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Locus Coeruleus Degeneration Differs Between Frontotemporal Lobar Degeneration Subtypes

J Alzheimers Dis. 2022 Jul 20. doi: 10.3233/JAD-220276. Online ahead of print.

ABSTRACT

BACKGROUND: There are few studies on the locus coeruleus (LC) in frontotemporal lobar degeneration (FTLD) and the potential differences in the LC related to the underlying proteinopathy.

OBJECTIVE: The aim of this study was to investigate the LC in FTLD subgroups.

METHODS: Neuropathological cases diagnosed with FTLD were included. The subgroups consisted of FTLD with tau, transactive response DNA-binding protein 43 (TDP) and fused in sarcoma (FUS). Micro- and macroscopical degeneration of the LC were assessed with respect to the number of neurons and the degree of depigmentation. A group of cognitively healthy subjects and a group with vascular cognitive impairment (VCI) served as comparison groups.

RESULTS: A total of 85 FTLD cases were included, of which 44 had FTLD-TDP, 38 had FTLD-tau, and three had FTLD-FUS. The groups were compared with 25 VCI cases and 41 cognitively healthy control cases (N = 151 for the entire study). All FTLD groups had a statistically higher microscopical degeneration of the LC compared to the controls, but the FTLD-tau group had greater micro- and macroscopical degeneration than the FTLD-TDP group. Age correlated positively with the LC score in the FTLD-tau group, but not in the FTLD-TDP group.

CONCLUSION: A greater microscopical degeneration of the LC was observed in all FTLD cases compared to healthy controls and those with VCI. The LC degeneration was more severe in FTLD-tau than in FTLD-TDP. The macroscopically differential degeneration of the LC in FTLD subgroups may facilitate differential diagnostics, potentially with imaging.

PMID:35871340 | DOI:10.3233/JAD-220276

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Identification of urinary biomarkers of colorectal cancer: Towards the development of a colorectal screening test in limited resource settings

Cancer Biomark. 2022 Jul 11. doi: 10.3233/CBM-220034. Online ahead of print.

ABSTRACT

BACKGROUND: African colorectal cancer (CRC) rates are rising rapidly. A low-cost CRC screening approach is needed to identify CRC from non-CRC patients who should be sent for colonoscopy (a scarcity in Africa).

OBJECTIVE: To identify urinary metabolite biomarkers that, combined with easy-to-measure clinical variables, would identify patients that should be further screened for CRC by colonoscopy. Ideal metabolites would be water-soluble and easily translated into a sensitive, low-cost point-of-care (POC) test.

METHODS: Liquid-chromatography mass spectrometry (LC-MS/MS) was used to quantify 142 metabolites in spot urine samples from 514 Nigerian CRC patients and healthy controls. Metabolite concentration data and clinical characteristics were used to determine optimal sets of biomarkers for identifying CRC from non-CRC subjects.

RESULTS: Our statistical analysis identified N1, N12-diacetylspermine, hippurate, p-hydroxyhippurate, and glutamate as the best metabolites to discriminate CRC patients via POC screening. Logistic regression modeling using these metabolites plus clinical data achieved an area under the receiver-operator characteristic (AUCs) curves of 89.2% for the discovery set, and 89.7% for a separate validation set.

CONCLUSIONS: Effective urinary biomarkers for CRC screening do exist. These results could be transferred into a simple, POC urinary test for screening CRC patients in Africa.

PMID:35871322 | DOI:10.3233/CBM-220034

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Are there differences between a real C0-C1 mobilization and a sham technique in function and pressure pain threshold in patients with chronic neck pain and upper cervical restriction? A randomised controlled clinical trial

J Back Musculoskelet Rehabil. 2022 Jul 12. doi: 10.3233/BMR-220008. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic neck pain is one of the main reasons for visiting a healthcare professional. In recent years, it has been shown that upper cervical restriction may be a factor involved in neck pain.

OBJECTIVE: To compare the immediate effects of a real cervical mobilization technique versus a sham cervical mobilization technique in patients with chronic neck pain and upper cervical restriction.

METHODS: This was a randomised, controlled, double-blind clinical trial. Twenty-eight patients with chronic neck pain were recruited and divided into two groups (14 = real cervical mobilization; 14 = sham mobilization). Both groups received a single 5-minute treatment session. Upper cervical range motion, flexion-rotation test, deep cervical activation and pressure pain threshold were measured.

RESULTS: In the between-groups comparison, statistically significant differences were found in favour of the real cervical mobilization group in upper cervical extension (p= 0.003), more restricted side of flexion-rotation test (p< 0.001) and less restricted side of flexion-rotation test (p= 0.007) and in the pressure pain threshold of the right trapezius (p= 0.040) and right splenius (p= 0.049). No differences in deep muscle activation were obtained.

CONCLUSION: The real cervical mobilization group generates improvements in upper cervical spine movement and pressure pain threshold of right trapezius and right splenius compared to the sham group in patients with chronic neck pain and upper cervical restriction.

PMID:35871321 | DOI:10.3233/BMR-220008

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Acupoints sensitization in people with and without chronic low back pain:A matched-sample cross-sectional study

J Back Musculoskelet Rehabil. 2022 Jul 11. doi: 10.3233/BMR-210297. Online ahead of print.

ABSTRACT

BACKGROUND: Acupoints are considered a dynamic functional area, which can reflect the internal condition of the body. In pathological states, disease-related acupoints are believed to be activated, which is known as acupoint sensitization.

OBJECTIVE: This study aimed to investigate the major manifestations of acupoint sensitization in patients with chronic low back pain (cLBP) to provide better understanding of acupoint sensitization phenomena in the context of cLBP.

METHODS: This study was a matched-sample cross-sectional study 16 participants diagnosed with cLBP and 16 healthy controls matched in age, sex, and ethnicity were included. The following aspects of sensitization phenomena of targeted points were compared: pressure pain threshold (PPT), skin temperature, surface electrical conductance, receptive field, and morphological change of skin.

RESULTS: PPT at points of interest were significantly lower in cLBP participants compared with healthy controls (P< 0.05); in addition, receptive field was found to be larger at left BL 23 in cLBP participants (P< 0.05). There was no statistically significant difference in skin temperature, electrical conductance, or morphology between the two groups.

CONCLUSIONS: Reduced PPT at all detected points and enlarged receptive field at left BL 23 were found in cLBP participants. These two features appear key in defining acupoint sensitization in cLBP, and provide evidence for selecting and locating acupuncture points in future clinical studies.

PMID:35871318 | DOI:10.3233/BMR-210297

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A comparative study of clinical leadership needs analysis (CLeeNa) as perceived by nurses

J Clin Nurs. 2022 Jul 24. doi: 10.1111/jocn.16089. Online ahead of print.

ABSTRACT

AIMS: This study aimed to analyse nurses’ perceptions of clinical leadership needs and compare their differences based on the sample’s characteristics. Also, it aimed to compare nurses’ perceptions of clinical leadership needs between nurses and nurse managers.

BACKGROUND: Various professional organisations have identified the need to develop clinical leaders. Clinical leadership is about having clinical expertise in specialised fields and having professionals involved in clinical care. However, worldwide, little emphasis is placed on the clinical leadership needs of nurses.

METHODS: Using STROBE (https://www.strobe-statement.org/index.php?id=available-checklists), a cross-sectional study was conducted in 2020 using a purposive sample of 349 Jordanian nurses who were surveyed using the CLeeNA instrument. Different descriptive and inferential statistics were used to analyse the data. The response rate in the current study was 69.8%.

RESULTS: The 7-point CleeNa scale was reduced into 3 categories 1 = “not important (1-3),” 2 = “Neutral (4)” and 3 = “highly important (5-7).” The total mean score of perceived CleeNa was 2.61(SD = 0.50) indicating “very important.” The highest perceived mean score of the subscales was for “leadership and clinical practice.” In contrast, the lowest perceived mean score of the subscales was “financial and service management.” The total mean scores of perceived CleeNa were higher among married nurses, nurse managers, those who have a master degree or more, aged 35 years or more, had more than 4 years of nursing experience or/and more than 4 years of leadership experience, supervised more than 10 employees and were working in teaching hospitals. The total mean scores of perceived CleeNa scale and subscales of staff and team development, patient safety and risk management, and perceived standards of care were higher among nurse managers when compared with nurses.

CONCLUSION AND RELEVANCE TO CLINICAL PRACTICE: Results indicated that innovative clinical leaders are needed. A paucity of research identifies the extent to which clinical leadership is enacted in clinical nursing practice. Developing a clinical leadership programme is warranted to contribute positively to nurses’ leadership roles and outcomes, patients’ outcomes, and in turn, organisational outcomes.

PMID:35871294 | DOI:10.1111/jocn.16089

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Saliva as alternative to naso-oropharyngeal swab for SARS-CoV-2 detection by RT-qPCR: a multicenter cross-sectional diagnostic validation study

Sci Rep. 2022 Jul 23;12(1):12612. doi: 10.1038/s41598-022-16849-1.

ABSTRACT

Saliva has been demonstrated as feasible alternative to naso-oropharyngeal swab (NOS) for SARS-CoV-2 detection through reverse transcription quantitative/real-time polymerase chain reaction (RT-qPCR). This study compared the diagnostic agreement of conventional NOS, saliva with RNA extraction (SE) and saliva without RNA extraction (SalivaDirect) processing for RT-qPCR in identifying SARS-CoV-2. All techniques were also compared, as separate index tests, to a composite reference standard (CRS) where positive and negative results were defined as SARS-CoV-2 detection in either one or no sample, respectively. Of 517 paired samples, SARS-CoV-2 was detected in 150 (29.01%) NOS and 151 (29.21%) saliva specimens. The saliva-based tests were noted to have a sensitivity, specificity and accuracy (95% confidence interval) of 92.67% (87.26%, 96.28%), 97.55% (95.40%, 98.87%) and 96.13% (94.09%, 97.62%), respectively, for SE RT-qPCR and 91.33% (85.64%, 95.30%), 98.91% (97.23%, 99.70%) and 96.71% (94.79%, 98.07%), respectively, for SalivaDirect RT-qPCR compared to NOS RT-qPCR. Compared to CRS, all platforms demonstrated statistically similar diagnostic performance. These findings suggest that both conventional and streamlined saliva RT-qPCR are at least non-inferior to conventional NOS RT-qPCR in detecting SARS-CoV-2.

PMID:35871257 | DOI:10.1038/s41598-022-16849-1

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Somatic mutations in DCC are associated with genomic instability and favourable outcomes in melanoma patients treated with immune checkpoint inhibitors

Br J Cancer. 2022 Jul 23. doi: 10.1038/s41416-022-01921-4. Online ahead of print.

ABSTRACT

BACKGROUND: Deleted in colorectal cancer (DCC) encodes a transmembrane dependence receptor and is frequently mutated in melanoma. The associations of DCC mutation with chromosomal instability and immunotherapeutic efficacy in melanoma are largely uncharacterised.

METHODS: We performed an integrated study based on biological experiments and multi-dimensional data types, including genomic, transcriptomic and clinical immune checkpoint blockade (ICB)-treated melanoma cohorts from public databases.

RESULTS: DCC mutation was significantly correlated with the tumour mutational burden (TMB) in The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and ICB-treated melanoma cohorts. DCC expression levels were correlated with DNA damage response and repair (DDR) pathways responsive to irradiation (IR) in the Malme-3M and SK-MEL-2 cell lines. In the TCGA cohort, DCC-mutated samples presented more neoantigens, higher proportions of infiltrating antitumour immunocytes and lower proportions of infiltrating pro-tumour immunocytes than DCC wild-type samples. DCC-mutated samples were significantly enriched in activated immune response and DDR pathways. Furthermore, patients harbouring mutated DCC treated with ICB showed remarkable clinical benefits in terms of the response rate and overall survival.

CONCLUSIONS: Somatic mutations in DCC are associated with improved clinical outcomes in ICB-treated melanoma patients. Once further validated, the DCC mutational status can improve patient selection for clinical practice and future study enrolment.

PMID:35871235 | DOI:10.1038/s41416-022-01921-4

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Predicting suitable habitats of Melia azedarach L. in China using data mining

Sci Rep. 2022 Jul 23;12(1):12617. doi: 10.1038/s41598-022-16571-y.

ABSTRACT

Melia azedarach L. is an important economic tree widely distributed in tropical and subtropical regions of China and some other countries. However, it is unclear how the species’ suitable habitat will respond to future climate changes. We aimed to select the most accurate one among seven data mining models to predict the current and future suitable habitats for M. azedarach in China. These models include: maximum entropy (MaxEnt), support vector machine (SVM), generalized linear model (GLM), random forest (RF), naive bayesian model (NBM), extreme gradient boosting (XGBoost), and gradient boosting machine (GBM). A total of 906 M. azedarach locations were identified, and sixteen climate predictors were used for model building. The models’ validity was assessed using three measures (Area Under the Curves (AUC), kappa, and overall accuracy (OA)). We found that the RF provided the most outstanding performance in prediction power and generalization capacity. The top climate factors affecting the species’ suitable habitats were mean coldest month temperature (MCMT), followed by the number of frost-free days (NFFD), degree-days above 18 °C (DD > 18), temperature difference between MWMT and MCMT, or continentality (TD), mean annual precipitation (MAP), and degree-days below 18 °C (DD < 18). We projected that future suitable habitat of this species would increase under both the RCP4.5 and RCP8.5 scenarios for the 2011-2040 (2020s), 2041-2070 (2050s), and 2071-2100 (2080s). Our findings are expected to assist in better understanding the impact of climate change on the species and provide scientific basis for its planting and conservation.

PMID:35871227 | DOI:10.1038/s41598-022-16571-y

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Impact of elevated systolic arterial pulmonary pressure on the total mortality rate after acute myocardial infarction in the elderly

Sci Rep. 2022 Jul 23;12(1):12626. doi: 10.1038/s41598-022-16210-6.

ABSTRACT

Reduced left ventricular ejection fraction (LVEF) is associated with increased mortality after acute myocardial infarction (AMI). However, the prognostic impact of elevated systolic pulmonary artery pressure (sPAP) in the very elderly patients after AMI is lacking. We aimed to study the impact of elevated sPAP on one- and five-year all-cause mortality after AMI in very elderly patients, 80 years of age and older. Of a total number of 353 patients (≥ 80 years) who were hospitalized with acute coronary syndrome, 162 patients presenting with AMI and with available data of sPAP on echocardiography were included and followed-up for 5 years. The survival analyses were performed using Cox-Regression models adjusted for conventional risk factors including LVEF. Altogether 66 of 162 patients (41%) had ST-segment elevation MI, and 121 (75%) of patients were treated with percutaneous coronary intervention in the acute phase. Echocardiography during the admission revealed that 78 patients (48%) had a LVEF ≤ 45% and 66 patients (41%) had a sPAP ≥ 40 mmHg. After one and five years of follow-up, 23% (n = 33) and 53% (n = 86) of patients died, respectively. A multivariable Cox-Regression analysis showed that the elevated sPAP (≥ 40 mmHg) was an independent predictor of increased mortality in both one and five years after AMI; HR of 2.63 (95%, CI 1.19-5.84, P 0.017) and HR of 2.08 (95%, CI 1.25-3.44, P 0.005) respectively, whereas LVEF ≤ 45% did not show any statistically significant impact, neither on one- nor on five-year mortality (HR 1.3, 95% CI 0.6-2.9, p = 0.469) and (HR 1.4, 95% CI 0.8-2.4, p = 0.158), respectively. Elevated sPAP was an independent risk factor for one- and five-year all-cause mortality after AMI in very elderly patients and sPAP seems to be a better prognostic predictor for all-cause mortality than LVEF. The risk of all-cause mortality after AMI increased with increasing sPAP.

PMID:35871222 | DOI:10.1038/s41598-022-16210-6

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Consonant Age of Acquisition Reveals Nonlinear Effects in Nonword Repetition Performance

J Psycholinguist Res. 2022 Jul 23. doi: 10.1007/s10936-022-09901-8. Online ahead of print.

ABSTRACT

Recent work has shown significant sublexical effects of long-term memory in nonword repetition (NWR) using a dichotomous consonant age of acquisition (CAoA) variable (Moore, 2018; Moore, Fiez, and Tompkins, 2017). Performance consistently decreased when stimuli comprised consonants acquired later versus earlier in speech development. To address potential confounds related to stimulus design and linearity, the purpose of this study was to test whether performance decreases as the CAoA value of stimuli increases in various linguistic tasks using a continuous CAoA variable. Thirty-one college students completed NWR and other linguistic tasks in which the stimuli varied in average CAoA values. Data were analyzed using multilevel modeling. After accounting for phonotactic probability, CAoA was a statistically significant predictor of performance across the models reported. The relationship was more complex in some of the models in which CAoA showed a statistically significant nonlinear relationship with the outcome measure. Results from this study support previous work showing that CAoA affects performance on NWR and other linguistic tasks that vary in their memory, auditory perceptual, and articulatory demands. Importantly, this line of work was extended here by demonstrating that the CAoA effect is robust across novel stimulus sets and study designs, and may be more complex than previously understood when using a dichotomous CAoA variable. Quadratic results suggest that the CAoA variable has a differential effect on performance for low to moderate CAoA values, but for higher CAoA values the effect is similarly negative. The nonlinear relationship between CAoA and measures of speed and accuracy on some of the tasks warrants further study into the complex relationship between various predictive factors that contribute to language performance.

PMID:35871210 | DOI:10.1007/s10936-022-09901-8