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JPMA. the Journal of the Pakistan... Jun 2024In this communication, we discuss the concept of psychological first aid, as relevant to diabetes management. Psychological first aid, in the diabetes care context, is...
In this communication, we discuss the concept of psychological first aid, as relevant to diabetes management. Psychological first aid, in the diabetes care context, is defined as "the empathic support, counselling and education to improve coping skills, and optimize selfcare of persons living with diabetes, so that psychological well-being can be optimized." Various models can help provide structured psychological first aid. We feel that each and every health care provider should be able to provide effective first aid, including psychological first aid.
Topics: Humans; Adaptation, Psychological; Counseling; Diabetes Mellitus; Patient Education as Topic; Self Care; Social Support; Empathy; First Aid
PubMed: 38949000
DOI: 10.47391/JPMA.24-45 -
JPMA. the Journal of the Pakistan... Jun 2024To assess the effect of haemodialysis practice guidelines on dialysis indicators and haemodynamic complications, the comparative study was conducted at the dialysis unit...
To assess the effect of haemodialysis practice guidelines on dialysis indicators and haemodynamic complications, the comparative study was conducted at the dialysis unit of Sheikh Zayed Hospital, Lahore, Pakistan, and comprised patients undergoing haemodialysis who were divided into intervention group A in which updated haemodialysis practice guidelines were used, and control group B in which routine base dialysis was given. Data was collected using a self-structured tool. Data was analysed using McNemar test and Mann-Whitney U-test with p<0.05. Compared to baseline, there was a significant improvement in post-intervention ratio of effective removal of clearance (K) resulting from the treatment characterised by time (t) in the patient with a specific volume of distribution (V), or Kt/V, median & IQR 0.83(0.355) vs 1.21(0.11) and percentage of urea reduction ratio with median & IQR 49(12) vs. 66.5(18.65) (p<0.05). Intradialytic hypotension was found in 17(56.6%) subjects in group B and in 4(13.4%) in group A (p=0.002). Intradialytic hypertension was found in 8(25.6%) patients in group B and 1(3.4%) in group A (p=0.039). It is recommended that dialysis be performed in accordance with the most recent clinical guidelines in order to improve practices and to increase haemodialysis effectiveness.
Topics: Humans; Renal Dialysis; Female; Male; Practice Guidelines as Topic; Middle Aged; Hypotension; Pakistan; Adult; Kidney Failure, Chronic; Hemodynamics; Hypertension; Aged; Urea
PubMed: 38948988
DOI: 10.47391/JPMA.8532 -
JPMA. the Journal of the Pakistan... Jun 2024To assess the knowledge of caregivers in a tertiary care setting about child abuse, their perception of potential barriers in the way of seeking medical advice for the...
Barriers to medical consultation and strategies for enhancing the prevention and reporting of child abuse: A cross-sectional survey of caregivers of paediatric patients at a tertiary care center in Karachi, Pakistan.
OBJECTIVE
To assess the knowledge of caregivers in a tertiary care setting about child abuse, their perception of potential barriers in the way of seeking medical advice for the victims, and to identify proposed solutions to ensure prevention and reporting of child abuse.
METHODS
The cross-sectional study was conducted from June to December 2022 at the paediatric ward of the Aga Khan University Hospital, Karachi, and comprised caregivers who were attendants of inpatients. Data was collected using a predesigned anonymous questionnaire consisting of demographic information and 27 items that were scored on a 6-point Likert scale. Data was analysed using SPSS 20.
RESULTS
Of the 144 caregivers, 96(66.6%) were females and 48(33.3%) were males. Overall, 86(59.7%) were aged <35 years, 132(91.7%) were married, and 120(83.3%) were the admitted child's parent. The majority of caregivers 110(76.4%) perceived themselves to possess a high level of knowledge about child abuse. Barriers identified included a lack of trust in police and medicolegal departments 136(94.4%), fear of repercussion from the suspect 120(83.3%) and lack of confidentiality of the victims' identity 116(80.6%). The proposed solutions included spreading awareness among teachers 136(94.4%) and caregivers 131(91.0%) about timely reporting and consultation, and developing proper mechanisms to follow-up on victims 133(92.4%). There were significant associations between some demographic characteristics of the respondents and their self-perceived knowledge and perceptions (p<0.05).
CONCLUSION
There was found a need to enhance public trust, ensure confidentiality, and fostering awareness through targeted strategies for a safer and more facilitative environment for children.
Topics: Humans; Pakistan; Female; Male; Cross-Sectional Studies; Adult; Child Abuse; Tertiary Care Centers; Health Knowledge, Attitudes, Practice; Child; Caregivers; Referral and Consultation; Surveys and Questionnaires; Trust; Mandatory Reporting
PubMed: 38948982
DOI: 10.47391/JPMA.10320 -
Advanced Healthcare Materials Jun 2024Osteochondral regeneration remains formidable challenges despite significant advances in microsurgery. Herein, an acellular trilayer cryogel (TC) with injectability,...
Osteochondral regeneration remains formidable challenges despite significant advances in microsurgery. Herein, an acellular trilayer cryogel (TC) with injectability, tunable pore sizes (80-200 µm), and appropriate compressive modulus (10.8 kPa) is manufactured from self-healable hydrogel under different gelling times through Schiff reaction between chitosan and difunctionalized polyurethane (DFPU). Bioactive molecules (Y27632 and dexamethasone) are respectively loaded in the top and bottom layers to form the Y27632/dexamethasone-loaded trilayer cryogel (Y/DEX-TC). Mesenchymal stem cells (MSCs) seeded in Y/DEX-TC proliferated ≈350% in vitro and underwent chondrogenesis or osteogenesis in response to the respective release of Y or DEX in 14 days. Acupuncture is administered to animals in an attempt to modulate the innate regulatory system and mobilize endogenous MSCs for osteochondral defect regeneration. In vivo rabbit experiments using Y/DEX-TC combined with acupuncture successfully regulate SDF-1 and TGF-β1 levels, which possibly cause MSC migration toward Y/DEX-TC. The synergistic effect of cryogel and acupuncture on immunomodulation is verified with a ≈7.3-fold enhancement of the M2-/M1-macrophage population ratio by treatment of Y/DEX-TC combining acupuncture, significantly greater than ≈1.5-fold increase by acupuncture or ≈2.2-fold increase by Y/DEX-TC alone. This novel strategy using acellular drug-loaded cryogel and accessible acupuncture shows promise in treating osteochondral defects of joint damage.
PubMed: 38948966
DOI: 10.1002/adhm.202400462 -
Advanced Materials (Deerfield Beach,... Jun 2024Interconnecting macromolecules via multiple hydrogen bonds (H-bonds) can simultaneously strengthen and toughen polymers, but material synthesis becomes extremely...
Interconnecting macromolecules via multiple hydrogen bonds (H-bonds) can simultaneously strengthen and toughen polymers, but material synthesis becomes extremely difficult with increasing number of H-bonding donors and acceptors; therefore, most reports are limited to triple and quadruple H-bonds. Herein, this bottleneck is overcome by adopting a quartet-wise approach of constructing H-bonds instead of the traditional pairwise method. Thus, large multiple hydrogen bonds can be easily established, and the supramolecular interactions are further reinforced. Especially, when such multiple H-bond motifs are embedded in polymers, four macromolecular chains-rather than two as usual-are tied, distributing the applied stress over a larger volume and more significantly improving the overall mechanical properties. Proof-of-concept studies indicate that the proposed intermolecular multiple H-bonds (up to duodecuple) are readily introduced in polyurethane. A record-high tensile strength (105.2 MPa) is achieved alongside outstanding toughness (352.1 MJ m), fracture energy (480.7 kJ m), and fatigue threshold (2978.4 J m). Meantime, the polyurethane has acquired excellent self-healability and recyclability. This strategy is also applicable to nonpolar polymers, such as polydimethylsiloxane, whose strength (15.3 MPa) and toughness (50.3 MJ m) are among the highest reported to date for silicones. This new technique has good expandability and can be used to develop even more and stronger polymers.
PubMed: 38948960
DOI: 10.1002/adma.202406574 -
BioRxiv : the Preprint Server For... Jun 2024Drugs of abuse activate defined neuronal ensembles in brain reward structures such as the nucleus accumbens (NAc), which are thought to promote the enduring synaptic,...
Drugs of abuse activate defined neuronal ensembles in brain reward structures such as the nucleus accumbens (NAc), which are thought to promote the enduring synaptic, circuit, and behavioral consequences of drug exposure. While the molecular and cellular effects arising from experience with drugs like cocaine are increasingly well understood, the mechanisms that sculpt NAc ensemble participation are largely unknown. Here, we leveraged unbiased single-nucleus transcriptional profiling to identify expression of the secreted glycoprotein Reelin (encoded by the gene) as a marker of cocaine-activated neuronal ensembles within the rat NAc. Multiplexed in situ detection confirmed selective expression of the immediate early gene in neurons after cocaine experience, and also revealed enrichment of mRNA in + medium spiny neurons (MSNs) in both the rat and human brain. Using a novel CRISPR interference strategy enabling selective knockdown in the adult NAc, we observed altered expression of genes linked to calcium signaling, emergence of a transcriptional trajectory consistent with loss of cocaine sensitivity, and a striking decrease in MSN intrinsic excitability. At the behavioral level, loss of prevented cocaine locomotor sensitization, abolished cocaine place preference memory, and decreased cocaine self-administration behavior. Together, these results identify Reelin as a critical mechanistic link between ensemble participation and cocaine-induced behavioral adaptations.
PubMed: 38948801
DOI: 10.1101/2024.06.17.599348 -
BioRxiv : the Preprint Server For... Jun 2024Despite improved life expectancy of people with HIV (PWH), HIV-associated neurocognitive impairment (NCI) persists, alongside deficits in sensorimotor gating and...
RATIONALE
Despite improved life expectancy of people with HIV (PWH), HIV-associated neurocognitive impairment (NCI) persists, alongside deficits in sensorimotor gating and neuroinflammation. PWH exhibit high smoking rates, possibly due to neuroprotective, anti-inflammatory, and cognitive-enhancing effects of nicotine, suggesting potential self-medication.
OBJECTIVES
Here, we tested the effects of acute nicotine vapor exposure on translatable measures of sensorimotor gating and exploratory behavior in the HIV-1 transgenic (HIV-1Tg) rat model of HIV.
METHODS
Male and female HIV-1Tg and F344 control rats (n=57) were exposed to acute nicotine or vehicle vapor. Sensorimotor gating was assessed using prepulse inhibition (PPI) of the acoustic startle response, and exploratory behavior was evaluated using the behavioral pattern monitor (BPM).
RESULTS
Vehicle-treated HIV-1Tg rats exhibited PPI deficits at low prepulse intensities compared to F344 controls, as seen previously. No PPI deficits were observed in nicotine-treated HIV-1Tg rats, however. HIV-1Tg rats were hypoactive in the BPM relative to controls, whilst nicotine vapor increased activity and exploratory behavior across genotypes. Cotinine analyses confirmed comparable levels of the primary metabolite of nicotine across genotypes.
CONCLUSIONS
Previous findings of PPI deficits in HIV-1Tg rats were replicated and, importantly, attenuated by acute nicotine vapor. Evidence for similar cotinine levels suggest a nicotine-specific effect in HIV-1Tg rats. HIV-1Tg rats had reduced exploratory behavior compared to controls, attenuated by acute nicotine vapor. Therefore, acute nicotine may be beneficial for remediating sensorimotor and locomotor activity deficits in PWH. Future studies should determine the long-term effects of nicotine vapor on similar HIV/NCI-relevant behaviors.
PubMed: 38948796
DOI: 10.1101/2024.06.18.599641 -
BioRxiv : the Preprint Server For... Jun 2024Oxidative stress is implicated in the pathogenesis and progression of abdominal aortic aneurysm (AAA). Antioxidant delivery as a therapeutic for AAA is of substantial...
BACKGROUND
Oxidative stress is implicated in the pathogenesis and progression of abdominal aortic aneurysm (AAA). Antioxidant delivery as a therapeutic for AAA is of substantial interest although clinical translation of antioxidant therapy has met with significant challenges due to limitations in achieving sufficient antioxidant levels at the site of AAA. We posit that nanoparticle-based approaches hold promise to overcome challenges associated with systemic administration of antioxidants.
METHODS
We employed a peptide-based nanoplatform to overexpress a key modulator of oxidative stress, superoxide dismutase 2 (SOD2). The efficacy of systemic delivery of SOD2 mRNA as a nanotherapeutic agent was studied in two different murine AAA models. Unbiased mass spectrometry-enabled proteomics and high-dimensional bioinformatics were used to examine pathways modulated by SOD2 overexpression.
RESULTS
The murine SOD2 mRNA sequence was mixed with p5RHH, an amphipathic peptide capable of delivering nucleic acids to form self-assembled nanoparticles of ∼55 nm in diameter. We further demonstrated that the nanoparticle was stable and functional up to four weeks following self-assembly when coated with hyaluronic acid. Delivery of SOD2 mRNA mitigated the expansion of small AAA and largely prevented rupture. Mitigation of AAA was accompanied by enhanced SOD2 protein expression in aortic wall tissue. Concomitant suppression of nitric oxide, inducible nitric oxide synthase expression, and cell death was observed. Proteomic profiling of AAA tissues suggests that SOD2 overexpression augments levels of microRNAs that regulate vascular inflammation and cell apoptosis, inhibits platelet activation/aggregation, and downregulates mitogen-activated protein kinase signaling. Gene set enrichment analysis shows that SOD2 mRNA delivery is associated with activation of oxidative phosphorylation, lipid metabolism, respiratory electron transportation, and tricarboxylic acid cycle pathways.
CONCLUSIONS
These results confirm that SOD2 is key modulator of oxidative stress in AAA. This nanotherapeutic mRNA delivery approach may find translational application in the medical management of small AAA and the prevention of AAA rupture.
PubMed: 38948794
DOI: 10.1101/2024.06.17.599454 -
BioRxiv : the Preprint Server For... Jun 2024Vertebrate radial glia progenitors (RGPs), the principal neural stem cells, balance self-renewal and differentiation through asymmetric cell division (ACD), during which...
Vertebrate radial glia progenitors (RGPs), the principal neural stem cells, balance self-renewal and differentiation through asymmetric cell division (ACD), during which unequal inheritance of centrosomes is observed. Mechanistically, how centrosome asymmetry leads to distinct daughter cell fate remains largely unknown. Here we find that the centrosome protein Pericentriolar Material 1 (Pcm1), asymmetrically distributed at the centrosomes, regulates polarized endosome dynamics and RGP fate. time-lapse imaging and nanoscale-resolution expansion microscopy of zebrafish embryonic RGPs detect Pcm1 on Notch ligand-containing endosomes, in a complex with the polarity regulator Par-3 and dynein motor. Loss of disrupts endosome dynamics, with clonal analysis uncovering increased neuronal production at the expense of progenitors. Pcm1 facilitates an exchange of Rab5b (early) for Rab11a (recycling) endosome markers and promotes the formation of Par-3 and dynein macromolecular complexes on recycling endosomes. Finally, in human-induced pluripotent stem cell-derived brain organoids, PCM1 shows asymmetry and co-localization with PARD3 and RAB11A in mitotic neural progenitors. Our data reveal a new mechanism by which centrosome asymmetry is conveyed by Pcm1 to polarize endosome dynamics and Notch signaling in regulating ACD and progenitor fate.
PubMed: 38948739
DOI: 10.1101/2024.06.17.599416 -
BioRxiv : the Preprint Server For... Jun 2024Anaphase is tightly controlled in space and time to ensure proper separation of chromosomes. The mitotic spindle, the self-organized microtubule structure driving...
Anaphase is tightly controlled in space and time to ensure proper separation of chromosomes. The mitotic spindle, the self-organized microtubule structure driving chromosome segregation, scales in size with the available cytoplasm. Yet, the relationship between spindle size and chromosome movement remains poorly understood. Here, we address how the movement of chromosomes changes during the cleavage divisions of the blastoderm. We show that the speed of chromosome separation gradually decreases during the 4 nuclear divisions of the blastoderm. This reduction in speed is accompanied by a similar reduction in the length of the spindle, thus ensuring that these two quantities are tightly linked. Using a combination of genetic and quantitative imaging approaches, we find that two processes contribute to controlling the speed at which chromosomes move at mitotic exit: the activity of molecular motors important for microtubule depolymerization and the cell cycle oscillator. Specifically, we found that the levels of Klp10A, Klp67A, and Klp59C, three kinesin-like proteins important for microtubule depolymerization, contribute to setting the speed of chromosome separation. This observation is supported by quantification of microtubule dynamics indicating that poleward flux rate scales with the length of the spindle. Perturbations of the cell cycle oscillator using heterozygous mutants of mitotic kinases and phosphatases revealed that the duration of anaphase increases during the blastoderm cycles and is the major regulator of chromosome velocity. Thus, our work suggests a potential link between the biochemical rate of mitotic exit and the forces exerted by the spindle. Collectively, we propose that the cell cycle oscillator and spindle length set the speed of chromosome separation in anaphase.
PubMed: 38948726
DOI: 10.1101/2024.06.17.598879