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1.
Bone Jt Open ; 5(9): 729-735, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39223986

ABSTRACT

Aims: Steroid injections are used for subacromial pain syndrome and can be administered via the anterolateral or posterior approach to the subacromial space. It is not currently known which approach is superior in terms of improving clinical symptoms and function. This is the protocol for a randomized controlled trial (RCT) to compare the clinical effectiveness of a steroid injection given via the anterolateral or the posterior approach to the subacromial space. Methods: The Subacromial Approach Injection Trial (SAInT) study is a single-centre, parallel, two-arm RCT. Participants will be allocated on a 1:1 basis to a subacromial steroid injection via either the anterolateral or the posterior approach to the subacromial space. Participants in both trial arms will then receive physiotherapy as standard of care for subacromial pain syndrome. The primary analysis will compare the change in Oxford Shoulder Score (OSS) at three months after injection. Secondary outcomes include the change in OSS at six and 12 months, as well as the Pain Numeric Rating Scale (0 = no pain, 10 = worst pain), Disabilities of Arm, Shoulder and Hand questionnaire (DASH), and 36-Item Short-Form Health Survey (SF-36) (RAND) at three months, six months, and one year after injection. Assessment of pain experienced during the injection will also be determined. A minimum of 86 patients will be recruited to obtain an 80% power to detect a minimally important difference of six points on the OSS change between the groups at three months after injection. Conclusion: The results of this trial will demonstrate if there is a difference in shoulder pain and function after a subacromial space steroid injection between the anterolateral versus posterior approach in patients with subacromial pain syndrome. This will help to guide treatment for patients with subacromial pain syndrome.

2.
AIDS Behav ; 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39249627

ABSTRACT

Children who are HIV-exposed and uninfected (CHEU) are at increased risk for poor growth, health, and development compared to children who are HIV-unexposed and uninfected. To support families with CHEU, we assessed the acceptability of engaging family members to support women living with HIV (WLWH) with exclusive breastfeeding (EBF) and antiretroviral therapy (ART) adherence and to engage in responsive infant caregiving. We conducted trials of improved practices, a consultative research approach, that follows participants over time as they try recommended behaviors. We enrolled postpartum women in Lusaka, Zambia, who identified home supporters. At visit 1, WLWH were interviewed about current practices. At visit 2, WLWH and home supporters received tailored EBF, responsive care, and ART adherence counseling. At visit 3, WLWH and home supporters were interviewed about their experiences trying recommended practices for 2-3 weeks. Interview transcripts were analyzed thematically. Participants included 23 WLWH, 15 male partners, and 8 female family members. WLWH reported several barriers to EBF. The most common were fear of HIV transmission via breastfeeding-despite high ART adherence-and insufficient breastmilk. After counseling, WLWH reported less fear of HIV transmission and improved breastfeeding practices. Home supporters reported providing WLWH increased support for EBF and ART adherence and practicing responsive caregiving. Both male and female home supporters appreciated being included in counseling and more involved in caregiving, and WLWH valued the increased support. Families with CHEU need focused support. Tailored counseling and family support for WLWH show promise for improving EBF, responsive caregiving, and ART adherence.

3.
BMC Plant Biol ; 24(1): 769, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39135189

ABSTRACT

BACKGROUND: Japanese knotweed (Reynoutria japonica var. japonica), a problematic invasive species, has a wide geographical distribution. We have previously shown the potential for attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy and chemometrics to segregate regional differentiation between Japanese knotweed plants. However, the contribution of environment to spectral differences remains unclear. Herein, the response of Japanese knotweed to varied environmental habitats has been studied. Eight unique growth environments were created by manipulation of the red: far-red light ratio (R: FR), water availability, nitrogen, and micronutrients. Their impacts on plant growth, photosynthetic parameters, and ATR-FTIR spectral profiles, were explored using chemometric techniques, including principal component analysis (PCA), linear discriminant analysis, support vector machines (SVM) and partial least squares regression. Key wavenumbers responsible for spectral differences were identified with PCA loadings, and molecular biomarkers were assigned. Partial least squared regression (PLSR) of spectral absorbance and root water potential (RWP) data was used to create a predictive model for RWP. RESULTS: Spectra from plants grown in different environments were differentiated using ATR-FTIR spectroscopy coupled with SVM. Biomarkers highlighted through PCA loadings corresponded to several molecules, most commonly cell wall carbohydrates, suggesting that these wavenumbers could be consistent indicators of plant stress across species. R: FR most affected the ATR-FTIR spectra of intact dried leaf material. PLSR prediction of root water potential achieved an R2 of 0.8, supporting the potential use of ATR-FTIR spectrometers as sensors for prediction of plant physiological parameters. CONCLUSIONS: Japanese knotweed exhibits environmentally induced phenotypes, indicated by measurable differences in their ATR-FTIR spectra. This high environmental plasticity reflected by key biomolecular changes may contribute to its success as an invasive species. Light quality (R: FR) appears critical in defining the growth and spectral response to environment. Cross-species conservation of biomarkers suggest that they could function as indicators of plant-environment interactions including abiotic stress responses and plant health.


Subject(s)
Phenotype , Spectroscopy, Fourier Transform Infrared/methods , Principal Component Analysis , Introduced Species , Plant Leaves/chemistry , Photosynthesis
4.
BMC Cardiovasc Disord ; 24(1): 409, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39103770

ABSTRACT

BACKGROUND: This study evaluated the effects of concurrent isolated training (T) or training combined with the antioxidant N-acetylcysteine (NAC) on cardiac remodeling and oxidative stress in spontaneously hypertensive rats (SHR). METHODS: Six-month-old male SHR were divided into sedentary (S, n = 12), concurrent training (T, n = 13), sedentary supplemented with NAC (SNAC, n = 13), and concurrent training with NAC supplementation (TNAC, n = 14) groups. T and TNAC rats were trained three times a week on a treadmill and ladder; NAC supplemented groups received 120 mg/kg/day NAC in rat chow for eight weeks. Myocardial antioxidant enzyme activity and lipid hydroperoxide concentration were assessed by spectrophotometry. Gene expression of NADPH oxidase subunits Nox2, Nox4, p22 phox, and p47 phox was evaluated by real time RT-PCR. Statistical analysis was performed using ANOVA and Bonferroni or Kruskal-Wallis and Dunn. RESULTS: Echocardiogram showed concentric remodeling in TNAC, characterized by increased relative wall thickness (S 0.40 ± 0.04; T 0.39 ± 0.03; SNAC 0.40 ± 0.04; TNAC 0.43 ± 0.04 *; * p < 0.05 vs T and SNAC) and diastolic posterior wall thickness (S 1.50 ± 0.12; T 1.52 ± 0.10; SNAC 1.56 ± 0.12; TNAC 1.62 ± 0.14 * mm; * p < 0.05 vs T), with improved contractile function (posterior wall shortening velocity: S 39.4 ± 5.01; T 36.4 ± 2.96; SNAC 39.7 ± 3.44; TNAC 41.6 ± 3.57 * mm/s; * p < 0.05 vs T). Myocardial lipid hydroperoxide concentration was lower in NAC treated groups (S 210 ± 48; T 182 ± 43; SNAC 159 ± 33 *; TNAC 110 ± 23 *# nmol/g tissue; * p < 0.05 vs S, # p < 0.05 vs T and SNAC). Nox 2 and p22 phox expression was higher and p47 phox lower in T than S [S 1.37 (0.66-1.66); T 0.78 (0.61-1.04) *; SNAC 1.07 (1.01-1.38); TNAC 1.06 (1.01-1.15) arbitrary units; * p < 0.05 vs S]. NADPH oxidase subunits did not differ between TNAC, SNAC, and S groups. CONCLUSION: N-acetylcysteine supplementation alone reduces oxidative stress in untreated spontaneously hypertensive rats. The combination of N-acetylcysteine and concurrent exercise further decreases oxidative stress. However, the lower oxidative stress does not translate into improved cardiac remodeling and function in untreated spontaneously hypertensive rats.


Subject(s)
Acetylcysteine , Hypertension , NADPH Oxidases , Oxidative Stress , Rats, Inbred SHR , Ventricular Remodeling , Animals , Male , Oxidative Stress/drug effects , Acetylcysteine/pharmacology , Ventricular Remodeling/drug effects , Hypertension/physiopathology , Hypertension/drug therapy , Hypertension/metabolism , NADPH Oxidases/metabolism , NADPH Oxidases/genetics , Rats , Antioxidants/pharmacology , Physical Conditioning, Animal , Disease Models, Animal , NADPH Oxidase 2/metabolism , NADPH Oxidase 2/genetics , NADPH Oxidase 4/metabolism , NADPH Oxidase 4/genetics , Membrane Glycoproteins/metabolism , Membrane Glycoproteins/genetics , Myocardium/metabolism , Myocardium/pathology , Lipid Peroxides/metabolism , Ventricular Function, Left/drug effects , Dietary Supplements , Hypertrophy, Left Ventricular/physiopathology , Hypertrophy, Left Ventricular/prevention & control , Hypertrophy, Left Ventricular/metabolism
5.
Analyst ; 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39105622

ABSTRACT

Lung cancer is one of the most commonly occurring malignant tumours worldwide. Although some reference methods such as X-ray, computed tomography or bronchoscope are widely used for clinical diagnosis of lung cancer, there is still a need to develop new methods for early detection of lung cancer. Especially needed are approaches that might be non-invasive and fast with high analytical precision and statistically reliable. Herein, we developed a swab "dip" test in saliva whereby swabs were analysed using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy harnessed to principal component analysis-quadratic discriminant analysis (QDA) and variable selection techniques employing successive projections algorithm (SPA) and genetic algorithm (GA) for feature selection/extraction combined with QDA. A total of 1944 saliva samples (56 designated as lung-cancer positive and 1888 designed as controls) were obtained in a lung cancer-screening programme being undertaken in North-West England. GA-QDA models achieved, for the test set, sensitivity and specificity values of 100.0% and 99.1%, respectively. Three wavenumbers (1422 cm-1, 1546 cm-1 and 1578 cm-1) were identified using the GA-QDA model to distinguish between lung cancer and controls, including ring C-C stretching, CN adenine, Amide II [δ(NH), ν(CN)] and νs(COO-) (polysaccharides, pectin). These findings highlight the potential of using biospectroscopy associated with multivariate classification algorithms to discriminate between benign saliva samples and those with underlying lung cancer.

6.
Health Res Policy Syst ; 22(1): 112, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39160603

ABSTRACT

BACKGROUND: Multi-drug-resistant tuberculosis (MDR-TB) infections are a public health concern. Since 2017, the Ministry of Health (MoH) in Zambia, in collaboration with its partners, has been implementing decentralised MDR-TB services to address the limited community access to treatment. This study sought to explore the role of collaboration in the implementation of decentralised multi drug-resistant tuberculosis services in Zambia. METHODS: A qualitative case study design was conducted in selected provinces in Zambia using in-depth and key informant interviews as data collection methods. We conducted a total of 112 interviews involving 18 healthcare workers, 17 community health workers, 32 patients and 21 caregivers in healthcare facilities located in 10 selected districts. Additionally, 24 key informant interviews were conducted with healthcare workers managers at facility, district, provincial, and national-levels. Thematic analysis was employed guided by the Integrative Framework for Collaborative Governance. FINDINGS: The principled engagement was shaped by the global health agenda/summit meeting influence on the decentralisation of TB, engagement of stakeholders to initiate decentralisation, a supportive policy environment for the decentralisation process and guidelines and quarterly clinical expert committee meetings. The factors that influenced the shared motivation for the introduction of MDR-TB decentralisation included actors having a common understanding, limited access to health facilities and emergency transport services, a shared understanding of challenges in providing optimal patient monitoring and review and their appreciation of the value of evidence-based decision-making in the implementation of MDR- TB decentralisation. The capacity for joint action strategies included MoH initiating strategic partnerships in enhancing MDR-TB decentralisation, the role of leadership in organising training of healthcare workers and of multidisciplinary teams, inadequate coordination, supervision and monitoring of laboratory services and joint action in health infrastructural rehabilitation. CONCLUSIONS: Principled engagement facilitated the involvement of various stakeholders, the dissemination of relevant policies and guidelines and regular quarterly meetings of clinical expert committees to ensure ongoing support and guidance. A shared motivation among actors was underpinned by a common understanding of the barriers faced while implementing decentralisation efforts. The capacity for joint action was demonstrated through several key strategies, however, challenges such as inadequate coordination, supervision and monitoring of laboratory services, as well as the need for collaborative efforts in health infrastructural rehabilitation were observed. Overall, collaboration has facilitated the creation of a more responsive and comprehensive TB care system, addressing the critical needs of patients and improving health outcomes.


Subject(s)
Health Personnel , Health Policy , Qualitative Research , Tuberculosis, Multidrug-Resistant , Humans , Zambia , Tuberculosis, Multidrug-Resistant/drug therapy , Politics , Stakeholder Participation , Health Services Accessibility/organization & administration , Delivery of Health Care/organization & administration , Cooperative Behavior , Community Health Workers/organization & administration , Female , Male
7.
Clin Transplant ; 38(9): e15439, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39190896

ABSTRACT

BACKGROUND: Living donor kidney transplantation is the optimal treatment for end-stage kidney disease; however, few living donor candidates (LDCs) who begin evaluation actually donate. While some LDCs are deemed medically ineligible, others discontinue for potentially modifiable reasons. METHODS: At five transplant centers, we conducted a prospective cohort study measuring LDCs' clinical and psychosocial characteristics, educational preparation, readiness to donate, and social determinants of health. We followed LDCs for 12 months after evaluation to determine whether they donated a kidney, opted to discontinue, had modifiable reasons for discontinuing, were medically ineligible, or had other recipient-related reasons for discontinuing. RESULTS: Among 2184 LDCs, 18.6% donated, 38.2% opted to or had modifiable reasons for discontinuing, and 43.2% were deemed ineligible due to medical or recipient-related reasons. Multivariable analyses comparing successful LDCs with those who did not complete donation for modifiable reasons (N = 1241) found that LDCs who discussed donation with the recipient before evaluation (OR, 2.31; 95% CI, 1.54-3.46), had completed high school (OR, 2.01; 95% CI, 1.21-3.35), or were a "close relation" to their recipient (OR, 1.89; 95% CI, 1.33-2.69) were more likely to donate. Conversely, LDCs who reported religion as important (OR, 0.55; 95% CI, 0.38-0.80), were Non-White (OR, 0.70; 95% CI, 0.49-1.00), or had overall higher anxiety scores (OR, 0.92; 95% CI, 0.86-0.99) were less likely to donate. CONCLUSION: With fewer than a fifth of LDCs donating, developing programs to provide greater emotional support and facilitate open discussions between LDCs and recipients earlier may increase living donation rates.


Subject(s)
Kidney Failure, Chronic , Kidney Transplantation , Living Donors , Humans , Living Donors/psychology , Living Donors/supply & distribution , Female , Male , Kidney Transplantation/psychology , Prospective Studies , Middle Aged , Follow-Up Studies , Prognosis , Adult , Kidney Failure, Chronic/surgery , Kidney Failure, Chronic/psychology , Tissue and Organ Procurement
8.
Sci Total Environ ; 951: 175687, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39173773

ABSTRACT

BACKGROUND: Wastewater monitoring data can be used to estimate disease trends to inform public health responses. One commonly estimated metric is the rate of change in pathogen quantity, which typically correlates with clinical surveillance in retrospective analyses. However, the accuracy of rate of change estimation approaches has not previously been evaluated. OBJECTIVES: We assessed the performance of approaches for estimating rates of change in wastewater pathogen loads by generating synthetic wastewater time series data for which rates of change were known. Each approach was also evaluated on real-world data. METHODS: Smooth trends and their first derivatives were jointly sampled from Gaussian processes (GP) and independent errors were added to generate synthetic viral load measurements; the range hyperparameter and error variance were varied to produce nine simulation scenarios representing different potential disease patterns. The directions and magnitudes of the rate of change estimates from four estimation approaches (two established and two developed in this work) were compared to the GP first derivative to evaluate classification and quantitative accuracy. Each approach was also implemented for public SARS-CoV-2 wastewater monitoring data collected January 2021-May 2023 at 25 sites in North Carolina, USA. RESULTS: All four approaches inconsistently identified the correct direction of the trend given by the sign of the GP first derivative. Across all nine simulated disease patterns, between a quarter and a half of all estimates indicated the wrong trend direction, regardless of estimation approach. The proportion of trends classified as plateaus (statistically indistinguishable from zero) for the North Carolina SARS-CoV-2 data varied considerably by estimation method but not by site. DISCUSSION: Our results suggest that wastewater measurements alone might not provide sufficient data to reliably track disease trends in real-time. Instead, wastewater viral loads could be combined with additional public health surveillance data to improve predictions of other outcomes.


Subject(s)
Wastewater , Wastewater/virology , COVID-19/epidemiology , North Carolina/epidemiology , Humans , Environmental Monitoring/methods , SARS-CoV-2 , Viral Load , Wastewater-Based Epidemiological Monitoring
9.
mBio ; : e0183424, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39194253

ABSTRACT

Chlamydia trachomatis has adapted to subvert signaling in epithelial cells to ensure successful intracellular development. Interferon-γ (IFNγ) produced by recruited lymphocytes signals through the JAK/STAT pathway to restrict chlamydial growth in the genital tract. However, during Chlamydia infection in vitro, addition of IFNγ does not fully induce nuclear localization of its transcription factor STAT1 and expression of its target gene, IDO1. We hypothesize that this altered interferon response is a result of Chlamydia targeting components of the IFNγ-JAK/STAT pathway. To assess the ability of replicating Chlamydia to dampen interferon signaling, HEp2 human epithelial cells were infected with C. trachomatis serovar L2 for 24 hours prior to exposure to physiologically relevant levels of IFNγ (500 pg/mL). This novel approach enabled us to observe reduced phospho-activation of both STAT1 and its kinase Janus Kinase 2 (JAK2) in infected cells compared with mock-infected cells. Importantly, basal JAK2 and STAT1 transcript and protein levels were dampened by infection even in the absence of interferon, which could have implications for cytokine signaling beyond IFNγ. Additionally, target genes IRF1, GBP1, APOL3, IDO1, and SOCS1 were not fully induced in response to IFNγ exposure. Infection-dependent decreases in transcript, protein, and phosphoprotein were rescued when de novo bacterial protein synthesis was inhibited with chloramphenicol, restoring expression of IFNγ-target genes. Similar Chlamydia-dependent dampening of STAT1 and JAK2 transcript levels was observed in infected HeLa and END1 endocervical cells and in HEp2s infected with C. trachomatis serovar D, suggesting a conserved mechanism of dampening the interferon response by reducing the availability of key signaling components. IMPORTANCE: As an obligate intracellular pathogen that has evolved to infect the genital epithelium, Chlamydia has developed strategies to prevent detection and antimicrobial signaling in its host to ensure its survival and spread. A major player in clearing Chlamydia infections is the inflammatory cytokine interferon-γ (IFNγ), which is produced by immune cells that are recruited to the site of infection. Reports of IFNγ levels in endocervical specimens from Chlamydia-infected patients range from 1 to 350 pg/mL, while most in vitro studies of the effects of IFNγ on chlamydial growth have used 15-85-fold higher concentrations. By using physiologically relevant concentrations of IFNγ, we were able to assess Chlamydia's ability to modulate its signaling. We found that Chlamydia decreases the expression of multiple components that are required for inducing gene expression by IFNγ, providing a possible mechanism by which Chlamydia trachomatis can attenuate the immune response in the female genital tract to cause long-term infections.

10.
Appl Environ Microbiol ; : e0029824, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39189736

ABSTRACT

We report the relationship between enrichment of adapted populations and enhancement of community functional resilience in methanogenic bioreactors. Although previous studies have shown the positive effects of acclimation, this work directly investigated the relationships between microbiome dynamics and performance of anaerobic co-digesting reactors in response to different levels of an environmental perturbation (loading of grease interceptor waste [GIW]). Using the methanogenic microbiome from a full-scale digester, we developed eight sets of microbial communities in triplicate using different feed sources. These substrate-specific microbiomes were then exposed to three independent disturbance events of low-, mid- and high-GIW loading rates. This approach allowed us to directly attribute differences in community responses to differences in community composition. Despite identical inocula, environment (digester operation, substrate loading rate, and feeding patterns) and general whole-community function (methane production and effluent quality) during the cultivation period, different substrates led to different microbial community assemblies. Lipid pre-acclimation led to enrichment of a pool of specialized populations, along with thriving of sub-dominant communities. The enrichment of these populations improved functional resilience and process performance when exposed to a low level of lipid-rich perturbation compared with less-acclimated communities. At higher levels of perturbation, the communities were not able to recover methanogenesis, indicating a loading limit to the resilience response. This study extends our current understanding of environmental perturbations, feed-specific adaptation, and functional resilience in methanogenic bioreactors.IMPORTANCEThis study demonstrates, for the first time for GIW co-digestion, how applying similar perturbations to different microbial communities was used to directly identify the causal relationships between microbial community, function, and environment in triplicate anaerobic microbiomes. We evaluated the impact of feed-specific adaptation on methanogenic microbiomes and demonstrated how microbiomes can be influenced to improve their functional (methanogenic) resilience to GIW inhibition. These findings demonstrate how an ecological framework can help improve a biological engineering application, and more specifically, increase the potential of anaerobic co-digestion for converting wastes to energy.

11.
J Am Chem Soc ; 146(35): 24330-24347, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39163519

ABSTRACT

Dynamic hydrogels are attractive platforms for tissue engineering and regenerative medicine due to their ability to mimic key extracellular matrix (ECM) mechanical properties like strain-stiffening and stress relaxation while enabling enhanced processing characteristics like injectability, 3D printing, and self-healing. Systems based on imine-type dynamic covalent chemistry (DCvC) have become increasingly popular. However, most reported polymers comprising aldehyde groups are based on either end-group-modified synthetic or side-chain-modified natural polymers; synthetic versions of side-chain-modified polymers are noticeably absent. To facilitate access to new classes of dynamic hydrogels, we report the straightforward synthesis of a water-soluble copolymer with a tunable fraction of pendant aldehyde groups (12-64%) using controlled radical polymerization and their formation into hydrogel biomaterials with dynamic cross-links. We found the polymer synthesis to be well-controlled with the determined reactivity ratios consistent with a blocky gradient microarchitecture. Subsequently, we observed fast gelation kinetics with imine-type cross-linking. We were able to vary hydrogel stiffness from ≈2 to 20 kPa, tune the onset of strain-stiffening toward a biologically relevant regime (σc ≈ 10 Pa), and demonstrate cytocompatibility using human dermal fibroblasts. Moreover, to begin to mimic the dynamic biochemical nature of the native ECM, we highlight the potential for temporal modulation of ligands in our system to demonstrate ligand displacement along the copolymer backbone via competitive binding. The combination of highly tunable composition, stiffness, and strain-stiffening, in conjunction with spatiotemporal control of functionality, positions these cytocompatible copolymers as a powerful platform for the rational design of next-generation synthetic biomaterials.


Subject(s)
Aldehydes , Biocompatible Materials , Hydrogels , Polymers , Hydrogels/chemistry , Hydrogels/chemical synthesis , Biocompatible Materials/chemistry , Biocompatible Materials/chemical synthesis , Ligands , Aldehydes/chemistry , Polymers/chemistry , Polymers/chemical synthesis , Humans
12.
Br J Ophthalmol ; 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39079892

ABSTRACT

BACKGROUND/AAIMS: Congenital stationary night blindness (CSNB) is an inherited retinal disease that is often associated with high myopia and can be caused by pathological variants in multiple genes, most commonly CACNA1F, NYX and TRPM1. High myopia is associated with retinal degeneration and increased risk for retinal detachment. Slowing the progression of myopia in patients with CSNB would likely be beneficial in reducing risk, but before interventions can be considered, it is important to understand the natural history of myopic progression. METHODS: This multicentre, retrospective study explored CSNB caused by variants in CACNA1F, NYX or TRPM1 in patients who had at least 6 measurements of their spherical equivalent of refraction (SER) before the age of 18. A mixed-effect model was used to predict progression of SER overtime and differences between genotypes were evaluated. RESULTS: 78 individuals were included in this study. All genotypes showed a significant myopic predicted SER at birth (-3.076D, -5.511D and -5.386D) for CACNA1F, NYX and TRPM1 respectively. Additionally, significant progression of myopia per year (-0.254D, -0.257D and -0.326D) was observed for all three genotypes CACNA1F, NYX and TRPM1, respectively. CONCLUSIONS: Patients with CSNB tend to be myopic from an early age and progress to become more myopic with age. Patients may benefit from long-term myopia slowing treatment in the future and further studies are indicated. Additionally, CSNB should be considered in the differential diagnosis for early-onset myopia.

13.
RSC Med Chem ; 15(7): 2300-2304, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39026655

ABSTRACT

Of the different modalities used to treat retinoblastoma, a chemothermotherapeutic regimen combining carboplatin and thermotherapy (also termed focal therapy), and the application of melphalan as a monotherapy, are particularly successful. Some studies indicate that melphalan shows potential when applied in combination with focal therapy, and yet is not applied in this combination. Here we describe a series of synthetically modified melphalan derivatives that display enhanced cytotoxicity relative to melphalan itself, with some displaying further enhancements in cytotoxicity when applied in combination with heat (used as a model for thermotherapy). The synthetic approach, which involves modifying melphalan with perfluorous chains of varying lengths via an ester linker, could lead to a more effective treatment option for retinoblastoma with reduced side-effects, which is a key limitation of melphalan.

14.
J Diabetes Metab Disord ; 23(1): 1293-1304, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38932812

ABSTRACT

Aim: This retrospective study aimed to use mixed (qualitative and quantitative) methods to evaluate the role of FSL in reducing hospital admissions due to all causes, HbA1c, and reported hypoglycaemic episodes in people with diabetes living in a socially deprived region of Northwest England. Methods: Data were collected retrospectively from previous consultations, which coincided with the 6th -week, 6th -month and annual review including blood tests, hospital admissions due to any cause and reported hypoglycaemia. Also, FSL assessment and satisfaction semi-structured questionnaire was done to assess the impact of FSL on diabetes management and quality of life. Mixed-effects models were used to assess glycaemic control and reductions in hospital admissions and reported hypoglycaemic episodes. Results: Just 127 patients met the inclusion criteria. A multivariate linear mixed model method that analyses HbA1c data longitudinally revealed mean differences (mmol/mol) between baseline and post-FSL measurements, estimated by restricted maximum likelihood method (REML) of 9.64 (six weeks), 7.68 (six months) and 7.58 (annual review); all with a corresponding p-value of < 0.0001. For DKA patients, the bootstrap method revealed a significant reduction in mean HbA1c of 25.5, 95% confidence interval (CI) [8.8, 42.6] mmol/mol. It is demonstrated that FSL use for one year resulted in 59% reduction in hospital admissions and 46% reduction in reported hypoglycaemic episodes. Conclusion: The use of FSL resulted in statistically significant reductions in hospital admissions, HbA1c and reported hypoglycaemic episodes among diabetics in a socially deprived Northwest region of England. These outcomes show a direct association with a higher questionnaire score. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01424-4.

15.
J Sch Psychol ; 105: 101314, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38876543

ABSTRACT

Teacher-student relationships are beneficial for students and especially important in the middle school context. Suspensions are critical to reduce as it can be detrimental to the educational trajectory of students, particularly for marginalized students in underfunded schools. This study looked at the relations between teacher-student relationships and suspensions across the academic year in a sample of students (N = 541) and teachers (N = 51) in two urban school districts in the Midwest. A brief measure of teachers' perceptions of relationships with students completed in the fall of the academic year predicted the odds of receiving in-school suspension (ISS; odds ratio [OR] = 0.65) and out-of-school suspension (OSS; OR = 0.72) by the end of the school year. Student reports of the relationships were also associated with ISS (OR = 0.94), but not OSS. On average, teachers' report on the scale improved over the course of the school year (d = 0.11); however, student report of the relationships worsened (d = 0.30). The difference in the student report of the relationships from fall to spring was also associated with the odds of receiving ISS and OSS (ORs = 0.94). These findings suggest that student and teacher perceptions together are associated with harsh discipline practices that can negatively impact students' developmental trajectories. Relationships can change but direct action is necessary to develop, maintain, and repair relationships during the academic year.


Subject(s)
Interpersonal Relations , School Teachers , Schools , Students , Humans , Students/psychology , School Teachers/psychology , Female , Male , Child , Adolescent , Punishment/psychology
17.
Waste Manag ; 186: 77-85, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38865907

ABSTRACT

A key question in anaerobic microbial ecology is how microbial communities develop over different stages of waste decomposition and whether these changes are specific to waste types. We destructively sampled over time 26 replicate bioreactors cultivated on fruit/vegetable waste (FVW) and meat waste (MW) based on pre-defined waste components and composition. To characterize community shifts, we examined 16S rRNA genes from both the leachate and solid fractions of the waste. Waste decomposition occurred faster in FVW than MW, as accumulation of ammonia in MW reactors led to inhibition of methanogenesis. We identified population succession during different stages of waste decomposition and linked specific populations to different waste types. Community analyses revealed underrepresentation of methanogens in the leachate fractions, emphasizing the importance of consistent and representative sampling when characterizing microbial communities in solid waste.


Subject(s)
Bioreactors , RNA, Ribosomal, 16S , Bioreactors/microbiology , Anaerobiosis , RNA, Ribosomal, 16S/genetics , Refuse Disposal/methods , Solid Waste/analysis , Bacteria/metabolism , Bacteria/genetics , Bacteria/classification , Vegetables/microbiology , Methane/metabolism , Fruit/microbiology , Garbage , Food Loss and Waste
19.
Ecotoxicol Environ Saf ; 278: 116390, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38705037

ABSTRACT

Microplastics (MPs) and benzo[a]pyrene (B[a]P) are prevalent environmental pollutants. Numerous studies have extensively reported their individual adverse effects on organisms. However, the combined effects and mechanisms of exposure in mammals remain unknown. Thus, this study aims to investigate the potential effects of oral administration of 0.5µm polystyrene (PS) MPs (1 mg/mL or 5 mg/mL), B[a]P (1 mg/mL or 5 mg/mL) and combined (1 mg/mL or 5 mg/mL) on 64 male SD rats by gavage method over 6-weeks. The results demonstrate that the liver histopathological examination showed that the liver lobules in the combined (5 mg/kg) group had blurred and loose boundaries, liver cord morphological disorders, and significant steatosis. The levels of AST, ALT, TC, and TG in the combined dose groups were significantly higher than those in the other groups, the combined (5 mg/kg) group had the lowest levels of antioxidant enzymes and the highest levels of oxidants. The expression of Nrf2 was lowest and the expression of P38, NF-κB, and TNF-α was highest in the combined (5 mg/kg) group. In conclusion, these findings indicate that the combination of PSMPs and B[a]P can cause the highest levels of oxidative stress and elicit markedly enhanced toxic effects, which cause severe liver damage.


Subject(s)
Benzo(a)pyrene , Liver , Microplastics , Oxidative Stress , Polystyrenes , Rats, Sprague-Dawley , Animals , Oxidative Stress/drug effects , Benzo(a)pyrene/toxicity , Microplastics/toxicity , Male , Polystyrenes/toxicity , Liver/drug effects , Liver/pathology , Rats , Environmental Pollutants/toxicity , Antioxidants/metabolism , NF-kappa B/metabolism , NF-E2-Related Factor 2/metabolism
20.
Ecol Evol ; 14(5): e11453, 2024 May.
Article in English | MEDLINE | ID: mdl-38774143

ABSTRACT

Cultivation of the mass-flowering crop oilseed rape (OSR), Brassica napus, can provide insects with super-abundant nectar and pollen while in bloom. Several authors have suggested breeding cultivars to produce more abundant nectar and pollen to help mitigate insect decline. However, in Britain most, 95%, OSR blooms in spring (March-May), which has been suggested to be a period of nectar surplus and reduced exploitative competition. Therefore, a large proportion of floral resources produced by OSR during this period may be uncollected. Although there has been extensive work examining OSR nectar and pollen production, no study, to our knowledge, has measured this in relation to the demand by the flower-visiting insects. Here we quantified the percentage of nectar produced by spring blooming OSR which was uncollected in four OSR fields per year over 2 years. This was achieved by measuring the nectar in both insect accessible and inaccessible (i.e. mesh-covered) flowers. We also quantified uncollected pollen in flowers at the beginning and the end of anthesis using a haemocytometer. Most of the nectar (69%) and a fifth of pollen (19%) was uncollected in spring blooming OSR. Based on the estimates of nectar production and observed number of insects, nectar supply per insect was estimated at 2204 µL nectar insect-1 h-1, which exceeds potential collection rates by flower-visiting insects. Given the majority of B. napus is spring blooming, breeding cultivars of OSR which produce more nectar, while not being detrimental to flower-visiting insects, may be of little conservation benefit.

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