Shh promotes direct interactions between epidermal cells and osteoblast progenitors to shape regenerated zebrafish bone.

Zebrafish innately regenerate amputated fins by mechanisms that expand and precisely position injury-induced progenitor cells to re-form tissue of the original size and pattern. For example, cell signaling networks direct osteoblast progenitors (pObs) to rebuild thin cylindrical bony rays with a stereotypical branched morphology. Hedgehog/Smoothened (Hh/Smo) signaling has been variably proposed to stimulate overall fin regenerative outgrowth or promote ray branching. Using a photoconvertible patched2 reporter, we resolve active Hh/Smo output to a narrow distal regenerate zone comprising pObs and adjacent motile basal epidermal cells. This Hh/Smo activity is driven by epidermal Sonic hedgehog a (Shha) rather than Ob-derived Indian hedgehog a (Ihha), which nevertheless functions atypically to support bone maturation. Using BMS-833923, a uniquely effective Smo inhibitor, and high-resolution imaging, we show that Shha/Smo is functionally dedicated to ray branching during fin regeneration. Hh/Smo activation enables transiently divided clusters of Shha-expressing epidermis to escort pObs into similarly split groups. This co-movement likely depends on epidermal cellular protrusions that directly contact pObs only where an otherwise occluding basement membrane remains incompletely assembled. Progressively separated pObs pools then continue regenerating independently to collectively re-form a now branched skeletal structure.

Quality of early parent input predicts child vocabulary 3 years later.

Children vary greatly in the number of words they know when they enter school, a major factor influencing subsequent school and workplace success. This variability is partially explained by the differential quantity of parental speech to preschoolers. However, the contexts in which young learners hear new words are also likely to vary in referential transparency; that is, in how clearly word meaning can be inferred from the immediate extralinguistic context, an aspect of input quality. To examine this aspect, we asked 218 adult participants to guess 50 parents' words from (muted) videos of their interactions with their 14- to 18-mo-old children. We found systematic differences in how easily individual parents' words could be identified purely from this socio-visual context. Differences in this kind of input quality correlated with the size of the children's vocabulary 3 y later, even after controlling for differences in input quantity. Although input quantity differed as a function of socioeconomic status, input quality (as here measured) did not, suggesting that the quality of nonverbal cues to word meaning that parents offer to their children is an individual matter, widely distributed across the population of parents.

Using retest-adjusted correlations as indicators of the semantic similarity of items.

Determining whether different items provide the same information or mean the same thing within a population is a central concern when determining whether different scales or constructs are overlapping or redundant. In the present study, we suggest that retest-adjusted correlations provide a valuable means of adjusting for item-level unreliability. More exactly, we suggest dividing the estimated correlation between items X and Y measured over measurement interval |d| by the average retest correlations of the items over the same measurement interval. For instance, if we correlate scores from items X and Y measured 1 week apart, their retest-adjusted correlation is estimated by using their 1-week retest correlations. Using data from four inventories, we provide evidence that retest-adjusted correlations are significantly better predictors of whether two items are consensually regarded as "meaning the same thing" by judges than raw-score correlations. The results may provide the first empirical evidence that Spearman's (1904, 1910) suggested reliability adjustment do-in certain (perhaps very constrained!) circumstances-improve upon raw-score correlations as indicators of the informational or semantic equivalence of different tests. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Australian Gonococcal Surveillance Programme Annual Report, 2021.

The Australian Gonococcal Surveillance Programme, established in 1981, has continuously monitored antimicrobial resistance in Neisseria gonorrhoeae for more than 40 years. In 2021, a total of 6,254 isolates from patients in the public and private sectors, in all jurisdictions, were tested for in vitro antimicrobial susceptibility by standardised methods. The current treatment recommendation for gonorrhoea, for the majority of Australia, continues to be dual therapy with ceftriaxone and azithromycin. In 2021, of isolates tested, 0.9% were reported nationally with decreased susceptibility (DS) to ceftriaxone (minimum inhibitory concentration [MIC] value ≥ 0.06 mg/L). There was one isolate from non-remote Western Australia that was resistant to ceftriaxone (MIC value ≥ 0.25 mg/L). Resistance to azithromycin (MIC value ≥ 1.0 mg/L) was reported nationally in 4.7% of N. gonorrhoeae isolates. This is increased from that reported in 2020 (3.9%) but similar to the percentage reported in 2019 (4.6%). Isolates with high-level resistance to azithromycin (MIC value ≥ 256 mg/L) are identified sporadically in Australia; none were reported in 2021. In 2021, penicillin resistance was found in 38% of gonococcal isolates nationally, and ciprofloxacin resistance in 53%; however, there is considerable variation by jurisdiction. In some remote settings, penicillin resistance remains low; in these settings, penicillin continues to be recommended as part of an empiric therapy strategy. In 2021, in remote Northern Territory, one penicillin-resistant isolate was reported, and in remote Western Australia 2/83 of gonococcal isolates (2.4 %) were penicillin resistant. There were two ciprofloxacin-resistant isolates reported from remote Northern Territory; ciprofloxacin resistance rates remain comparatively low in remote Western Australia (3/83; 3.6 %).

Australian Gonococcal Surveillance Programme Annual Report, 2020.

ABSTRACT: The Australian Gonococcal Surveillance Programme (AGSP), established in 1981, has continuously monitored antimicrobial resistance in clinical isolates of Neisseria gonorrhoeae for more than 40 years. In 2020, a total of 7,222 clinical isolates of gonococci from patients in the public and private sectors, in all jurisdictions, were tested for in vitro antimicrobial susceptibility by standardised methods. Current treatment recommendations for gonorrhoea, for the majority of Australia, continues to be dual therapy with ceftriaxone and azithromycin. In 2020, decreased susceptibility (DS) to ceftriaxone (minimum inhibitory concentration [MIC] value ≥ 0.06 mg/L) was found nationally in 0.9% of isolates. There was one isolate, reported from Victoria in 2020, that was resistant to ceftriaxone (MIC value ≥ 0.25 mg/L). Resistance to azithromycin (MIC value ≥ 1.0 mg/L) was found nationally in 3.9% of N. gonorrhoeae isolates, continuing a downward trend observed and reported since 2017. Isolates with high-level resistance to azithromycin (MIC value ≥ 256 mg/L) are identified sporadically in Australia; in 2020, there was one such isolate reported in Queensland. In 2020, penicillin resistance was found in 27% of gonococcal isolates nationally, and ciprofloxacin resistance in 36%; however, there is considerable variation by jurisdiction. In some remote settings, penicillin resistance remains low, and this drug continues to be recommended as part of an empiric therapy strategy. In 2020, in remote Northern Territory, no penicillin resistance was reported, and in remote Western Australia 5/116 of gonococcal isolates (4.3%) were penicillin resistant. There was one ciprofloxacin-resistant isolate reported from remote Northern Territory, and ciprofloxacin resistance rates remain comparatively low in remote Western Australia (4/116; 3.4%).

Australian Gonococcal Surveillance Programme Annual Report, 2020.

Abstract: The Australian Gonococcal Surveillance Programme (AGSP), established in 1981, has continuously monitored antimicrobial resistance in clinical isolates of Neisseria gonorrhoeae for more than 40 years. In 2020, a total of 7,219 clinical isolates of gonococci from patients in the public and private sectors, in all jurisdictions, were tested for in vitro antimicrobial susceptibility by standardised methods. Current treatment recommendations for gonorrhoea, for the majority of Australia, continues to be dual therapy with ceftriaxone and azithromycin. In 2020, decreased susceptibility (DS) to ceftriaxone (minimum inhibitory concentration [MIC] value ≥ 0.06 mg/L) was found nationally in 0.9% of isolates. There was one isolate, reported from Victoria in 2020, that was resistant to ceftriaxone (MIC value ≥ 0.25 mg/L). Resistance to azithromycin (MIC value ≥ 1.0 mg/L) was found nationally in 3.9% of N. gonorrhoeae isolates, continuing a downward trend observed and reported since 2017. Isolates with high-level resistance to azithromycin (MIC value ≥ 256 mg/L) are identified sporadically in Australia; in 2020, there was one such isolate reported in Queensland. In 2020, penicillin resistance was found in 27% of gonococcal isolates nationally, and ciprofloxacin resistance in 36%; however, there is considerable variation by jurisdiction. In some remote settings, penicillin resistance remains low, and this drug continues to be recommended as part of an empiric therapy strategy. In 2020, in remote Northern Territory, no penicillin resistance was reported, and in remote Western Australia 5/116 of gonococcal isolates (4.3%) were penicillin resistant. There was one ciprofloxacin-resistant isolate reported from remote Northern Territory, and ciprofloxacin resistance rates remain comparatively low in remote Western Australia (4/116; 3.4%).

Is gentamicin a viable therapeutic option for treating resistant Neisseria gonorrhoeae in New South Wales?

ABSTRACT: The key issues with Neisseria gonorrhoeae infections, in Australia and elsewhere, are coincident increases in disease rates and in antimicrobial resistance (AMR), although these factors have not been shown to be correlated. Despite advances in diagnosis, control of this disease remains elusive, and incidence in Australia continues to increase. Of the Australian jurisdictions, New South Wales (NSW) has the highest N. gonorrhoeae notifications, and over the five-year period 2015-2019, notifications in NSW have increased above the national average (by 116% versus 85%, respectively). Gonococcal disease control is reliant on effective antibiotic regimens. However, escalating AMR in N. gonorrhoeae is a global health priority, as the collateral injury of untreated infections has substantive impacts on sexual and newborn health. Currently, our first-line therapy for gonorrhoea is also our last line, with no ideal alternative identified. Despite some limitations, gentamicin is licensed and readily available in Australia, and is proposed for treatment of resistant N. gonorrhoeae in national guidelines; however, supportive published microbiological data are lacking. Analysis of gonococcal resistance patterns within Australia for the period 1991-2019, including 35,000 clinical isolates from NSW, illustrates the establishment and spread of population-level resistance to all contemporaneous therapies. An analysis of gentamicin susceptibility on 2,768 N. gonorrhoeae clinical isolates from NSW, for the period 2015-2020, demonstrates that the median minimum inhibitory concentration (MIC) for gentamicin in NSW has remained low, at 4.0 mg/L, and resistance was not detected in any isolate. There has been no demonstration of MIC drift over time (p = 0.91, Kruskal-Wallis test), nor differences in MIC distributions according to patients' sex or site of specimen collection. This is the first large-scale evaluation of gentamicin susceptibility in N. gonorrhoeae in Australia. No gentamicin resistance was detected in clinical isolates, 2015-2020, hence this is likely to be an available treatment option for resistant gonococcal infections in NSW.

Successful treatment of invasive carbapenemase-producing Enterobacteriaceae infections in children using carbapenem-aminoglycoside combination therapy: A case series.

Multidrug-resistant infections present a treatment challenge for pediatric clinicians and these infections have been associated with increased morbidity and mortality. There are very limited published data to support safe and effective treatment regimens for carbapenemase-producing Enterobacteriaceae (CPE) infections, particularly in children. We report the successful treatment of three children with invasive CPE infections using a combination of extended-infusion meropenem and amikacin.

Bacterial Ocular Surveillance System (BOSS) Sydney, Australia 2017-2018.

ABSTRACT: This study investigated antimicrobial resistance (AMR) profiles from a cohort of patients with bacterial keratitis treated at Sydney Eye Hospital, 1 January 2017 - 31 December 2018. These AMR profiles were analysed in the context of the current Australian empiric regimens for topical therapy: ciprofloxacin/ofloxacin monotherapy versus combination therapy of cefalotin/cephazolin plus gentamicin. At our Centre, combinations of (i) chloramphenicol plus gentamicin and (ii) chloramphenicol plus ciprofloxacin are alternatively used, so were also analysed. Three hundred and seventy-four isolates were cultured prospectively: 280/374 (75%) were gram positive, and 94/374 (25%) were gram negative. Coagulase-negative staphylococci comprised 173/374 (46%). Isolates included Staphylococcus aureus (n = 43/374) 11%; Streptococcus pneumoniae (n = 14/374) 3.7%; and Pseudomonas aeruginosa (n = 50/374) 13%. Statistical comparison was performed. There was no significant difference between cover provided either of the current Australian recommendations: ciprofloxacin/ofloxacin vs cefalotin/cephazolin plus gentamicin (5.3% vs 4.8%, respectively; p = 0.655). However, the combination of chloramphenicol plus an anti-pseudomonal agent (ciprofloxacin/ofloxacin or gentamicin) had significantly improved cover. Chloramphenicol plus gentamicin was superior to ciprofloxacin/ofloxacin (1.9% vs 5.3% resistance respectively; p = 0.007), and cefalotin/cephazolin plus gentamicin (1.9% vs 4.8%; p = 0.005). Chloramphenicol plus ciprofloxacin was superior to ciprofloxacin/ofloxacin monotherapy (1.3% vs 5.3%; p ≤ 0.001), and to cefalotin/cephazolin plus gentamicin (1.3% vs 4.8%; p = 0.003). Chloramphenicol plus gentamicin versus chloramphenicol plus ciprofloxacin/ofloxacin were equivalent (p = 0.48). There was no demonstrated in vitro superiority of either the current empiric antibiotic regimens. For our setting, for bacterial keratitis, chloramphenicol in combination offered superior in vitro cover. Broadened surveillance for ocular AMR is urgently needed across jurisdictions.

Australian Gonococcal Surveillance Programme Annual Report, 2019.

The Australian Gonococcal Surveillance Programme (AGSP) has continuously monitored antimicrobial resistance in clinical isolates of Neisseria gonorrhoeae since 1981. In 2019, a total of 9,668 clinical isolates of gonococci from the public and private sector in all jurisdictions were tested for in vitro antimicrobial susceptibility by standardised methods. The current treatment recommendation for gonorrhoea, for the majority of Australia, continues to be dual therapy with ceftriaxone and azithromycin. Decreased susceptibility (DS) to ceftriaxone (minimum inhibitory concentration [MIC] value ≥ 0.06 mg/L) was found nationally in 1.3% of isolates. Five N. gonorrhoeae clinical isolates were ceftriaxone-resistant (MIC value ≥ 0.25 mg/L), and therefore also resistant to penicillin; all were resistant to ciprofloxacin but susceptible to azithromycin. These isolates were reported from Victoria (3), non-remote Western Australia (1) and New South Wales (1). Resistance to azithromycin (MIC value ≥ 1.0 mg/L) was found nationally in 4.6% of N. gonorrhoeae isolates, continuing a downward trend observed and reported since 2017. Isolates with high-level resistance to azithromycin (MIC value ≥ 256 mg/L) continue to be reported sporadically in Australia, with eight detected in 2019: two each from New South Wales, Queensland, and Victoria, and one each from Tasmania and non-remote Western Australia. In 2019, in Australia, 2,136 gonococcal isolates (22.1%) were penicillin resistant; however, there remains considerable variation by jurisdiction, and in some remote settings there is little resistance and this drug is recommended empiric therapy. In 2019, in the remote Northern Territory, no penicillin resistance was reported, however in remote Western Australia six out of 85 isolates (7.1%) were penicillin resistant. There was no ciprofloxacin resistance reported from isolates tested from remote regions of the Northern Territory, and ciprofloxacin resistance rates remain comparatively low (7/85; 8.2%) in remote Western Australia.

What predicts who we approach for social support? Tests of the attachment figure and strong ties hypotheses.

Before people seek support for an issue, they must choose whom in their support network to approach. Two prominent supporter-selection hypotheses are the attachment figure hypothesis and the strong ties hypothesis, housed in psychology and sociology, respectively. People are expected to have a special preference for attachment figures and also for strong ties and to seek them more frequently than others. Despite the widespread acceptance of these hypotheses, neither has ever been tested, we argue, with the most appropriate methods for their claims. Moreover, no one has ever tested whether the 2 theories might not be independent, that is, whether one might subsume the other. To properly test the theories, one requires intranetwork, enacted support-seeking data, and the theories must be modeled not just separately but also simultaneously. The present article reports 3 such studies. In Studies 1 and 3, a sample of adults reported their supporter-selection decisions for a single stressful event, and in Study 2, a sample of emerging adults reported their supporter-selection decisions for a period of 2 weeks. Evidence showed that each theory uniquely predicted supporter-selection decisions. For each theory the data revealed both expected and unexpected findings. Attachment figures were selectively sought for support, but this preference did not get stronger as issues became more severe. Stronger ties were selected more often than weaker ties; however, the strong tie effect emerged as 2 independent effects rather than one (closeness and interaction frequency). Taken together, the studies supported both theories, but also suggest the need for further theoretical development. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Estimating the reliability of emotion measures over very short intervals: The utility of within-session retest correlations.

Short measures are commonly used when conducting research involving emotions. However, obtaining appropriate estimates of reliability for short measures is traditionally problematic and is a reoccurring concern in emotion research. To address this issue, we compare the within-session test-retest and factor analysis methods for estimating the reliability of items in the Positive and Negative Affect Schedule-Expanded Form. Results indicate that within-session test-retest (rXX(d)) estimates outperform the factor analysis method by demonstrating stronger relationships with item properties relevant to reliability and validity-related criteria. In addition, rXX(d) estimates appropriately generalize across samples with various instruction stems and prevent corrections for attenuation greater than 1.00. Therefore, we encourage researchers to use the corresponding average item-level rXX(d) estimates reported here to correct for attenuation when examining single items from the Positive and Negative Affect Schedule-Expanded Form if a test-retest design is not feasible. (PsycINFO Database Record

Cardiovascular Interactions between Fibroblast Growth Factor-23 and Angiotensin II.

Both the activation of the renin angiotensin aldosterone system (RAAS) and elevations of circulating Fibroblast Growth Factor-23 (FGF-23) have been implicated in the pathogenesis of left ventricular hypertrophy (LVH) in chronic kidney disease. To investigate potential cross-talk between RAAS and FGF-23, we administered angiotensin II (Ang II) to wild-type rodents and the Hyp mouse model of excess FGF-23. Ang II administration for four weeks to wild-type rodents resulted in significant increases in systolic blood pressure and LVH. Unexpectedly, FGF-23 circulating levels were increased by 1.5-1.7 fold in Ang II treated animals. In addition, Ang II treatment increased expression of FGF-23 message levels in bone, the predominant tissue for FGF-23 production, and induced expression of FGF-23 and its co-receptor α-Klotho in the heart, which normally does not express FGF-23 or α-Klotho in physiologically relevant levels. Hyp mice with elevated FGF-23 exhibited increased blood pressure and LVH at baseline. Ang II administration to Hyp mice resulted further increments in blood pressure and left ventricular hypertrophy, consistent with additive cardiovascular effects. These findings suggest that FGF-23 may participate in unexpected systemic and paracrine networks regulating hemodynamic and myocardial responses.

Perceiving referential intent: Dynamics of reference in natural parent-child interactions.

Two studies are presented which examined the temporal dynamics of the social-attentive behaviors that co-occur with referent identification during natural parent-child interactions in the home. Study 1 focused on 6.2 h of videos of 56 parents interacting during everyday activities with their 14-18 month-olds, during which parents uttered common nouns as parts of spontaneously occurring utterances. Trained coders recorded, on a second-by-second basis, parent and child attentional behaviors relevant to reference in the period (40 s) immediately surrounding parental naming. The referential transparency of each interaction was independently assessed by having naïve adult participants guess what word the parent had uttered in these video segments, but with the audio turned off, forcing them to use only non-linguistic evidence available in the ongoing stream of events. We found a great deal of ambiguity in the input along with a few potent moments of word-referent transparency; these transparent moments have a particular temporal signature with respect to parent and child attentive behavior: it was the object's appearance and/or the fact that it captured parent/child attention at the moment the word was uttered, not the presence of the object throughout the video, that predicted observers' accuracy. Study 2 experimentally investigated the precision of the timing relation, and whether it has an effect on observer accuracy, by disrupting the timing between when the word was uttered and the behaviors present in the videos as they were originally recorded. Disrupting timing by only ±1 to 2 s reduced participant confidence and significantly decreased their accuracy in word identification. The results enhance an expanding literature on how dyadic attentional factors can influence early vocabulary growth. By hypothesis, this kind of time-sensitive data-selection process operates as a filter on input, removing many extraneous and ill-supported word-meaning hypotheses from consideration during children's early vocabulary learning.

Sequential and opposing activities of Wnt and BMP coordinate zebrafish bone regeneration.

Zebrafish fully regenerate lost bone, including after fin amputation, through a process mediated by dedifferentiated, lineage-restricted osteoblasts. Mechanisms controlling the osteoblast regenerative program from its initiation through reossification are poorly understood. We show that fin amputation induces a Wnt/ß-catenin-dependent epithelial to mesenchymal transformation (EMT) of osteoblasts in order to generate proliferative Runx2(+) preosteoblasts. Localized Wnt/ß-catenin signaling maintains this progenitor population toward the distal tip of the regenerative blastema. As they become proximally displaced, preosteoblasts upregulate sp7 and subsequently mature into re-epithelialized Runx2(-)/sp7(+) osteoblasts that extend preexisting bone. Autocrine bone morphogenetic protein (BMP) signaling promotes osteoblast differentiation by activating sp7 expression and counters Wnt by inducing Dickkopf-related Wnt antagonists. As such, opposing activities of Wnt and BMP coordinate the simultaneous demand for growth and differentiation during bone regeneration. This hierarchical signaling network model provides a conceptual framework for understanding innate bone repair and regeneration mechanisms and rationally designing regenerative therapeutics.