronic anemia be tested for the presence of parvovirus B19 infection. Due to the discrepancies between DNA and IgM results, the diagnostic procedures should include a search for specific DNA by PCR methods if specific IgM has been found to be negative.

Failure to thrive in HIV-infected children: incidence, prevalence, and clinical correlates.

"Failure to thrive" is a frequent component of the acquired immunodeficiency syndrome (AIDS) in childhood. This retrospective study was conducted to document the incidence, prevalence, and clinical correlates of "failure to thrive" in a cohort of 97 HIV-infected children seen at a large urban teaching hospital over an 8-year period. "Failure to thrive" was defined as percent of body weight for height age < or = 90%. The cumulative incidence of failure to thrive in our cohort was 37/97 (38%), with a current prevalence of 13/97 (14%). When 33 patients with severe symptomatic HIV infection [Centers for Disease Control (CDC) class C] were analyzed separately, the cumulative incidence rose to 22/33 (67%) and current prevalence to 9/33 (27%). CDC class C correlated with failure to thrive (p < 0.001), as did absolute CD4 cell count more than two standard deviations below the mean for age (p < 0.001). Neither the mode of acquisition of HIV infection nor the presence of HIV antigenemia correlated with failure to thrive. During follow-up, 34/37 patients with failure to thrive gained weight; in 17 this was associated with specific nutritional therapy. Treatment with zidovudine (AZT) was also associated with a significant weight gain (p < 0.01). The incidence and prevalence of failure to thrive in our cohort are lower than in previous reports. We conclude that enrollment of HIV-infected children in a comprehensive clinic providing nutritional evaluation, supplemental feeding, treatment of opportunistic infections, antiretroviral medications, and psychosocial support will likely continue to reduce the incidence and prevalence of "failure to thrive."

Estimation of serum concentration of parvovirus B19 DNA by PCR in patients with chronic anaemia.

Parvovirus B19 DNA was detected in serum samples from 10 out of 42 patients with chronic anaemia, the majority of whom suffered from aplastic anaemia, haemolytic anaemia, pure red cell anaemia or myelodysplastic syndrome. Nested PCR methods with sensitivities of 0.005-0.05 fg DNA were developed. In nine patients, B19 DNA could only be detected by nested PCR. Conventional PCR with a sensitivity of 50 fg B19 DNA could only detect B19 DNA in one patient. In the majority of B19-DNA-positive patients, the DNA concentration was estimated at 0.005-0.05 fg per 5 microliters serum.

Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man.

We studied the effect of intravenous infusion of synthetic truncated GLP-1 (proglucagon 78-107-amide) on fasting and postprandial gastric acid secretion, gastric emptying, and pancreatic secretion of trypsin and lipase in eight normal volunteers using marker dilution and aspiration technique. The infusion resulted in a plasma concentration of 110 +/- 14 pmol/liter (mean +/- SEM). Truncated GLP-1 significantly inhibited postprandial acid secretion by 43 +/- 11% in spite of unchanged plasma gastrin concentration. Gastric emptying rate decreased significantly; 50% emptying time increased from 16 +/- 2 min to 30 +/- 5 min. Postprandial trypsin and lipase outputs were significantly inhibited by 47 +/- 17% and 40 +/- 9% during truncated GLP-1 infusion. Pancreatic enzyme output was linearly correlated to gastric emptying, and truncated GLP-1 did not affect this relationship, suggesting that the effect on pancreatic secretion was secondary to the effect on gastric emptying. Postprandial insulin and glucagon concentrations were similar with and without truncated GLP-1 infusion in spite of significantly lower blood glucose levels (5.2 +/- 0.2 versus 3.7 +/- 0.3), indicating that GLP-1 stimulated insulin secretion and inhibited glucagon secretion. In conclusion, our results suggest that truncated GLP-1 act as a physiological inhibitor of gastric and pancreatic functions in man.

The effect of the cholecystokinin receptor antagonist MK-329 on meal-stimulated pancreaticobiliary output in humans.

To determine the physiological role of circulating cholecystokinin (CCK), the effect of the CCK receptor antagonist MK-329 on upper digestive processes was investigated in six normal volunteers after a mixed meal. In a double-blind, two-period, randomized crossover design, the subjects received either 10 mg MK-329 or placebo orally 3 hours 15 minutes before the meal, which contained 51CrCl3 as food marker. A five-lumen tube with the tip in the distal duodenum allowed continuous marker infusion (57Co-B12) and duodenal aspiration as well as recordings of antral and duodenal motility patterns via three pressure sensors. Postprandially, MK-329 caused a significant reduction of 30%-60% (P less than 0.05) in pancreatic trypsin output during the initial three 15-minute periods; thereafter, the output was virtually the same than after placebo. Thus, the integrated enzyme response was only reduced by 15% (NS) during the 3-hour period beginning 15 minutes after the meal. In contrast, gallbladder contraction, determined by total bile acid excretion, was inhibited by 77% (P less than 0.05), indicating a crucial role of CCK in regulating gallbladder motility. Except for the initial 30 minutes postprandially, MK-329 also induced a significant reduction in duodenal pH with mean values ranging from 3.5 +/- 0.2 to 4.1 +/- 0.3 compared with 4.5 +/- 0.3 to 5.0 +/- 0.4 after placebo (P less than 0.05), probably because of lowered secretion of pancreatic bicarbonate. Gastric emptying rate was significantly accelerated by MK-329 during the initial 75 minutes after the meal, but the time for 50% emptying did not differ from placebo [127.5 +/- 7.7 vs. 140.0 +/- 9.0 minutes (NS)]. No changes were observed in the motility pattern of the proximal duodenum after feeding. Whereas MK-329 only caused a slight increase of the basal plasma CCK concentrations, the postprandial levels were markedly enhanced. Peak concentrations were 10.0 +/- 1.3 vs. 4.0 +/- 0.5 pmol/L after placebo (P less than 0.001), and the integrated response exceeded the control value by 175% (P less than 0.01). The results suggest that circulating CCK is not an essential mediator of the postprandial pancreatic enzyme secretion in humans, whereas it plays a critical role in gallbladder emptying.

[Pulmonary sarcoidosis or intrathoracic malignant lymphoma--the significance of a histological diagnosis]. / Pulmonal sarkoidose kontra intratorakalt malignt lymfom--betydningen af en histologisk diagnose.

The clinical appearance of sarcoidosis and the changes seen on x-ray of the thorax are often typical. However, several other conditions may present the same symptoms and identical x-ray findings. The present case report emphasizes the importance of an invasive approach and of histological investigation in patients in whom carcoidosis is suspected. For almost one year, a man aged 29 years was considered to be suffering from sarcoidosis on account of the clinical symptoms and bilateral hilar adenitis on x-ray op the thorax. He was treated with steroid for several months with clinical and radiological response. After the illness has lasted for one year, bronchoscopy was performed and bronchial biopsies revealed the diagnosis of malignant lymphoma.