Mental health impacts of climate change and extreme weather events on mothers.

Background: The perinatal period is a time of increased vulnerability for perinatal mood and anxiety disorders (PMADs). Emotional trauma is a risk factor for PMAD development and is common among survivors of extreme weather events (EWEs), which are becoming more frequent and intense as the climate crisis progresses. EWE-related stress and anxiety have not been extensively studied in the perinatal population. However, the limited available data suggest a negative impact of EWE exposure on perinatal mental health, warranting further investigation and investment.Objective: To address this knowledge gap, we interviewed new Australian mothers to understand how EWEs affect the mental health of the perinatal population.Method: Australian mothers (18 years of age or older) with a baby under 12 months of age were recruited to participate in a single virtual focus group session (seven group sessions were run in total) and complete an anonymous survey. Participants were asked questions regarding their concerns about extreme weather and its impact, as well as their general maternal functioning. Maternal functioning, depression, and climate distress were measured via the survey.Results: The study sample comprised 31 Australian mothers (Mage = 31.74, SD = 4.86), predominantly located in Queensland. Findings from the focus groups suggested six key themes; however, of focus to this study are three themes related to maternal mental health: health and well-being, helplessness and avoidant coping, and resilience and adaptation. Predominant subthemes focused on trauma resulting from EWE exposure, economic and heat concerns, social isolation, hopelessness about the future, and feelings of resilience.Conclusions: The evidence linking adverse perinatal mental health outcomes with climate change and EWEs highlights the urgent need for interventions in this context to protect perinatal mental health and well-being. By acknowledging the traumatic impact of these experiences on mothers, this study supports advocacy for policies that specifically address this issue.

The extra consideration of navigating climatic events with children represented a complicating factor in addition to the demands of motherhood.Heat presented as a serious concern for participants, often as part of maintaining the balance between protecting their children's health and well-being and preserving their own mental health.Mothers simultaneously were disengaged from climate-related discussion or action and expressed feelings of helplessness in the face of the magnitude of climate change.

Are the Cytotoxic Properties of Conjugated Unsaturated Ketones Inactivated by Thiols?

The focus of this study was to examine whether the conversion of cytotoxic conjugated unsaturated ketones (or enones) into the corresponding thiol adducts leads to a reduction or abolition of cytotoxic potencies. A number of enones and related thiol adducts were evaluated against human HCT116 and HT29 colon cancer cells. Some 63% of the IC50 values are less than 10 µM and several compounds are more toxic than 5-FU. The thiol adducts are either more potent or are equipotent with the corresponding enones. A number of compounds are far more toxic to HCT116 and HT29 neoplasms than non-malignant CRL1790 cells leading to impressive Selectivity Index figures. An additional positive feature of these compounds is that they have favorable ADME properties.

Incidence, Mechanisms, and Characteristics of Injuries in Pole Dancers: A Prospective Cohort Study.

OBJECTIVE: Pole dancing is a challenging physical activity. Prospective injury studies in pole dancing are lacking. The aim of this study was to describe the incidence, mechanisms, and characteristics of injuries in pole dancers. METHODS: A total of 66 pole dancers from 41 studios across Australia were prospectively followed over 12 months. An intake questionnaire was administered including items on pole dancers' demographics and training characteristics. Exposure was assessed using a daily online training diary. Self-reported injury data were collected via an incident report form and subsequently coded using the Orchard Sports Injury Classification System. Injuries occurring during pole-specific and pole-related activities were included in the analyses. RESULTS: The sample included 63 females and 3 males, mean age 32.3 ± 8.9 years and mean pole training experience 3.5 ± 2.8 years. 25 of 66 participants completed the full study. The 1-year incidence of all new injuries was 8.95/1,000 exposure hours (95% CI 6.94 - 10.96), 7.65/1,000 hrs (95% CI 5.79 - 9.51) for pole-specific injuries and 1.29/1,000 hrs (95% CI 0.53 - 2.06) for pole-related injuries. A total of 103 injuries occurred, 62.1% of which were sudden onset and 37.9% gradual onset. Mechanism of onset included 54.4% acute and 45.6% repetitive in nature. Shoulder (20.4%) and thigh (11.7%, majority ham¬string) were the most reported anatomic injury sites. Non-contact mechanisms accounted for the majority of injuries (57.3%). The most reported primary contributor to injury onset at the shoulder were manoeuvres characterised by loaded internal humeral rotation (33.3%), and at the hamstring were manoeuvres and postures involving front splits (100.0%). CONCLUSION: The findings indicate that pole dancers are at high risk for injuries. Future research is needed to understand the biomechani¬cal demand of manoeuvres and training characteristics of pole dancing (e.g., workload and recovery) to guide the development of preventative interventions, particularly targeted toward the shoulder and hamstring.

Cytotoxic benzylidene hydrazides of terephthalic acid and related compounds.

The present investigation involved the synthesis of a number of novel benzylidene hydrazides as candidate cytotoxic agents. The preparation of these compounds from terephthalic acid and isophthalic acid proceeded satisfactorily. However, the reaction of phthalic acid hydrazide with various aryl aldehydes was unsuccessful in general. Some of the unexpected products were identified. The shapes and also the distances between the centers of the aryl rings designated B and C of three representative compounds 1b, 2b and 3b were determined. The compounds designated 1a-e, 2a-e and 3b were screened against human HCT116 and HT29 colon cancer cells as well as human CRL1790 non-malignant colon cells which revealed the tumor-selective toxicity displayed by these compounds.

A peer support intervention for first-time mothers: Feasibility and preliminary efficacy of the mummy buddy program.

BACKGROUND: The transition to motherhood, although joyous, can be highly stressful, and the availability of professional postpartum support for mothers is often limited. Peer volunteer support programs may offer a viable and cost-effective method to provide community-based support for new mothers. AIM: To determine the feasibility of a peer volunteer support program-The Mummy Buddy Program-in which experienced volunteer mothers are paired with, and trained to offer social support to, first-time mothers. METHODS: Using a single-group non-randomised feasibility trial, a total of 56 experienced mothers participated in the Mummy Buddy training program, which was focused on education and practical exercises relating to the provision of various forms of social support. Experienced mothers ('Mummy Buddies') were subsequently paired with expectant first-time mothers (n=47 pairs), and were encouraged to provide support until 24-weeks postpartum. FINDINGS: In terms of key feasibility considerations, 95.1% of Mummy Buddies felt that they were trained sufficiently to perform their role, and 85.8% of New Mothers were satisfied with the support provided by their Buddy. Analyses of preliminary efficacy (i.e., program outcomes) revealed that the first-time mothers maintained normal levels of stress and depressive symptomology, and possessed relatively strong maternal functioning, across the program duration. CONCLUSION: The Mummy Buddy Program appears to be a feasible and potentially valuable peer volunteer support program for first-time mothers. This study provides a foundation for program expansion and for work designed to examine program outcomes-for first-time mothers, Mummy Buddies, and entire family units-within a sufficiently-powered randomised controlled trial.

Establishment of tandem mass spectrometric fingerprint of novel antineoplastic curcumin analogues using electrospray ionization.

RATIONALE: Curcumin analogues are antineoplastic agents, designed based on the structure of the spice turmeric with structural modifications aiming at enhancing potency. The goal is to identify the common tandem mass spectrometric (MS/MS) behavior of 13 novel curcumin analogues. Such knowledge is critical for their biological assessment, including metabolite identification and pharmacokinetic evaluation. METHODS: Both detection of the protonated molecules [M + H](+) of the synthesized compounds and determination of their exact molecular masses were achieved with hybrid quadrupole orthogonal time-of-flight mass spectrometry (QqTOF-MS). Low-energy collision-induced dissociation (CID)-MS/MS analysis was performed using triple quadrupole linear ion trap mass spectrometry (QqLIT-MS). Both instruments were equipped with an electrospray ionization (ESI) source. MS(3) and neutral loss experiments were performed using QqLIT-MS to confirm the genesis of the observed product ions. RESULTS: Abundant [M + H](+) molecules were formed using the QqTOF-MS hybrid instrument with mass accuracies below 6 ppm. CID-MS/MS dissociation studies were centered on the piperidone ring of curcumin analogues; twelve common product ions have been identified from the fission of the various bonds within the piperidone moiety. There was a tendency for the formation of highly conjugated product ions, stabilized via resonance. The variety of the side-chain substituents at the nitrogen atom resulted in side-chain-specific product ions. CONCLUSIONS: The ESI-CID-MS/MS analysis of curcumin analogues revealed a common fragmentation behavior of all tested compounds, which gave diagnostic product ions identified for each molecule. The established MS/MS behavior will be applied to determine metabolic by-products of curcumin analogues as well as to develop targeted identification/quantification methods within biological extracts.

Young athletes' awareness and monitoring of anti-doping in daily life: Does motivation matter?

This study was a preliminarily investigation into the prevention of unintentional doping on the basis of self-determination theory (SDT). Specifically, we examined the relationship between athletes' motives for doping avoidance and their behavior when offered an unfamiliar food product. Participants were young Australian athletes (n = 410) that were offered a free lollipop prior to completing a questionnaire. It was noted whether participants refused to take or eat the lollipop and whether they read the ingredients of the lollipop. The questionnaire assessed autonomous and controlled forms of motivation, amotivation, doping intentions, and adherence regarding doping avoidance behaviors. The results showed that young athletes who adopted controlled reasons to avoid doping in sport (e.g., not getting caught) tended to report higher adherence to behaviors related to avoiding and monitoring banned substances, whereas those who adopted autonomous reasons (e.g., anti-doping being consistent with life goals) appeared to be more willing to read the ingredients of the provided food. The significant interaction effect between autonomous and controlled motivation indicated that autonomous motivation was more predictive to doping intention for athletes with low controlled motivation. It is concluded that SDT may help understand the motivational processes of the prevention of unintentional doping in sport.

Self-determined motivation in sport predicts anti-doping motivation and intention: a perspective from the trans-contextual model.

OBJECTIVES: Motivation in sport has been frequently identified as a key factor of young athletes' intention of doping in sport, but there has not been any attempt in scrutinizing the motivational mechanism involved. The present study applied the trans-contextual model of motivation to explain the relationship between motivation in a sport context and motivation and the social-cognitive factors (attitude, subjective norm, perceived behavioral control, and intention) from the theory of planned behavior (TPB) in an anti-doping context. DESIGN: A cross-sectional survey was conducted. METHODS: Questionnaire data was collected from 410 elite and sub-elite young athletes in Australia (Mean age [17.7±3.9 yr], 55.4% male, Years in sport [9.1±3.2]). We measured the key model variables of study in relation to sport motivation (Behavioral Regulation in Sport Questionnaire), and the motivation (adapted version of the Treatment Self-Regulation Questionnaire) and social cognitive patterns (the theory of planned behavior questionnaire) of doping avoidance. The data was analyzed by variance-based structural equation modeling with bootstrapping of 999 replications. RESULTS: The goodness-of-fit of the hypothesized model was acceptable. The bootstrapped parameter estimates revealed that autonomous motivation and amotivation in sport were positively associated with the corresponding types of motivation for the avoidance of doping. Autonomous motivation, subjective norm, and perceived behavioral control in doping avoidance fully mediated the relationship between autonomous motivation in sport and intention for doping avoidance. CONCLUSIONS: The findings support the tenets of the trans-contextual model, and explain how motivation in sport is related to athletes' motivation and intention with respect to anti-doping behaviors.

The unexpected formation of [M - H]+ species during MALDI and dopant-free APPI MS analysis of novel antineoplastic curcumin analogues.

Unusual ionization behavior was observed with novel antineoplastic curcumin analogues during the positive ion mode of matrix-assisted laser desorption ionization (MALDI) and dopant-free atmospheric pressure photoionization (APPI). The tested compounds produced an unusual significant peak designated as [M - H](+) ion along with the expected [M + H](+) species. In contrast, electrospray ionization, atmospheric pressure chemical ionization and the dopant-mediated APPI (dopant-APPI) showed only the expected [M + H](+) peak. The [M - H](+) ion was detected with all evaluated curcumin analogues including phosphoramidates, secondary amines, amides and mixed amines/amides. Our experiments revealed that photon energy triggers the ionization of the curcumin analogues even in the absence of any ionization enhancer such as matrix, solvent or dopant. The possible mechanisms for the formation of both [M - H](+) and [M + H](+) ions are discussed in this paper. In particular, three proposed mechanisms for the formation of [M - H](+) were evaluated. The first mechanism involves the loss of H2 from the protonated [M + H](+) species. The other two mechanisms include hydrogen transfer from the analyte radical cation or hydride abstraction from the neutral analyte molecule.

Inhibition of protein N-myristoylation: a therapeutic protocol in developing anticancer agents.

N-myristoyltransferase (NMT) is an essential eukaryotic enzyme which catalyzes the transfer of the myristoyl group to the terminal glycine residue of a number of proteins including those involved in signal transduction and apoptotic pathways. Myristoylation is crucial for the cellular proliferation process and is required for the growth and development in a number of organisms including many human pathogens and viruses. Targeting the myristoylation process thus has emerged as a novel therapeutic strategy for anticancer drug design. The expression/activity of NMT is considerably elevated in a number of cancers originating in the colon, stomach, gallbladder, brain and breast and attenuation of NMT levels has been shown to induce apoptosis in cancerous cell lines and reduce tumor volume in murine xenograft models for cancer. A focus of current therapeutic interventions in novel cancer treatments is therefore directed at developing specific NMT inhibitors. The inhibition of the myristoyl lipidation process with respect to cancer drug development lies in the fact that many proteins involved in oncogenesis such as src and various kinases require myristoylation to perform their cellular functions. Inhibiting NMT functions to control malignancy is a novel approach in the area of anticancer drug design and there are rapidly expanding discoveries of synthetic NMT inhibitors as potential chemotherapeutic agents to be employed in the warfare against cancer. The current review focuses on developments of various chemical NMT inhibitors with potential roles as anticancer agents.

2-[4-(4-Methoxyphenylcarbonyloxy)benzylidene]-6-dimethylaminomethyl cyclohexanone hydrochloride: a Mannich base which inhibits the growth of some drug-resistant strains of Mycobacterium tuberculosis.

2-[4-(4-Methoxyphenylcarbonyloxy)benzylidene]-6-dime-thylaminomethyl cyclohexanone hydrochloride 1 has a MIC value of 0.78 microg/mL towards Mycobacterium tuberculosis H37Rv and displays similar or identical MIC figures towards various drug-resistant strains of this microorganism. The enone 1 along with a partial structure 2-dimethylaminomethylcyclohexanone hydrochloride 3 affected respiration in isolated rat liver mitochondria differently which may contribute to the variation in toxicity to both normal cells and M. tuberculosis.

1,5-diaryl-3-oxo-1,4-pentadienes: a case for antineoplastics with multiple targets.

A number of organic molecules which contain the 1,5-diaryl-3-oxo-1,4-pentadienyl group, referred to hereafter as the dienone moiety, have antineoplastic properties. Emphasis is made on the attachment of this structural moiety to several molecular scaffolds, namely piperidines, N-acylpiperidines, cycloalkanes and 3,4-dihydro-1H-napthalenes. Many of these compounds are potent cytotoxins having micromolar and nanomolar IC(50) values towards a wide range of neoplastic and transformed cells. On occasions, greater toxicity towards neoplasms than normal cells has been demonstrated. A number of these compounds have in vivo anticancer properties and in general excellent tolerability in rodents is demonstrated. The way in which a number of physicochemical properties such as redox potentials, torsion angles, atomic charges and logP values govern cytotoxic potencies are presented. The importance of the shapes of different compounds as determined by molecular modeling in contributing to antineoplastic properties is outlined. Arguments are presented in favour of designing antineoplastics which have multiple sites of action in contrast to those bioactive molecules which have only one molecular target. A number of compounds which possess the dienone group have different modes of action some of which are chronicled in this review, such as inducing apoptosis, affecting respiration in mitochondria, inhibiting macromolecular biosynthesis and both inhibiting and stimulating certain enzymes. Other important properties of these compounds are discussed including their anti-angiogenic, MDR-revertant and antioxidant properties. It is hoped that this eulogy of the importance of the dienone group will encourage researchers to consider incorporating this structural unit into candidate cytotoxins in the future.

The effect of some 1-[4-(2-diethylaminoethoxy)phenylcarbonyl]-3,5-bis (benzylidene)-4-piperidone methiodides and related compounds on respiration and swelling of rat liver mitochondria.

The effect of a number of N-aroyl-3,5-bis(benzylidene)-4-piperidones 2 and related quaternary ammonium compounds 3 on the rates of respiration in rat liver mitochondria were determined. All of the compounds stimulated respiration and the greatest effect was displayed by the compounds in series 3 which caused swelling of mitochondria.

1-N-(Arylmaleamoyl)-3,5-bis(phenylmethylene)4-piperidones: a novel class of antimycobacterial agents.

Various acyl groups possessing markedly divergent topography were placed on the nitrogen atom of the antimycobacterial agent 3,5-bis(phenylmethylene)-4-piperidone (1). Some of the N-maleamoyl analogues of 1 displayed antitubercular properties thereby affording an insight into the structural requirements for interactions at a putative auxiliary binding site in the bacterium.

Anticonvulsants containing the N-(3-aryl-2-propenoyl) amido pharmacophore.

A series of 1-(3-aryl-2-propenoyl)-4-oxopiperidines (1) as well as some related semicarbazones (2) and thiosemicarbazones (3) were prepared in order to determine whether the relative locations of aryl rings and amidic groups would lead to novel anticonvulsant agents. Initially the compounds were administered intraperitoneally to mice and examined in the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and neurotoxicity (NT) screens. The biodata revealed that anticonvulsant properties were displayed by most of the compounds in series (1), in half of the semicarbazones (2) while protection was absent by members of series (3). Molecular modeling was utilized in order to compare the positions of a phenyl ring in relation to amidic groups in representative compounds in series (1-3) with previously reported anticonvulsant agents. Molecular simplification of 4-oxo-1-(3-phenyl-2-propenoyl)piperidine (la) led to 1-(3-phenyl-2-propenoyl)piperidine (7) and N,N-diethylcinnamamide (8) with retention of anticonvulsant properties. Both (la) and (8) afforded protection in the hippocampal kindling screen in rats. When administered orally to rats, (la) and (8) demonstrated activity in the MES screen and in the case of (8), a huge protection index was observed revealing it to be an important lead compound. The IC50 values of all of the compounds towards murine P388 cells were in excess of 50 microM while several compounds displayed cytotoxicity towards Mycobacterium tuberculosis.

Antimycobacterial arylidenecyclohexanones and related Mannich bases.

Several series of 2-arylidenecyclohexanones and related Mannich bases as well as various 2,6-bis(arylidene)cyclohexanones were evaluated against Mycobacterium tuberculosis H37Rv. Using a concentration of 12.5 microg/ml, nearly half of the unsaturated ketones inhibited the growth of the microorganism by 21-66% while all of the Mannich bases achieved 99% or greater inhibition. The relative hydrophobicities and widths of the molecules may have been contributing factors as to whether bioactivity was present or absent. Two of the Mannich bases demonstrated noteworthy potencies towards Mycobacterium avium. The conclusion was drawn that Mannich bases of 2-arylidenecyclohexanones represent a novel class of antimycobacterials.

Cytotoxic and topographical properties of 6-arylidene-2-dimethylaminomethylcyclohexanone hydrochlorides and related compounds.

A number of 2-arylidenecyclohexanones (1a-h) were converted into the corresponding Mannich bases (2a-h) and (3a,f). Evaluation against murine L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes revealed the marked cytotoxicity of the Mannich bases and also the fact that almost invariably these compounds were more potent than the precursor enones (1a-h). Further evaluation of most of the Mannich bases towards a panel of nearly 60 human tumour cell lines confirmed their utility as potent cytotoxins. In this assay, the compounds showed growth-inhibiting properties greater than the anticancer alkylator melphalan. QSAR studies revealed that in some cell lines compounds possessing small electron-attracting aryl substituents showed the greatest potencies. Molecular modeling and X-ray crystallography demonstrated that various interatomic distances and torsion angles correlated with cytotoxicity. A representative compound (2a) demonstrated weak inhibiting properties towards human N-myristoyltransferase and stimulated a tyrosine protein kinase. A single dose of 100 mg/kg of most of the compounds did not prove to be lethal in mice.

Cytotoxic mannich bases of 1-arylidene-2-tetralones.

Various 1-arylidene-2-tetralones 1 had been shown previously to possess moderate cytotoxic properties unaccompanied by murine toxicity. The objective of the present investigation was to undertake different molecular modifications of representative members of series 1 with a view to discerning those structural features leading to increased potencies. All compounds were evaluated using human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. The Mannich bases 2, 4, 5 and 7 possessed increased potencies compared to the corresponding unsaturated ketones 1 and in general were potent cytotoxics having IC50 values in the 0.2-10 microM range. QSAR using the cytotoxicity data for 2a-e suggested that potency was positively correlated with the size of the substituents in the arylidene aryl ring. Compounds 2a-f were evaluated using a panel of approximately 53 human tumour cell lines and, when all cell lines were considered, were more potent than the reference drug melphalan. In particular, marked antileukemic activity was displayed. Molecular modeling was utilized in order to evaluate whether the shapes of the different compounds contributed to the varying potencies observed. Representative compounds demonstrated minimal or no inhibiting properties towards human N-myristoyltransferase (NMT) and did not bind to calf thymus DNA. This study has revealed a number of unique lead molecules as candidate anti-neoplastic agents serving as prototypes for future development.

3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones: a novel group of cytotoxic agents.

A series of novel 3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones 3 have been synthesized which displayed potent cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. In contrast, the related N-arylmaleamic acids 4 possessed little or no cytotoxicity in these four screens. Molecular modeling revealed certain interplanar and bond angles and interatomic distances which were perceived to contribute to the observed bioactivity as well as providing suggestions for future structural modifications of the piperidones 3. Evaluation of representative compounds in series 3 and 4 on the activity of human N-myristoyltransferase revealed that, at the maximum concentration utilized, namely 250 microM, only weak inhibiting properties were displayed by some of the compounds in series 4. Various members of series 3 and 4 were well tolerated in mice.

Cytotoxic 4'-aminochalcones and related compounds.

A series of 4'-aminochalcones 1 and related maleamic acids 2 and Schiff bases 3 were designed and synthesized as candidate cytotoxic agents. The atomic charges on different atoms of representative compounds were calculated. Evaluation of the enones 1-3 against human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells revealed that approximately 40% of the IC50 values generated were less than 10 microM. In some cases cytotoxicity was correlated with the Hammett sigma values of the aryl substituents and less frequently with the aryl Hansch pi values. Evidence was obtained that in general these compounds displayed selective toxicity for certain malignant cells and were well tolerated in mice. This study has revealed various directions whereby the project may be amplified in the future with a view to finding compounds with increased cytotoxicity to tumour cells.