Complete Reversal Research Articles

Spectroscopic and structural implications of hosting Zn2+, Cd2+ and Hg2+ ions in the AgInS2 quantum dots

This work address the issue of spectral implications provided by doping AgInS 2 QDs with Zn 2+ and its higher homologues including Cd 2+ and Hg 2+ . The impact of alloying AgInS 2 QD with IIB group atoms is here discussed in terms of comprehensive spectroscopic measurements as well as theoretical predictions performed within the Density Functional Theory. It is shown that each of the admixtures used induces a completely different spectral response including complete reversal character for Cd 2+ and Hg 2+ ions. Observed differences were here associated with changes in the native defects structure and possible relaxation pathways due to doping. It is shown that Zn 2+ ions results in quite weak impact on the emission properties of the AgInS 2 QDs. Highest impact was found for Cd 2+ and Hg 2+ ions. Doping AgInS 2 QDs with Cd 2+ results in successive deactivation of the relaxation pathways which were typical for pristine AgInS 2 QDs leading to significant shortening of the photoluminescence lifetime and partial band symmetrisation. Doping with Hg 2+ ions was found to be of completely opposite character. It was found that mercury adatom has the lowest affinity to the AgInS 2 surface giving rise to formation of metallic Hg-Ag complexes on a surface which may be responsible for anomalous behaviour of Hg-doped AgInS 2 QDs. • Alloying AgInS 2 QDs with Cd and Hg is of different nature to that observed for Zn. • Spectral changes induced by Zn, Cd and Hg alloying are caused by native defects. • Doping with Zn, Cd and Hg ions may either partially passivate or induce defects formation. • Both Cd and Hg ions have much stronger impact on the defects structure than Zn ions. • Mercury dopants form metallic Hg-Ag complexes in AgInS 2 resulting in spectral redshift.

A highly regio- and stereoselective Pd-catalyzed electrocarboxylation of Baylis-Hillman acetates: An interesting switchable regioselectivity based on electrode material

We developed a novel regio- and stereoselective palladium catalyzed electrocarboxylation of Baylis-Hillman acetates. We found an interesting unprecedented electrode material-controlled switchable regioselectivity. When Platinum was taken as cathode, benzylic carboxylation products were found to be the predominant regioisomers (condition A). Under similar reaction conditions when Nickel was taken as cathode, a complete reversal in regioselectivity was observed providing cinnamyl carboxylation products as the predominant regio isomers with exclusively (E)-stereochemistry (condition B). We proposed plausible mechanisms to explain the switch in regioselectivity which were further supported by TEMPO experiments.

Enantioselectivity and mechanisms of chiral herbicide biodegradation in hydroponic systems

This study demonstrates the enantioselective removal dynamics and mechanisms of the chiral herbicide metolachlor in a hydroponic system of Phragmites australis. It presents the first work to elucidate plant-microbial driven enantioselective degradation processes of chiral chemicals. The results showed a degradation efficiency of up to 95.07 ± 2.81% in the hydroponic system driven by a notably high degradation rate constant of 0.086 d−1. P. australis was demonstrated to rapidly increase the contribution of biodegradation pathways in the hydroponic system to 82.21 ± 4.81% within 4 d with an enantiomeric fraction (EF) drop to 0.26 ± 0.02 to favour the enantioselective degradation of S-Metolachlor (kS-Metolachlor = 0.568 d−1 and kR-Metolachlor = 0.147 d−1). Comparatively, the biodegradation pathways in the control constituted less than 25%, with an EF value of circa 0.5. However, the enantioselective biodegradation pathways exhibited complete reversal after about 4 d to favour R-Metolachlor. Plants promoted the degradation of R-Metolachlor, evidenced by an increase in EF to 0.59 ± 0.03. Nonetheless, metolachlor showed an inhibitory effect on plants reflected by the reduction of plant growth rate, chlorophyll content, and electron transport rate to −7.85 ± 1.52%, 1.33 ± 0.43 mg g−1, 4.03 ± 1.33 μmol (m2 s)−1, respectively. However, rhizosphere microorganisms aided plants to catalyze excessive reactive oxygen species production by the antioxidant enzymes to protect plants from oxidative damage and restore their physiological activities. High-throughput analysis of microbial communities demonstrated the enrichment of Massilia (40.63%) and Pseudomonas (8.16%) in the initial stage to promote the rapid degradation of S-Metolachlor. By contrast, the proliferation of Brevundimonas (32.29%) and Pseudarthrobacter (11.03%) in the terminal stage was closely associated with the degradation of R-Metolachlor. Moreover, as symbiotic bacteria of plants, these bacteria aided plants protection from reactive oxygen damages and promoted the recovery of plant metabolic functions and photosynthesis. Overall, these results demonstrate biodegradation mediated by plant-microbe mechanisms as the main driver for the enantioselective degradation of metolachlor in hydroponic systems.

Potentiation of morphine antinociception and inhibition of diabetic neuropathic pain by the multi-chemokine receptor antagonist peptide RAP-103

AimsWe determined the ability of the multi-chemokine receptor (CCR2/CCR5/CCR8) antagonist RAP-103 to modulate pain behaviors in an acute model of surgical pain, with and without an added opioid (morphine), and by itself in a chronic model of Streptozotocin (STZ)-induced diabetic peripheral neuropathy (DPN). Materials and methodsPain behaviors were assessed by mechanical and thermal tests in rats. Cytokine and chemokine biomarkers in sciatic nerve and spinal cord were assessed by in situ qPCR. Key findingsIn the incisional pain assay, RAP-103 (0.01–1 mg/kg, i.p.) alone had no antiallodynic effect post-surgery. RAP-103 (0.5 mg/kg) when co-administered with morphine (0.5–5 mg/kg), reduced the ED50 of morphine from 3.19 mg/kg to 1.42 mg/kg. In a DPN model, rats exhibited persistent mechanical and cold allodynia. Oral administration of RAP-103 (0.5–0.02 mg/kg/day) resulted in a complete reversal of established hypersensitivity in DPN rats (P < .001), which gradually returned to pain hypersensitivity after the cessation of the treatment. The mRNA expression of cytokines, IL-1β, TNFα; chemokines CCL2, CCL3; and chemokine receptors CCR2 and CCR5 in DPN rat sciatic nerve, but not spinal cord, were significantly increased. RAP-103 resulted in significant reductions in sciatic nerve expression of IL-1β, TNFα and CCL3 in STZ-induced diabetic rats with trends toward lower levels for CCL2 and CCR5, while CCR2 was unchanged. SignificanceIn acute pain, co-administration of RAP-103 with morphine provided the same antinociceptive effect with a reduced dose of morphine, reducing opioid side-effects and risks. RAP-103 by itself is an effective non-opioid antinociceptive treatment for diabetic neuropathic pain.

Lectures on Dostoevsky by Joseph Frank

Reviewed by: Lectures on Dostoevsky by Joseph Frank Christina Karakepeli Lectures on Dostoevsky. By Joseph Frank. Princeton: Princeton University Press. 2019. xxv+248 pp. £25. ISBN 978–0–691–17896–7. In Lectures on Dostoevsky, Joseph Frank calls on the reader to make the effort 'of imagining ourselves back to the world in which [the novels] were written' (p. 75). 'Let us remember Dostoevsky's own historical position', he urges. '[T]o reach the heights by the road that Dostoevsky as author meant for us to follow', we must start 'from the ground up' (p. 138). This 'ground up' approach features throughout Frank's volume of insightful and meticulously structured essays on Dostoevskii. Through his patient and expertly researched reconstruction of Dostoevskii's biography—the result of decades-long study of the writer's life and work—Frank attempts to explain how the socio-cultural context of nineteenth-century Russia determined the evolution of Dostoevskii's beliefs and literary talents. These posthumously published lectures are based on a ten-week course that Frank gave at the Slavic Department of Stanford University while working on his magnum opus, his five-volume biography of Dostoevskii published over twenty-five years (1976–2002) by Princeton University Press. It was abridged in 2010 in a one-volume edition as Dostoevsky: A Writer in his Time. Frank distilled the knowledge, observations, and insights described in the five-volume biography (in infinitely more detail) into thirteen lectures. They begin with Dostoevskii's biography and historico-cultural background before delving deep into seven of the major novels in chronological order—Poor Folk, The Double, The House of the Dead, Notes from the Underground, Crime and Punishment, The Idiot, and The Brothers Karamazov—with the notable (if puzzling) exception of Demons. Frank narrates the ideological formation of Dostoevskii, the man and author, by pausing on the events that shaped his life—the early success of Poor Folk, involvement in the Petrashevskii Circle, mock execution, five years in a Siberian prison camp, and ideological struggles with the radical Nihilists. At every stage, as Frank shows, these events precipitated a consolidation (and not a complete reversal, as other critics often argue) of Dostoevskii's core beliefs: the precedence of faith over reason and the preservation—at all costs—of the individual's inner freedom. In these lectures, Frank describes how Dostoevskii's first novel Poor Folk continued and expanded on the literary tradition of Pushkin and Gogolʹ, and how Dostoevskii made his first attempts at what he himself called 'fantastic realism' in The Double. He also discusses the 'regeneration of [Dostoevskii's] convictions' (p. 45) after his imprisonment, attested by the semi-autobiographical The House of the Dead; the Underground Man's 'symbolic figure of revolt' (p. 73) in Notes from the Underground; the false promise of utilitarian humanitarianism in Crime and Punishment; the tragedy of Christ-like Prince Myshkin in The Idiot; and finally, the grand scale of The Brothers Karamazov. [End Page 518] The lectures are full of novel, authoritatively argued insights. Frank makes new connections and clears up previous misunderstandings (or what he calls 'historical errors') by attributing Dostoevskii's inspiration to the (historically) correct ideological source, a notable example being Dmitrii Pisarev's articles, cited as the inspiration for Raskolʹnikov's ideas. Frank re-evaluates hitherto less familiar works such as The Peasant Marei and Winter Notes on Summer Impressions, examining how they fit within the larger scheme of Dostoevskii's ideological progress. He draws attention to sources whose significance has not previously been appreciated, such as Dostoevskii's letter to his brother Mikhail after the mock execution; the journal entry after his first wife's death; and how the image of Christ he conjured there was finally embodied in The Idiot's Prince Myshkin. Frank pre-empts one possible criticism of this book: that a sole focus on the socio-historical context can sometimes prove reductive, precluding any abstract psychological or philosophical analysis of Dostoevskii's work. Frank is well aware that 'a great work of art always transcends the conditions of its creation and has meanings that go far beyond what its own period might have thought about it' (p. 138...

Surface‐Driven Evolution of the Anomalous Hall Effect in Magnetic Topological Insulator MnBi2Te4 Thin Films (Adv. Funct. Mater. 28/2022)

Magnetic Topological Insulators Targeted modification of properties is crucial to engineer novel phenomena such as the quantum anomalous Hall effect. In article number 2202234, Gyula Eres, Matthew Brahlek, and co-workers show that the anomalous Hall effect in the magnetic topological insulator MnBi2Te4 is highly tunable, to the point of complete sign reversal, by modification of the top-most layer via oxidation, which is linked to a subtle rebalancing of the global magnetic state.

Time To Re-Think and Rebuild: Need to Minimize the Pill and Re-Emphasize the Role of Risk Factors Modification in Life Style Disorders

An increase of lifestyle diseases (LSDs) has been driven by predominantly four important risk factors viz. unhealthy diet, hazardous alcohol use, tobacco use and physical inactivity. The present paper is envisioned to emphasize personal viewpoints and elucidations about vital role of behavioral risk factors in the management of lifestyle diseases particularly regarding Obesity, Type 2 Diabetes (T2DM) and Hypertension as well as an associated risk of pharmacological measures in treating such illnesses. Type 2 Diabetes is considered as irreversible and incurable chronic disease based on traditional means of management. Though, the current research promotes complete reversal of diabetes with the help of simple lifestyle measures. Health care professionals are encouraged to converse with their patients regarding health benefits of exercise, healthy diet and other lifestyle measures. Patient centered behaviour involving reducing tobacco use, controlling alcohol consumption, improving sleep patterns, balanced diet and mental wellbeing should be targeted by health care professional. Early diagnosis, prompt initiation of healthy lifestyle measures and delayed drug treatment could be an effective strategy not only to combat LSDs but also to develop positive attitudes towards life.

Two duplicated gsdf homeologs cooperatively regulate male differentiation by inhibiting cyp19a1a transcription in a hexaploid fish.

Although evolutionary fates and expression patterns of duplicated genes have been extensively investigated, how duplicated genes co-regulate a biological process in polyploids remains largely unknown. Here, we identified two gsdf (gonadal somatic cell-derived factor) homeologous genes (gsdf-A and gsdf-B) in hexaploid gibel carp (Carassius gibelio), wherein each homeolog contained three highly conserved alleles. Interestingly, gsdf-A and gsdf-B transcription were mainly activated by dmrt1-A (dsx- and mab-3-related transcription factor 1) and dmrt1-B, respectively. Loss of either gsdf-A or gsdf-B alone resulted in partial male-to-female sex reversal and loss of both caused complete sex reversal, which could be rescued by a nonsteroidal aromatase inhibitor. Compensatory expression of gsdf-A and gsdf-B was observed in gsdf-B and gsdf-A mutants, respectively. Subsequently, we determined that in tissue culture cells, Gsdf-A and Gsdf-B both interacted with Ncoa5 (nuclear receptor coactivator 5) and blocked Ncoa5 interaction with Rora (retinoic acid-related orphan receptor-alpha) to repress Rora/Ncoa5-induced activation of cyp19a1a (cytochrome P450, family 19, subfamily A, polypeptide 1a). These findings illustrate that Gsdf-A and Gsdf-B can regulate male differentiation by inhibiting cyp19a1a transcription in hexaploid gibel carp and also reveal that Gsdf-A and Gsdf-B can interact with Ncoa5 to suppress cyp19a1a transcription in vitro. This study provides a typical case of cooperative mechanism of duplicated genes in polyploids and also sheds light on the conserved evolution of sex differentiation.

Geochemical Characteristics and Origin of Shale Gases From Sichuan Basin, China

Natural gases from the Taiyang (shallow), Jiaoshiba (middle), and Weirong (deep) shale gas fields in the southern Sichuan Basin were analyzed for molecular and stable carbon isotopic compositions to investigate the geochemical characteristics and gas origins. All the gases belong to shale gas from the Upper Ordovician–Lower Silurian shale and are dominated by methane with gas wetness generally less than 0.83%. The δ13C1 values are −28.5‰, −30.3‰, and −35.2‰ in Taiyang, Jiaoshiba, and Weirong shale gas fields, respectively. The extremely high thermal maturity is the controlling factor for the enrichment of 13C in methane, with a minor contribution from the heavy carbon isotope of the organic matter in the Ordovician Wufeng Formation. Fischer–Tropsch-type synthesis of hydrocarbon gas from CO2 and H2 contributes to the increase of wet gas, which results in the offset from the δ13C1∼wetness linear trend in the Taiyang and Jiaoshiba gas fields. Methane, ethane, and propane in the Taiyang shale gas field have increasing δ13C values with increasing burial depth, which is mainly caused by diffusive migration. All gases are characterized by a complete carbon isotopic reversal trend (δ13C1 &amp;gt; δ13C2 &amp;gt; δ13C3), and it is mainly caused by the reversible free-radical reactions with the conversion from alkane to alkyl groups, with some contribution from the Fischer–Tropsch-type synthesis. The results of this study will improve our understanding of the geochemical characteristics of shale gases from different burial depths and have important implications for future shale gas exploration in the deep and shallow layers.

Impact of the COVID-19 crisis on the mortality profiles of the foreign-born in France during the first pandemic wave

BackgroundImmigrants in Western countries have been particularly affected by the COVID-19 crisis. ObjectiveWe analysed excess mortality rates among the foreign-born population and changes in their distinctive mortality profiles (“migrant mortality advantage”) during the first pandemic wave in France. Data and methodsDeaths from all causes in metropolitan France from March 18 to May 19, 2020 were used, with information on sex, age, region of residence and country of birth. Similar data from 2016 through 2019 were used for comparisons. ResultsDuring the pre-pandemic period (2016–2019), immigrant populations (except those from Central and Eastern Europe) had lower standardized mortality rates than the native-born population, with a particularly large advantage for immigrants from sub-Saharan Africa. In the regions most affected by COVID-19 (Grand-Est and Île-de-France), the differences in excess mortality by country of birth were large, especially in the working-age groups (40–69 years), with rates 8 to 9 times higher for immigrants from sub-Saharan Africa, and about 3 to 4 times higher for immigrants from North Africa, from the Americas and from Asia and Oceania relative to the native-born population. The relative overall mortality risk for men born in sub-Saharan Africa compared to native-born men, which was 0.8 before the pandemic, shifted to 1.8 during the first wave (0.9 to 1.5 for women). It also shifted from 0.8 to 1.1 for men from North Africa (0.9 to 1.1 for women), 0.7 to 1.0 for men from the Americas (0.9 to 1.3 for women), and 0.7 to 1.2 for men from Asia and Oceania (0.9 to 1.3 for women). ConclusionOur findings shed light on the disproportionate impact of the first wave of the pandemic on the mortality of populations born outside Europe, with a specific burden of excess mortality within the working-age range, and a complete reversal of their mortality advantage.

Effect of quasi hydrostatic and non hydrostatic pressure on long S–S bonded sodium dithionite (Na2S2O4): A Raman Spectroscopic study

Sodium dithionite, Na2S2O4, most commonly used reducing agent, is known to exist in equilibrium as [SO2−.] radical state in aqueous solution due to the easy cleavage of its very long S–S bond (2.389 ​Å). Overall, the structure of Na2S2O4 is akin to linkage system, where long S–S bond as a main bar is flanked by two short S–O bonds in eclipsed position. This prompted us to undertake solid state behaviour of Na2S2O4 under quasi-hydrostatic (up to 34.5 ​GPa) and non-hydrostatic (30.2 ​GPa) pressure environments using diamond anvil cell and Raman spectroscopy. Although increase in pressure, under both pressure environments, clearly showed blue shifting of the main vibrational modes, with some changes in dω/dP, relationship is observed between stretching of S–S bonds and stretching of S–O bonds. Interestingly, the pressure values of ∼0.3 ​GPa, ∼3.2 ​GPa, ∼7.8 ​GPa, and ∼18.7 ​GPa at which changes were observed in Raman spectra of Na2S2O4, have similarity in pressure values with those observed in high pressure studies of SO2 in literature. More importantly, development of a new S–S- bond around 261 ​cm−1 ​at high frequency side was observed under quasi-hydrostatic as well as non-hydrostatic pressure environment above 7.8 ​GPa, during compression which showed complete reversibility on decompression. These results can help as a simple model for understanding reactivity of disulphide bridged systems, especially proteins, under external stress.

Evaluation of the Efficiency of Functional Reversal of Fatty Acid Β-Oxidation in Escherichia coli upon the Action of Various Native Acyl-CoA Dehydrogenases

Using Escherichia coli strain MG1655 lacIQ, ∆ackA-pta, ∆poxB, ∆ldhA, ∆adhE, ∆fadE, PL‑SDφ10-atoB, Ptrc-ideal-4-SDφ10-fadB, PL-SDφ10-tesB, ∆yciA as a core strain, the efficiency of the reversal of fatty acid β-oxidation upon the action of native cellular enzymes capable of serving as acyl-CoA dehydrogenases was examined. Increased expression of fadE, fabI, and ydiO/ydiQRST genes encoding the corresponding enzymes was ensured in derivatives of the core strain by substituting their native regulatory regions with artificial regulatory element Ptrc-ideal-4-SDφ10. A three-turn reversal of the cycle in the engineered recombinants was demonstrated that was accompanied by considerable secretion of butyric, caproic, and caprylic acids. The highest level of six- and eight-carbon carboxylates production was achieved upon the overexpression of the fabI gene, while the lowest levels of secretion of the corresponding compounds were demonstrated by the strain with the enhanced expression of the ydiO and ydiQRST genes. The recombinant with the individually enhanced expression of ydiO did not produce detectable amounts of the derivatives of the complete and successful β-oxidation reversal.

1327-P: Loss of Exocrine Pancreas Improves Glucose Tolerance and Insulin Secretion in Diet-Induced Hyperglycemia

There are two intra-pancreatic axes of communication between the endocrine and exocrine pancreas (insular-acinar &amp; acinar-insular axes) yet the study of the endocrine and exocrine pancreas have generally been conducted separately. We previously showed that loss of acinar cells improved glucose homeostasis in wild type mice. Here, we examined the effect of loss of acinar cells on diet-induced hyperglycemia.We used a genetic mouse model (ElaCreERT2; R26DTR) , wherein diphtheria toxin (DT) ablates acinar cells, allowing for the study of β-cell function in the absence of acinar cells. We included 3 groups [ElaCreERT2; R26DTR + high fat diet (HFD) ], [R26DTR + HFD], and [R26DTR + regular diet (RD) ]. These groups were on their respective diets for 12 weeks, then underwent glucose tolerance testing (GTT) and glucose stimulated insulin secretion (GSIS) after DT injection. Four days post-DT, the ElaCreERT2; R26DTR+HFD mice had a significantly improved glucose tolerance compared to R26DTR + HFD (AUC p=0.0003) . Importantly, the ElaCreERT2; R26DTR + HFD were not different from R26DTR+RD, indicating complete reversal of the hyperglycemia. GSIS done during GTT showed significantly lower insulin secretion in ElaCreERT2; R26DTR + HFD compared to R26DTR + HFD (AUC p=0.0388) , but similar to R26DTR+ RD, again indicating normalization. Islets were isolated from the 3 groups for in vitro GSIS, which showed no difference in the insulin secretion between ElaCreERT2; R26DTR + HFD and R26DTR + RD, but both had increased insulin secretion compared to R26DTR + HFD. Four weeks post-DT, when full regeneration of acinar cells from duct cells takes place, repeat GTT in the same animals showed that HFD groups had worse glucose tolerance compared to the RD group, suggesting that it was specifically the loss of the acinar cells that improved glucose tolerance. We conclude that the acute ablation of exocrine pancreas improves glucose tolerance and reverses HFD-induced hyperglycemia by enhancing insulin secretion. Disclosure S.Abi raad: None. M.Saleh: None. G.Gittes: None.

Photo De‐Mixing in Dion‐Jacobson 2D Mixed Halide Perovskites

Abstract2D halide perovskites feature a versatile structure, which not only enables the fine‐tuning of their optoelectronic properties but also makes them appealing as model systems to investigate the fundamental properties of hybrid perovskites. In this study, the authors analyze the changes in the optical absorption of 2D Dion‐Jacobson mixed halide perovskite thin films (encapsulated) based on (PDMA)Pb(I0.5Br0.5)4 (PDMA: 1,4‐phenylenedimethanammonium spacer) exposed to a constant illumination. It is demonstrated that these 2D mixed‐halide perovskites undergo photo‐induced phase segregation, where the pristine mixed‐phase de‐mixes into iodide‐rich and bromide‐rich phases (photo de‐mixing). The de‐mixed state is largely maintained in the dark at room temperature for several months, while at higher temperatures it shows complete reversibility to the mixed‐phase in terms of optical and structural properties (dark re‐mixing). The authors further investigate temperature‐dependent absorption measurements under light to extract the photo de‐mixed compositions and to map the photo‐miscibility‐gap. This work thereby reveals that reversible photo de‐mixing occurs in Dion‐Jacobson 2D hybrid perovskites and provides strategies to address the role of light in the thermodynamic properties of these materials.

Behavioral and inflammatory sex differences revealed by celecoxib nanotherapeutic treatment of peripheral neuroinflammation

Neuropathic pain affects millions of people worldwide, yet the molecular mechanisms of how it develops and persists are poorly understood. Given that males have historically been utilized as the primary sex in preclinical studies, less is known about the female neuroinflammatory response to injury, formation of pain, or response to pain-relieving therapies. Macrophages contribute to the development of neuroinflammatory pain via the activation of their cyclooxygenase-2 (COX-2) enzyme, which leads to the production of prostaglandin E2 (PGE2). PGE2 activates nociception and influences additional leukocyte infiltration. Attenuation of COX-2 activity decreases inflammatory pain, most commonly achieved by nonsteroidal anti-inflammatory drugs (NSAIDs), yet NSAIDs are considered ineffective for neuropathic pain due to off target toxicity. Using chronic constriction injury of the rat sciatic nerve, we show that males and females exhibit quantitatively the same degree of mechanical allodynia post injury. Furthermore, a low-dose nanotherapeutic containing the NSAID celecoxib is phagocytosed by circulating monocytes that then naturally accumulate at sites of injury as macrophages. Using this nanotherapeutic, we show that treated males exhibit complete reversal of hypersensitivity, while the same dose of nanotherapeutic in females provides an attenuated relief. The difference in behavioral response to the nanotherapy is reflected in the reduction of infiltrating macrophages at the site of injury. The observations contained in this study reinforce the notion that female neuroinflammation is different than males.

Implications for health system reform, workforce recovery and rebuilding in the context of the Great Recession and COVID-19: a case study of workforce trends in Ireland 2008–2021

BackgroundWorkforce is a fundamental health systems building block, with unprecedented measures taken to meet extra demand and facilitate surge capacity during the COVID-19 pandemic, following a prolonged period of austerity. This case study examines trends in Ireland’s publicly funded health service workforce, from the global financial crisis, through the Recovery period and into the COVID-19 pandemic, to understand resource allocation across community and acute settings. Specifically, this paper aims to uncover whether skill-mix and staff capacity are aligned with policy intent and the broader reform agenda to achieve universal access to integrated healthcare, in part, by shifting free care into primary and community settings.MethodsSecondary analysis of anonymised aggregated national human resources data was conducted over a period of almost 14 years, from December 31st 2008 to August 31st 2021. Comparative analysis was conducted, by professional cadre, across three keys periods: ‘Recession period’ December 31st 2008–December 31st 2014; ‘Recovery period’ December 31st 2014–December 31st 2019; and the ‘COVID-19 period’ December 31st 2019–August 31st 2021.ResultsDuring the Recession period there was an overall decrease of 8.1% (n = 9333) between December 31st 2008 and December 31st 2014, while the Recovery period saw the overall staff levels rebound and increase by 15.2% (n = 16,789) between December 31st 2014 and December 31st 2019. These figures continued to grow, at an accelerated rate during the most recent COVID-19 period, increasing by a further 8.9% (n = 10,716) in under 2 years. However, a notable shift occurred in 2013, when the number of staff in acute services surpassed those employed in community services (n = 50,038 and 49,857, respectively). This gap accelerated during the Recovery and COVID-19 phase. By August 2021, there were 13,645 more whole-time equivalents in acute settings compared to community, a complete reverse of the 2008 situation. This was consistent across all cadres. Workforce absence trends indicate short-term spikes resulting from shocks while COVID-19 redeployment disproportionately impacted negatively on primary care and community services.ConclusionsThis paper clearly demonstrates the prioritisation of staff recruitment within acute services—increasing needed capacity, without the same commitment to support government policy to shift care into primary and community settings. Concerted action including the permanent redistribution of personnel is required to ensure progressive and sustainable responses are learned from recent shocks.

Capacitance-based stress self-sensing in asphalt without electrically conductive constituents, with relevance to smart pavements

The capacitance-based stress self-sensing in asphalt without device or functional constituent incorporation is reported for the first time, with relevance to smart pavements. Stress sensing enables weighing. Without the incorporation, the technology is applicable to existing and new pavements, and gives low cost, high durability, large sensing volume and maintained mechanical properties. Linearity of the capacitance with the normal compressive stress occurs for stress ranging from 2 Pa to 60 Pa. The ability to sense such low stress enables the sensing of even children. Nonlinearity at > 60 Pa involves the slope of the capacitance-stress curve decreasing. Monotonic and reversible capacitance increase with stress occurs for stress ≤ 600 Pa, with complete reversibility up to stress ≥ 2100 Pa. The electrodes are aluminum foil bonded to the asphalt with a thin bitumen interlayer. With coplanar electrodes (the stress not applied to the electrodes), the in-plane capacitance increases upon compression, presumably due to the compaction of the part of the asphalt near the plane of the coplanar electrodes. With sandwiching electrodes (the stress applied to the electrodes), the through-thickness capacitance increases reversibly upon compression, due to the decrease in the thickness of the bitumen interlayer. The coplanar electrodes enable self-sensing, and, compared to the sandwiching electrodes, they give much greater sensitivity and are more amenable to practical implementation. The sensing is based on the fractional change in capacitance, so the thickness of the asphalt or bitumen interlayer does not matter. The capacitance-based stress sensing is superior for asphalt than cement-based materials of prior work, due to the greater stiffness of the latter.

Reversal of Right Ventricular Hypertrophy and Dysfunction by Prostacyclin in a Rat Model of Severe Pulmonary Arterial Hypertension.

Prostacyclin analogs are among the most effective and widely used therapies for pulmonary arterial hypertension (PAH). However, it is unknown whether they also confer protection through right ventricle (RV) myocardio-specific mechanisms. Moreover, the use of prostacyclin analogs in severe models of PAH has not been adequately tested. To further identify underlying responses to prostacyclin, a prostacyclin analogue, treprostinil, was used in a preclinical rat Sugen-chronic hypoxia (SuCH) model of severe PAH that closely resembles the human disease. Male Sprague–Dawley rats were implanted with osmotic pumps containing vehicle or treprostinil, injected concurrently with a bolus of Sugen (SU5416) and exposed to 3-week hypoxia followed by 3-week normoxia. RV function was assessed using pressure–volume loops and hypertrophy by weight assessed. To identify altered mechanisms within the RV, tissue samples were used to perform a custom RNA array analysis, histological staining, and protein and transcript level confirmatory analyses. Treprostinil significantly reduced SuCH-associated RV hypertrophy and decreased the rise in RV systolic pressure, mean pulmonary arterial (mPAP), and right atrial (RAP) pressure. Prostacyclin treatment was associated with improvements in RV stroke work, maximum rate of ventricular pressure change (max dP/dt) and the contractile index, and almost a complete reversal of SuCH-associated increase in RV end-systolic elastance, suggesting the involvement of load-independent improvements in intrinsic RV systolic contractility by prostacyclin treatment. An analysis of the RV tissues showed no changes in cardiac mitochondrial respiration and ATP generation. However, custom RNA array analysis revealed amelioration of SuCH-associated increases in newly identified TBX20 as well as the fibrotic markers collagen1α1 and collagen 3α1 upon treprostinil treatment. Taken together, our data support decreased afterload and load-independent improvements in RV function following prostacyclin administration in severe PAH, and these changes appear to associate with improvements in RV fibrotic responses.

Angle selective piezoelectric strain-controlled magnetization switching in artificial spin ice based multiferroic system

The prospect of electrically controlled writing of ferromagnetic bits is highly desirable for developing scalable and energy-efficient spintronics devices. In this direction, various efforts have been made to achieve electrically controlled magnetization switching utilizing an artificial multiferroic system. To date, the magnetization switching has been realized in a diverse nanopatterned magnetic system. However, the demonstration of electric field-induced strain-controlled magnetization switching in artificial spin ice (ASI) coupled with a piezoelectric material is still unexplored. In the present work, we perform micromagnetic simulations to investigate the electric field-induced strain-mediated magnetization switching in an ASI based multiferroic system. Here, the piezoelectric strain-controlled magnetization switching has been studied by applying the electric-field pulse at different angles with respect to the axes of the system. Remarkably, magnetization switches by 180° only if the external electric-field pulse is applied at some specific angles, close to the anisotropy axis of the system (≈30°–60°). Our detailed analysis of the demagnetization energy variation reveals that the energy barrier becomes antisymmetric in such cases, facilitating complete magnetization reversal. Moreover, we have also proposed a possible magnetization reversal mechanism with two sequential electric-field pulses of a relatively smaller magnitude. We believe that the present work could pave the way for a future ASI-based multiferroic system for scalable magnetic field-free low power spintronics devices.

Suppression of glutathione system and upregulation of caspase 3-dependent apoptosis mediate rohypnol-induced gastric injury

ABSTRACT Objectives: This study investigated the impact of rohypnol on gastric tissue integrity. Methods: Forty male Wistar rats were randomized into control, low dose rohypnol-treated, high dose rohypnol-treated, low dose rohypnol-treated recovery and high dose rohypnol-treated recovery groups. Results: Rohypnol caused significant rise in gastric malondialdehyde (MDA), oxidized glutathione (GSSG), nitric oxide (NO), tumour necrotic factor-α (TNF-α), and interleukin-6 (IL-6) levels. Also, rohypnol caused reductions in gastric reduced glutathione (GSH) (as well as GSH/GSSG), and activities of superoxide dismutase (SOD), catalase, glutathione-S-transferase (GST), glutathione peroxidase (GPx), cyclo-oxygenase (COX-2). Furthermore, rohypnol upregulated caspase 3 activity and induced gastric DNA damage, evident by a rise in 8-hydroxydeoxyguanosine (8-OHdG) and DNA fragmentation index (DFI) in gastric tissue. These alterations were coupled with reduced gastric weight and distorted gastric cytoarchitecture. Cessation of rohypnol caused a significant but not complete reversal of rohypnol-induced gastric damage. Conclusion: This study revealed that rohypnol induced gastric injury by suppressing glutathione content and COX-2 activity, and upregulating caspase 3-dependent apoptosis, which was partly reversed by rohypnol withdrawal.