Willingness to vaccinate children against COVID-19 declined during the pandemic.

OBJECTIVES: To document the level of vaccine hesitancy in caregivers' of children younger than 12 years of age over the course of the pandemic in Pediatric Emergency Departments (ED). Study design Ongoing multicenter, cross-sectional survey of caregivers presenting to 19 pediatric EDs in the USA, Canada, Israel, and Switzerland during first months of the pandemic (phase1), when vaccines were approved for adults (phase2) and most recently when vaccines were approved for children (phase3). RESULTS: Willingness to vaccinate rate declined over the study period (59.7%, 56.1% and 52.1% in the three phases). Caregivers who are fully vaccinated, who have higher education, and those worried their child had COVID-19 upon arrival to the ED, were more likely to plan to vaccinate in all three phases. Mothers were less likely to vaccinate early in the pandemic, but this hesitancy attenuated in later phases. Older caregivers were more willing to vaccinate, and caregivers of older children were less likely to vaccinate their children in phase 3. During the last phase, willingness to vaccinate was lowest in those who had a primary care provider but did not rely on their advice for medical decisions (34%). Those with no primary care provider and those who do and rely on their medical advice, had similar rates of willingness to vaccinate (55.1% and 52.1%, respectively). CONCLUSIONS: COVID-19 vaccine hesitancy is widespread and growing over time, and public health measures should further try to leverage identified factors associated with hesitancy in order to enhance vaccination rates among children.

Retrograde signaling by a mtDNA-encoded non-coding RNA preserves mitochondrial bioenergetics.

Alveolar epithelial type II (AETII) cells are important for lung epithelium maintenance and function. We demonstrate that AETII cells from mouse lungs exposed to cigarette smoke (CS) increase the levels of the mitochondria-encoded non-coding RNA, mito-RNA-805, generated by the control region of the mitochondrial genome. The protective effects of mito-ncR-805 are associated with positive regulation of mitochondrial energy metabolism, and respiration. Levels of mito-ncR-805 do not relate to steady-state transcription or replication of the mitochondrial genome. Instead, CS-exposure causes the redistribution of mito-ncR-805 from mitochondria to the nucleus, which correlated with the increased expression of nuclear-encoded genes involved in mitochondrial function. These studies reveal an unrecognized mitochondria stress associated retrograde signaling, and put forward the idea that mito-ncRNA-805 represents a subtype of small non coding RNAs that are regulated in a tissue- or cell-type specific manner to protect cells under physiological stress.

Cascading influence of inorganic nitrogen sources on DOM production, composition, lability and microbial community structure in the open ocean.

Nitrogen frequently limits oceanic photosynthesis and the availability of inorganic nitrogen sources in the surface oceans is shifting with global change. We evaluated the potential for abrupt increases in inorganic N sources to induce cascading effects on dissolved organic matter (DOM) and microbial communities in the surface ocean. We collected water from 5 m depth in the central North Pacific and amended duplicate 20 liter polycarbonate carboys with nitrate or ammonium, tracking planktonic carbon fixation, DOM production, DOM composition and microbial community structure responses over 1 week relative to controls. Both nitrogen sources stimulated bulk phytoplankton, bacterial and DOM production and enriched Synechococcus and Flavobacteriaceae; ammonium enriched for oligotrophic Actinobacteria OM1 and Gammaproteobacteria KI89A clades while nitrate enriched Gammaproteobacteria SAR86, SAR92 and OM60 clades. DOM resulting from both N enrichments was more labile and stimulated growth of copiotrophic Gammaproteobacteria (Alteromonadaceae and Oceanospirillaceae) and Alphaproteobacteria (Rhodobacteraceae and Hyphomonadaceae) in weeklong dark incubations relative to controls. Our study illustrates how nitrogen pulses may have direct and cascading effects on DOM composition and microbial community dynamics in the open ocean.

Control of a genetic regulatory network by a selector gene.

The formation of many complex structures is controlled by a special class of transcription factors encoded by selector genes. It is shown that SCALLOPED, the DNA binding component of the selector protein complex for the Drosophila wing field, binds to and directly regulates the cis-regulatory elements of many individual target genes within the genetic regulatory network controlling wing development. Furthermore, combinations of binding sites for SCALLOPED and transcriptional effectors of signaling pathways are necessary and sufficient to specify wing-specific responses to different signaling pathways. The obligate integration of selector and signaling protein inputs on cis-regulatory DNA may be a general mechanism by which selector proteins control extensive genetic regulatory networks during development.

Concentrations of steroid hormones in layers and biopsies of chelonian egg yolks.

The actions of circulating hormones, although relatively well understood for adults, are largely unknown for their developing embryos. Transfer of maternal hormones to the egg is known to occur in oviparous species, and recently the presence of hormonally heterogeneous yolk layers has been described in two avian species. To investigate the possibility of a similar phenomenon occurring in chelonian species, egg yolk layers were analyzed in the painted turtle (Chrysemys picta marginata) and the red-eared slider turtle (Trachemys scripta elegans), two species that exhibit temperature-dependent sex determination. There was a similar pattern of hormonally heterogeneous yolk layers in both species: concentrations of progesterone and testosterone were significantly higher in the external yolk layer while concentrations of 17beta-estradiol were significantly higher in the intermediate and internal layers. This pattern of hormone deposition concurs with previously published studies of plasma hormone profiles from females of temperate-zone turtle species. Yolks of freshly laid eggs were also sampled using a biopsy technique to examine the concordance of early yolk hormone concentrations and offspring sex. No relationship was found between yolk hormone concentrations and individual offspring sex. Previous work showing that maternally derived yolk estradiol concentrations are correlated with female-biased sex ratios was, however, replicated. These findings suggest that offspring sex is influenced, in part, by the maternal hormone environment.

Environmental sex determination in a reptile varies seasonally and with yolk hormones.

Most hypotheses that have been put forward in order to explain the persistence of environmental sex determination (ESD) in reptiles assume a relatively fixed association of sex with temperature-induced phenotype and no maternal influence on offspring sex. Here we demonstrate the association of maternally derived yolk hormone levels with the offspring sex ratio and describe two new aspects of temperature-dependent sex determination (TSD), i.e. seasonal variation in both thermal response and yolk steroid levels. Eggs from painted turtles (Chrysemys picta) were incubated at 28 degrees C. The hatchling sex ratio at 28 degrees C (i.e. the phenotypic reaction norm for sex at 28 degrees C) shifted seasonally from ca. 72% male to ca. 76% female. Yolk oestradiol (E2) increased seasonally while testosterone (T) decreased. The proportion of males in a clutch decreased as E2 levels increased and the E2:T ratio increased. These new findings are discussed in relation to heritability and adaptive explanations for the persistence of ESD in reptiles. Maternally derived yolk hormones may provide a mechanism for the seasonal shift in the sex ratio which in turn may help explain the persistence of ESD in reptiles. They may also explain those clutches of other reptiles with TSD that fail to yield only males at maximally masculinizing conditions.

The effect of isoniazid on BCG-induced toxicity in patients with superficial bladder cancer.

The use of bacillus Calmette-Guérin in the treatment of transitional cell cancer of the bladder has caused concern because of its associated adverse effects. We conducted a randomized prospective, double-blind, multicentre study to determine whether isoniazid prophylaxis could reduce BCG-induced toxicity without compromising its immunotherapeutic effects. Patients (n = 160) with histologically documented urothelial cancer (pTa-T1, pTis, G1-3) were treated with 6 weekly instillations of BCG Connaught strain, 81 mg, administered concomitantly with a 3-day course of isoniazid (300 mg o.d.) or placebo. Side-effects were recorded with each treatment and at follow-up. Of the patients treated with isoniazid, 19% remained free from side-effects, compared with 16% of the placebo group. Local side-effects confined to the bladder were significantly lower among those receiving isoniazid (35% vs. 48%, p < 0.01). Local side-effects together with systemic adverse effects such as fever, nausea or skin rash were experienced by 30% of patients in each arm. There were no differences in tumour recurrence between the two patient groups. Concomitant isoniazid reduces the local, but not the systemic side-effects of topically applied BCG without compromising the antitumour effect on superficial, transitional cell cancer of the bladder during a follow-up period that now exceeds 2 years.

Effects of testosterone on locomotor performance and growth in field-active northern fence lizards, Sceloporus undulatus hyacinthinus.

The role of steroids in locomotor performance and growth was examined in free-living lizards. Male northern fence lizards (Sceloporus undulatus hyacinthinus) with experimentally elevated plasma testosterone concentrations had greater sprint speed (+24%) and burst stamina (+17%) than sham-implanted males after 14-23 d in the field. This enhanced performance was associated with significant energetic costs, as the testosterone-implanted lizards had reduced growth rates, and, in a companion experiment, field-active testosterone-implanted lizards had smaller fat-body masses than controls after just 3-4 wk. These results suggest that, in addition to influencing a variety of behavioral and morphological traits, testosterone may play an important role in the regulation of locomotor performance. Also, natural levels of locomotor performance may be constrained, in part, by associated costs of elevated plasma testosterone concentrations.

The challenge hypothesis and seasonal changes in aggression and steroids in male northern fence lizards (Sceloporus undulatus hyacinthinus).

The challenge hypothesis has been very successful in explaining patterns of testosterone secretion in response to social stimuli in avian species. However, there have been few studies in nonavian vertebrates. We tested the challenge hypothesis in male northern fence lizards (Sceloporus undulatus hyacinthinus). These males are highly territorial and nonparental. Consequently, the challenge hypothesis predicts that plasma testosterone concentrations will be insensitive to aggressive interactions. Testosterone concentrations indeed were not significantly affected by either a short (3-15 min) simulated territorial intrusion ("challenge") in June or a longer (50-60 min) intrusion in July. Levels of corticosterone were elevated in challenged males in the long, but not the short, intrusion. Challenged males displayed significantly more intense territorial behaviors than did unchallenged control males. The intensity of territorial behavior changed significantly across the active season and was positively related to testosterone concentrations. Thus, while testosterone concentrations do not appear to be involved in rapid changes in aggressive behavior in the fence lizard, they probably are important in larger-scale behavioral changes throughout the season.

The planning process in occupational therapy: perceptions of adult rehabilitation patients.

OBJECTIVES: The purpose of this study was to learn about (a) adult physical rehabilitation patients' perceptions of their involvement in the treatment planning process (goal setting, treatment planning, outcome evaluation), (b) their valuation of occupational therapy, and (c) how they would describe their interpersonal relationships with their occupational therapists. METHOD: Fifteen subjects who had received occupational therapy were interviewed. The transcripts were independently and jointly reviewed by the authors to answer five research questions. RESULTS: Most of the subjects indicated that they had been involved in occupational therapy goal setting; treatment planning; and outcome evaluation, albeit this indication was weak. They also valued the occupational therapy services they received. Eight described positive interpersonal interactions with their therapists, and seven provided no information. CONCLUSION: Patients receiving occupational therapy services are involved in goal setting, treatment planning, and outcome evaluations; however, their involvement varies and can be difficult for them to identify and describe. Because of increasing societal emphasis on patient rights and participation (e.g., consumerism, health professions standards, health care accreditation criteria, health care legislation) and the likelihood that health care funding will be used for services linked to patient goals, occupational therapy practitioners could become more overt and systematic in involving patients in the planning process. Increasing patient involvement in planning may result in more individualized treatment and more effective use of health care dollars.

Comparison of the test-retest reliability of the Work Box using three administrative methods.

OBJECTIVE: The purpose of this study was to compare the test-retest reliability of three administrative methods of the Work Box: (a) the original instructions, (b) a revised version of the original instructions, and (c) another revised version that was based on suggestions made by authors of the first two versions of the instructions. METHOD: Sixty subjects without disabilities were randomly grouped so that 20 subjects were tested per administrative method. The assessment was administered to each subject on two occasions, with a 7-day to 14-day period between tests. Scores were recorded as time in seconds, and intraclass correlation coefficients (ICCs) were used to calculate the reliability. RESULTS: The ICCs for assembly, disassembly, and total scores were .589, .604, and .654, respectively, for the original instructions; .424, .572, and .545 for the revised instructions; and .781, .579, .717 for the second revised instructions. Reliability was found to be higher for men than for women and for subjects who claimed to have more rather than less experience in similar manual dexterity tasks. CONCLUSIONS: On the basis of the reliability of each administrative method and comments made by subjects about their understanding of the instructions, the second revised version of the instructions is recommended as the standard method. The results also indicate that the assessment is most appropriate for a population of men with manual dexterity experience. With further standardization, the Work Box could be a valuable assessment tool for therapists working in industrial rehabilitation settings.

Amlodipine overdose.

OBJECTIVE: To report a nonfatal intentional overdose of amlodipine. CASE SUMMARY: A 42-year-old woman with a history of hypertension reported ingesting 50-100 mg amlodipine besylate and at least 40 ounces of beer in a suicide attempt. The patient's symptoms were mild; BP ranged from 79/50 to 113/76 mm Hg and HR from 92 to 129 beats/min (sinus tachycardia). Laboratory studies revealed normoglycemia, mild metabolic acidosis, mild hypocalcemia, blood ethanol concentration of 263 mmol/L, and a serum amlodipine concentration of 88 ng/mL (normal 3-11) 2.5 hours after ingestion. Therapy included activated charcoal, whole bowel irrigation, and intravenous NaCl 0.9%. After receiving 1.5 L of NaCl 0.9%, the patient developed signs of mild pulmonary edema that resolved over several hours without intervention. A serum amlodipine concentration obtained 35 hours later was 79 mg/mL. The patient was discharged on day 2 in good condition. DISCUSSION: In this case, an amlodipine overdose was associated with sustained hypotension and sinus tachycardia, as well as transient pulmonary edema following relatively low-volume fluid replacement. A previously published report described an amlodipine overdose that was fatal due to refractory hypotension and was complicated by concomitant oxazepam overdose. CONCLUSIONS: Amlodipine overdose produces prolonged hemodynamic effects and may lead to pulmonary edema. Due to a long elimination half-life and delayed onset of effects, patients with amlodipine overdose should receive aggressive decontamination therapy and may require extended clinical monitoring and supportive care if they are hemodynamically unstable.

Analysis of Hox gene expression in the chick limb bud.

The vertebrate Hox genes have been shown to be important for patterning the primary and secondary axes of the developing vertebrate embryo. The function of these genes along the primary axis of the embryo has been generally interpreted in the context of positional specification and homeotic transformation of axial structures. The way in which these genes are expressed and function during the development of the secondary axes, particularly the limb, is less clear. In order to provide a reference for understanding the role of the Hox genes in limb patterning, we isolated clones of 23 Hox genes expressed during limb development, characterized their expression patterns and analyzed their regulation by the signalling centers which pattern the limb. The expression patterns of the Abd-B-related Hoxa and Hoxd genes have previously been partially characterized; however, our study reveals that these genes are expressed in patterns more dynamic and complex than generally appreciated, only transiently approximating simple, concentric, nested domains. Detailed analysis of these patterns suggests that the expression of each of the Hoxa and Hoxd genes is regulated in up to three independent phases. Each of these phases appears to be associated with the specification and patterning of one of the proximodistal segments of the limb (upper arm, lower arm and hand). Interestingly, in the last of these phases, the expression of the Hoxd genes violates the general rule of spatial and temporal colinearity of Hox gene expression with gene order along the chromosome. In contrast to the Abd-B-related Hoxa and Hoxd genes, which are expressed in both the fore and hind limbs, different sets of Hoxc genes are expressed in the two limbs. There is a correlation between the relative position of these genes along the chromosome and the axial level of the limb bud in which they are expressed. The more 3' genes are expressed in the fore limb bud while the 5' genes are expressed in the hind limb bud; intermediate genes are transcribed in both limbs. However, there is no clear correlation between the relative position of the genes along the chromosome and their expression domains within the limb. With the exception of Hoxc-11, which is transcribed in a posterior portion of the hind limb, Hoxc gene expression is restricted to the anterior/proximal portion of the limb bud. Importantly, comparison of the distributions of Hoxc-6 RNA and protein products reveals posttranscriptional regulation of this gene, suggesting that caution must be exercised in interpreting the functional significance of the RNA distribution of any of the vertebrate Hox genes. To understand the genesis of the complex patterns of Hox gene expression in the limb bud, we examined the propagation of Hox gene expression relative to cell proliferation. We find that shifts in Hox gene expression cannot be attributed to passive expansion due to cell proliferation. Rather, phase-specific Hox gene expression patterns appear to result from a context-dependent response of the limb mesoderm to Sonic hedgehog. Sonic hedgehog (the patterning signal from the Zone of Polarizing Activity) is known to be able to activate Hoxd gene expression in the limb. Although we find that Sonic hedgehog is capable of initiating and polarizing Hoxd gene expression during both of the latter two phases of Hox gene expression, the specific patterns induced are not determined by the signal, but depend upon the temporal context of the mesoderm receiving the signal. Misexpression of Sonic hedgehog also reveals that Hoxb-9, which is normally excluded from the posterior mesenchyme of the leg, is negatively regulated by Sonic hedgehog and that Hoxc-11, which is expressed in the posterior portion of the leg, is not affected by Sonic hedgehog and hence is not required to pattern the skeletal elements of the lower leg.

Sonic hedgehog regulates patterning in early embryos.

Recently, a new family of genes, homologues of the Drosophila segment polarity gene hedgehog, has been cloned in vertebrates. One of them, Sonic hedgehog, is expressed in tissues that are known to be inductive centres for patterning early embryos, implicating Sonic hedgehog as an important signal in development. Functional experiments have demonstrated that Sonic hedgehog acts as a signalling molecule in patterning the anterior-posterior axis of the limb. By misexpression of Sonic hedgehog we show that Sonic hedgehog induces expression of Hoxd genes, known to be involved in patterning of the anterior-posterior axis of the limb, and Bmp-2, which might act as a secondary signal. We also demonstrate that Sonic hedgehog is not sufficient for these inductions. In fact, a signal from the mesoderm, Sonic hedgehog, and a signal from the ectoderm, Fgf-4, are required for the induction of Hoxd genes and Bmp-2.

Normative data for the Work BOXTM: females ages 20-49.

The purpose of this project was to continue the development of the Work boxTM following three studies to standardize instructions and determine test-retest reliability. Normative data were collected from 118 non-disabled female subjects between the ages of 20 and 49 years. Means, standard deviations, and ranges of performance for 5-year-age intervals were calculated and reported for assembly time, disassembly time, and total test time. Analysis of the data indicates a minor, though not significant, decline in test performance with increasing age and great variability in completion times overall.

Sonic hedgehog is an endodermal signal inducing Bmp-4 and Hox genes during induction and regionalization of the chick hindgut.

Reciprocal inductive signals between the endoderm and mesoderm are critical to vertebrate gut development. Sonic hedgehog encodes a secreted protein known to act as an inductive signal in several regions of the developing embryo. In this report, we provide evidence to support the role of Sonic hedgehog and its target genes Bmp-4 and the Abd-B-related Hox genes in the induction and patterning the chick hindgut. Sonic is expressed in the definitive endoderm at the earliest stage of chick gut formation. Immediately subjacent to Sonic expression in the caudal endoderm is undifferentiated mesoderm, later to become the visceral mesoderm of the hindgut. Genes expressed within this tissue include Bmp-4 (a TGF-beta relative implicated in proper growth of visceral mesoderm) and members of the Abd-B class of Hox genes (known regulators of pattern in many aspects of development). Using virally mediated misexpression, we show that Sonic hedgehog is sufficient to induce ectopic expression of Bmp-4 and specific Hoxd genes within the mesoderm. Sonic therefore appears to act as a signal in an epithelial-mesenchymal interaction in the earliest stages of chick hindgut formation. Gut pattern is evidenced later in gut morphogenesis with the presence of anatomic boundaries reflecting phenotypically and physiologically distinct regions. The expression pattern of the Abd-b-like Hox genes remains restricted in the hindgut and these Hox expression domains reflect gut morphologic boundaries. This finding strongly supports a role for these genes in determining the adult gut phenotype. Our results provide the basis for a model to describe molecular controls of early vertebrate hindgut development and patterning. Expression of homologous genes in Drosophila suggest that aspects of gut morphogenesis may be regulated by similar inductive networks in the two organisms.

Involvement of adult rehabilitation patients in setting occupational therapy goals.

OBJECTIVE: This preliminary study was designed to determine whether occupational therapists involve patients and their families in a goal-setting process and, if so, to identify the methods used. METHOD: Thirty registered occupational therapists practicing in adult physical rehabilitation settings were audiotaped during an initial evaluation. Researchers reviewed corresponding documentation and interviewed each subject. Twenty-three patient and family involvement criteria were generated from standards developed by accreditation commissions and health care professions. RESULTS: Data revealed that although subjects did involve patients and families in a goal-setting process, a number of criteria were not attempted, thus much potential for involvement was unrealized. Subjects with scores above and below one standard deviation from the mean were identified to determine which patient participation criteria had the highest discrepancies. Discrepancies included (a) verbal preparation of the patient and family for initial and ongoing treatment, purposes and procedures of evaluation and treatment, and potential outcomes of treatment, (b) attempts to elicit the patient's concerns, and (c) collaboration with the patient to establish treatment goals. CONCLUSION: Factors that might have influenced subjects' use of a patient participation approach included the application of a specific theory or technique, time constraints, patient's age, and assumptions about the patient's cognitive status.

Hox genes and the evolution of vertebrate axial morphology.

A common form of evolutionary variation between vertebrate taxa is the different numbers of segments that contribute to various regions of the anterior-posterior axis; cervical vertebrae, thoracic vertebrae, etc. The term 'transposition' is used to describe this phenomenon. Genetic experiments with homeotic genes in mice have demonstrated that Hox genes are in part responsible for the specification of segmental identity along the anterior-posterior axis, and it has been proposed that an axial Hox code determines the morphology of individual vertebrae (Kessel, M. and Gruss, P. (1990) Science 249, 347-379). This paper presents a comparative study of the developmental patterns of homeobox gene expression and developmental morphology between animals that have homologous regulatory genes but different morphologies. The axial expression boundaries of 23 Hox genes were examined in the paraxial mesoderm of chick, and 16 in mouse embryos by in situ hybridization and immunolocalization techniques. Hox gene anterior expression boundaries were found to be transposed in concert with morphological boundaries. This data contributes a mechanistic level to the assumed homology of these regions in vertebrates. The recognition of mechanistic homology supports the historical homology of basic patterning mechanisms between all organisms that share these genes.