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1.
J Clin Med ; 13(7)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38610914

RESUMO

Background: Forward head posture (FHP) and altered cervical lordotic curvatures are common spine displacements often associated with neck pain and disability. Two primary categories for determining FHP exist: radiographic and postural measurements. Methods: This study investigated the correlation between the craniovertebral angle (CVA), the radiographically measured C2-C7 sagittal vertical axis (SVA), and cervical lordosis (absolute rotation angle: ARA C2-C7) in a sample of participants with chronic myofascial pain (CMP). In 120 participants, we performed both a postural measurement of the CVA and a lateral cervical radiograph, where the C2-C7 SVA and ARA C2-C7 were measured. A linear-regression R2 value to assess the correlation between the CVA, C2-C7 SVA, and ARA C2-C7 was sought. Results: A statistically significant weak linear fit was identified (Spearman's r = 0.549; R2 = 0.30, p < 0.001) between the CVA and C2-C7 SVA, having considerable variation between the two measures. A statistically significant linear fit (very weak) was identified for the lordosis ARA C2-C7 and the CVA: Spearman's r = 0.524; R2 = 0.275; p < 0.001. A value of 50° for the CVA corresponded to a value of 20 mm for the C2-C7 SVA on an X-ray. Conclusion: While the CVA and radiographic C2-C7 SVA are weakly correlated in an individual, they seem to represent different aspects of sagittal cervical balance. The CVA cannot replace radiographically measured cervical lordosis. We recommend that more emphasis be given to radiographic measures of sagittal cervical alignment than the CVA when considering patient interventions.

2.
Microbiol Spectr ; 12(3): e0499822, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38334387

RESUMO

Multiple vaccines have been developed and licensed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). While these vaccines reduce disease severity, they do not prevent infection. To prevent infection and limit transmission, vaccines must be developed that induce immunity in the respiratory tract. Therefore, we performed proof-of-principle studies with an intranasal nanoparticle vaccine against SARS-CoV-2. The vaccine candidate consisted of the self-assembling 60-subunit I3-01 protein scaffold covalently decorated with the SARS-CoV-2 receptor-binding domain (RBD) using the SpyCatcher-SpyTag system. We verified the intended antigen display features by reconstructing the I3-01 scaffold to 3.4 A using cryogenicelectron microscopy. Using this RBD-grafted SpyCage scaffold (RBD + SpyCage), we performed two intranasal vaccination studies in the "gold-standard" pre-clinical Syrian hamster model. The initial study focused on assessing the immunogenicity of RBD + SpyCage combined with the LTA1 intranasal adjuvant. These studies showed RBD + SpyCage vaccination induced an antibody response that promoted viral clearance but did not prevent infection. Inclusion of the LTA1 adjuvant enhanced the magnitude of the antibody response but did not enhance protection. Thus, in an expanded study, in the absence of an intranasal adjuvant, we evaluated if covalent bonding of RBD to the scaffold was required to induce an antibody response. Covalent grafting of RBD was required for the vaccine to be immunogenic, and animals vaccinated with RBD + SpyCage more rapidly cleared SARS-CoV-2 from both the upper and lower respiratory tract. These findings demonstrate the intranasal SpyCage vaccine platform can induce protection against SARS-CoV-2 and, with additional modifications to improve immunogenicity, is a versatile platform for the development of intranasal vaccines targeting respiratory pathogens.IMPORTANCEDespite the availability of efficacious COVID vaccines that reduce disease severity, SARS-CoV-2 continues to spread. To limit SARS-CoV-2 transmission, the next generation of vaccines must induce immunity in the mucosa of the upper respiratory tract. Therefore, we performed proof-of-principle, intranasal vaccination studies with a recombinant protein nanoparticle scaffold, SpyCage, decorated with the RBD of the S protein (SpyCage + RBD). We show that SpyCage + RBD was immunogenic and enhanced SARS-CoV-2 clearance from the nose and lungs of Syrian hamsters. Moreover, covalent grafting of the RBD to the scaffold was required to induce an immune response when given via the intranasal route. These proof-of-concept findings indicate that with further enhancements to immunogenicity (e.g., adjuvant incorporation and antigen optimization), the SpyCage scaffold has potential as a versatile, intranasal vaccine platform for respiratory pathogens.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Animais , Cricetinae , Humanos , Mesocricetus , 60547 , SARS-CoV-2 , COVID-19/prevenção & controle , Anticorpos Antivirais , Anticorpos Neutralizantes
3.
J Clin Med ; 13(3)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38337607

RESUMO

Background: Neurodynamic exercise is a common clinical practice used to restore neural dynamic balance. The order in which movements are performed during these exercises is believed to play a crucial role in their effectiveness. This study aimed to investigate the impact of different sequences of neurodynamic exercise on nerve root function, with a specific focus on the median nerve. Methods: Participants were assigned randomly to three experimental groups, each undergoing a different test sequence: standard, proximal-to-distal, and distal-to-proximal. Dermatomal somatosensory evoked potentials (DSSEPs) were recorded at key levels (C6, C7, C8, and T1). Results: The findings revealed a significant influence of the movement sequence on DSSEP amplitudes. The execution of neurodynamic exercise in the proximal-to-distal sequence was associated with a notable reduction in amplitudes (p < 0.05). Conversely, the distal-to-proximal sequence resulted in increased amplitudes compared to the standard sequence (p < 0.05). Conclusions: This study underscores the importance of carefully considering the order of movements during neurodynamic exercising, particularly when evaluating nerve roots that lack the protective perineurium. The choice of sequence appears to have a substantial impact on nerve function, with implications for optimizing clinical neurodynamic exercise techniques.

4.
J Clin Med ; 12(19)2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37834858

RESUMO

This study assessed the relationship between head posture displacements and biomechanical parameters during gait and jumping. One hundred male and female students (20 ± 3 yrs) were assessed via the PostureScreen Mobile® app to quantify postural displacements of head rotations and translations including: (1) the cranio-vertebral angle (CVA) (°), (2) anterior head translation (AHT) (cm), (3) lateral head translation in the coronal plane (cm), and (4) lateral head side bending (°). Biomechanical parameters during gait and jumping were measured using the G-Walk sensor. The assessed gait spatiotemporal parameters were cadence (steps/min), speed (m/s), symmetry index, % left and right stride length (% height), and right and left propulsion index. The pelvic movement parameters were (1) tilt symmetry index, (2) tilt left and right range, (3) obliquity symmetry index, (4) obliquity left and right range, (5) rotation symmetry index, and (6) rotation left and right range. The jump parameters measured were (1) flight height (cm), (2) take off force (kN), (3) impact Force (kN), (4) take off speed (m/s), (5) peak speed (m/s), (6) average speed concentric phase (m/s), (7) maximum concentric power (kW), (8) average concentric power (kW) during the counter movement jump (CMJ), and (9) CMJ with arms thrust (CMJAT). At a significance level of p ≤ 0.001, moderate-to-high correlations (0.4 < r < 0.8) were found between CVA, AHT, lateral translation head, and all the gait and jump parameters. Weak correlations (0.2 < r < 0.4) were ascertained for lateral head bending and all the gait and jump parameters except for gait symmetry index and pelvic symmetry index, where moderate correlations were identified (0.4 < r < 0.6). The findings indicate moderate-to-high correlations between specific head posture displacements, such as CVA, lateral head translation and AHT with the various gait and jump parameters. These findings highlight the importance of considering head posture in the assessment and optimization of movement patterns during gait and jumping. Our findings contribute to the existing body of knowledge and may have implications for clinical practice and sports performance training. Further research is warranted to elucidate the underlying mechanisms and establish causality in these relationships, which could potentially lead to the development of targeted interventions for improving movement patterns and preventing injuries.

5.
J Clin Med ; 12(17)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37685669

RESUMO

Spinal injuries, disorders and disabilities are among the leading causes for work loss, suffering, and health care expenditures throughout the industrialized world [...].

6.
J Clin Med ; 12(14)2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37510736

RESUMO

This study assessed the relationship between body posture displacements, cardiopulmonary exercise testing (CPET), and skill-related physical fitness tests. One hundred male (60%) and female collegiate athletes (22.2 ± 4 yrs) with normal body mass indexes (BMI up to 24.9) were assessed via the PostureScreen Mobile® app to quantify postural displacements such as head, thorax, and pelvis rotations and translations. CPET and physical performance tests, including the agility t-test, vertical jump test, stork static balance test (SSBT), and dynamic Y-balance test (YBT), were performed. Spearman correlation (r) and p-values are reported. The postural parameters were found to have moderate-to-high associations with the CPET and agility test, moderate correlations with the vertical jump test and SSBT (head and pelvic postures only), and weak correlations with the YBT. As the postural parameters were more asymmetric, both the CPET and performance skills scores were worse. For example: (1) a medium positive correlation was found between cranio-vertebral angle (CVA) and the vertical jump test (r = 0.54; p-value < 0.001) and SSBT (r = 0.57; p-value < 0.001), while a strong negative correlation was found between CVA and the agility test (r = -0.86; p-value < 0.001). (2) A strong positive correlation was found between CVA and oxygen uptake efficiency slope, load watts VO2 at VT, VO2/kg, and load watts at the respiratory compensation point (RCP) (r = 0.65 and r = 0.71; p < 0.001). Conversely, a significant negative correlation was found between CVA and VE/VO2 at VT (r = -0.61; p < 0.001). Postural rotations and translations of the head, thorax, and pelvis were statistically correlated with the physical performance skills and CPET in the young collegiate athletes. There were moderate-to-high associations with cardiopulmonary functions and the agility tests, moderate correlations with the vertical jump test, and weak correlations with the YBT. Postural alignment may be important for optimal physical performance and optimal cardiopulmonary function. Further research is necessary to elucidate the reasons for these correlations found in our sample of young and healthy athletes.

7.
J Clin Med ; 12(11)2023 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-37297903

RESUMO

There is great interest in thoracic kyphosis, as it is thought to be a contributor to neck pain, neck disability, and sensorimotor control measures; however, this has not been completely investigated in treatment or case control studies. This case control design investigated participants with non-specific chronic neck pain. Eighty participants with a defined hyper-kyphosis (>55°) were compared to eighty matched participants with normal thoracic kyphosis (<55°). Participants were matched for age and neck pain duration. Hyper-kyphosis was further categorized into two distinct types: postural kyphosis (PK) and Scheuermann's kyphosis (SK). Posture measures included formetric thoracic kyphosis and the craniovertebral angle (CVA) to assess forward head posture. Sensorimotor control was assessed by the following measures: smooth pursuit neck torsion test (SPNT), overall stability index (OSI), and left and right rotation repositioning accuracy. A measure of autonomic nervous system function included the amplitude and latency of skin sympathetic response (SSR). Differences in variable measures were examined using the Student's t-test to compare the means of continuous variables between the two groups. One-way ANOVA was used to compare mean values in the three groups: postural kyphosis, Scheuermann's kyphosis, and normal kyphosis group. Pearson correlation was used to evaluate the relationship between participant's thoracic kyphosis magnitude (in each group separately and as an entire population) and their CVA, SPNT, OSI, head repositioning accuracy, and SSR latency and amplitude. Hyper-kyphosis participants had a significantly greater neck disability index compared to the normal kyphosis group (p < 0.001) with the SK group having greatest disability (p < 0.001). Statistically significant differences between the two kyphosis groups and the normal kyphosis group for all the sensorimotor measured variables were identified with the SK group having the most decreased efficiency of the measures in the hyper-kyphosis group, including: SPNT, OSI, and left and right rotation repositioning accuracy. In addition, there was a significant difference in neurophysiological findings for SSR amplitude (entire sample of kyphosis vs. normal kyphosis, p < 0.001), but there was no significant difference for SSR latency (p = 0.07). The CVA was significantly greater in the hyper-kyphosis group (p < 0.001). The magnitude of the thoracic kyphosis correlated with worsening CVA (with the SK group having the smallest CVA; p < 0.001) and the magnitude of the decreased efficiency of the sensorimotor control measures and the amplitude and latency of the SSR. The PK group, overall, showed the greatest correlations between thoracic kyphosis and measured variables. Participants with hyper-thoracic kyphosis exhibited abnormal sensorimotor control and autonomic nervous system dysfunction compared to those with normal thoracic kyphosis.

8.
BMC Public Health ; 23(1): 1045, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37264348

RESUMO

BACKGROUND: Most young adults and adolescents in the United Arab Emirates (UAE) do not meet the established internationally recommended physical activity levels per day. The Arab Teen Lifestyle Study (ATLS) physical activity questionnaire has been recommended for measuring self-reported physical activity of Arab adolescents and young adults (aged 14 years to mid-twenties). The first version of the ATLS has been validated with accelerometers and pedometers (r ≤ 0.30). The revised version of the questionnaire (ATLS-2, 2021) needs further validation. The aim of this study was to validate the self-reported subjective sedentary and physical activity time of the ATLS-2 (revised version) physical activity questionnaire with that of Fibion accelerometer-measured data. METHODS: In this cross-sectional study, 131 healthy adolescents and young adults (aged 20.47 ± 2.16 [mean ± SD] years (range 14-25 years), body mass index 23.09 ± 4.45 (kg/m2) completed the ATLS-2 and wore the Fibion accelerometer for a maximum of 7 days. Participants (n = 131; 81% non-UAE Arabs (n = 106), 13% Asians (n = 17) and 6% Emiratis (n = 8)) with valid ATLS-2 data without missing scores and Fibion data of minimum 10 h/day for at least 3 weekdays and 1 weekend day were analyzed. Concurrent validity between the two methods was assessed by the Spearman rho correlation and Bland-Altman plots. RESULTS: The questionnaire underestimated sedentary and physical activity time compared to the accelerometer data. Only negligible to weak correlations (r ≤ 0.12; p > 0.05) were found for sitting, walking, cycling, moderate intensity activity, high intensity activity and total activity time. In addition, a proportional/systematic bias was evident in the plots for all but two (walking and moderate intensity activity time) of the outcome measures of interest. CONCLUSIONS: Overall, self-reported ATLS-2 sedentary and physical activity time had low correlation and agreement with objective Fibion accelerometer measurements in adolescents and young adults in the UAE. Therefore, sedentary and physical activity assessment for these groups should not be limited to self-reported measures.


Assuntos
Árabes , Comportamento Sedentário , Humanos , Adolescente , Adulto Jovem , Autorrelato , Emirados Árabes Unidos , Estudos Transversais , Acelerometria/métodos , Exercício Físico , Inquéritos e Questionários , Estilo de Vida , Reprodutibilidade dos Testes
9.
J Clin Med ; 12(9)2023 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-37176657

RESUMO

The current investigation used somatosensory evoked potentials (SEPs) to assess differences in sensorimotor integration and somatosensory processing variables between asymptomatic individuals with and without forward head posture (FHP). We assessed different neural regions of the somatosensory pathway, including the amplitudes of the peripheral N9, spinal N13, brainstem P14, peak-to-peak amplitudes of parietal N20 and P27, and frontal N30 potentials. Central conduction time (N13-N20) was measured as the difference in peak latencies of N13 and N20. We measured these variables in 60 participants with FHP defined as a craniovertebral angle (CVA) < 50° and 60 control participants matched for age, gender, and body mass index (BMI) with normal FHP defined as CVA > 55°. Differences in variable measures were examined using the parametric t-test. Pearson's correlation was used to evaluate the relationship between the CVA and sensorimotor integration and SEP measurements. A generalized linear model (GLM) was used to compare the SEP measures between groups, with adjustment for educational level, marital status, BMI, and working hours per week. There were statistically significant differences between the FHP group and control group for all sensorimotor integration and SEP processing variables, including the amplitudes of spinal N13 (p < 0.005), brainstem P14 (p < 0.005), peak-to-peak amplitudes of parietal N20 and P27 (p < 0.005), frontal N30 potentials (p < 0.005), and the conduction time N13-N20 (p = 0.004). The CVA significantly correlated with all measured neurophysiological variables indicating that as FHP increased, sensorimotor integration and SEP processing became less efficient. FHP group correlations were: N9 (r = -0.44, p < 0.001); N13 (r = -0.67, p < 0.001); P14 (r = -0.58, p < 0.001); N20 (r = -0.49, p = 0.001); P27 (r = -0.58, p < 0.001); N30 potentials (r = -0.64, p < 0.001); and N13-N20 (r = -0.61, p < 0.001). GLM identified that increased working hours adversely affected the SEP measures (p < 0.005), while each 1° increase in the CVA was associated with improved SEP amplitudes and more efficient central conduction time (N13-N20; p < 0.005). Less efficient sensorimotor integration and SEP processing may be related to previous scientific reports of altered sensorimotor control and athletic skill measures in populations with FHP. Future investigations should seek to replicate our findings in different spine disorders and symptomatic populations in an effort to understand how improving forward head posture might benefit functional outcomes of patient care.

10.
J Clin Med ; 12(5)2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36902575

RESUMO

The current study aimed to determine whether participants with and without forward head posture (FHP) would respond differently in cervical nerve root function to various sitting positions. We measured peak-to-peak dermatomal somatosensory-evoked potentials (DSSEPs) in 30 participants with FHP and in 30 participants matched for age, sex, and body mass index (BMI) with normal head posture (NHP), defined as having a craniovertebral angle (CVA) >55°. Additional inclusion criteria for recruitment were individuals between the ages of 18 and 28 who were in good health and had no musculoskeletal pain. All 60 participants underwent C6, C7, and C8 DSSEPs evaluation. The measurements were taken in three positions: erect sitting, slouched sitting, and supine. We identified statistically significant differences in the cervical nerve root function in all postures between the NHP and FHP groups (p < 0.001), indicating that the FHP and NHP reacted differently in different positions. No significant differences between groups for the DSSEPs were identified for the supine position (p > 0.05), in contrast to the erect and slouched sitting positions, which showed a significant difference in nerve root function between the NHP and FHP (p < 0.001). The NHP group results were consistent with the prior literature and had the greatest DSSEP peaks when in the upright position. However, the participants in the FHP group demonstrated the largest peak-to-peak amplitude of DSSEPs while in the slouched position as opposed to an erect position. The optimal sitting posture for cervical nerve root function may be dependent upon the underlying CVA of a person, however, further research is needed to corroborate these findings.

11.
J Clin Med ; 12(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36675471

RESUMO

Forward head posture (FHP) is a common postural displacement that is significantly associated with neck pain, with higher risks of having neck pain in female and older populations. This study investigated the effect of two different forward head posture (FHP) interventions in elderly participants with poor posture and non-specific neck pain. Sixty-six elderly participants with a craniovertebral angle (CVA) < 50° were randomized into either a Chiropractic Biophyics® (CBP®) or a standardized exercise based FHP correction group (Standard Group). Both groups were treated for 18 sessions over a 6-week period. A 3-month post-treatment follow-up was also assessed with no further interventions. The CBP group received a mirror image® exercise and a Denneroll™ cervical traction orthotic (DCTO); the standard group performed a protocol of commonly used stretching and strengthening exercises for the neck. Both groups received 30 min of their respective interventions per session. The primary outcome was the CVA, with secondary outcomes including pain intensity, Berg balance score (BBS), head repositioning accuracy (HRA), and cervical range of motion (CROM). After 18 sessions (6 weeks later), the CBP group had statistically significant improvement in the CVA (p < 0.001), whereas the standard group did not. In contrast, both groups showed improved functional measurements on the BBS and HRA as well as improved pain intensity. However, at the 3-month follow-up (with no further treatment), there were statistically significant differences favoring the CBP group for all outcomes (p < 0.001). The differences in the between group outcomes at the 3-month follow-up indicated that the improved outcomes were maintained in the CBP group, while the standard group experienced regression of the initially improved outcomes at 6 weeks. It is suggested that the improvement in the postural CVA (in the CBP group but not in the standard group) is the driver of superior and maintained pain and functional outcomes.

12.
Nucleic Acids Res ; 51(1): 315-336, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36546762

RESUMO

Some of the most efficacious antiviral therapeutics are ribonucleos(t)ide analogs. The presence of a 3'-to-5' proofreading exoribonuclease (ExoN) in coronaviruses diminishes the potency of many ribonucleotide analogs. The ability to interfere with ExoN activity will create new possibilities for control of SARS-CoV-2 infection. ExoN is formed by a 1:1 complex of nsp14 and nsp10 proteins. We have purified and characterized ExoN using a robust, quantitative system that reveals determinants of specificity and efficiency of hydrolysis. Double-stranded RNA is preferred over single-stranded RNA. Nucleotide excision is distributive, with only one or two nucleotides hydrolyzed in a single binding event. The composition of the terminal basepair modulates excision. A stalled SARS-CoV-2 replicase in complex with either correctly or incorrectly terminated products prevents excision, suggesting that a mispaired end is insufficient to displace the replicase. Finally, we have discovered several modifications to the 3'-RNA terminus that interfere with or block ExoN-catalyzed excision. While a 3'-OH facilitates hydrolysis of a nucleotide with a normal ribose configuration, this substituent is not required for a nucleotide with a planar ribose configuration such as that present in the antiviral nucleotide produced by viperin. Design of ExoN-resistant, antiviral ribonucleotides should be feasible.


Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , Ribonucleotídeos , Humanos , Antivirais/farmacologia , Exorribonucleases/metabolismo , Ribonucleotídeos/química , RNA Viral/genética , RNA Viral/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/genética , Desenho de Fármacos
13.
J Clin Med ; 11(23)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36498603

RESUMO

The aim of this study was to investigate the feasibility and effect of a multimodal program for the management of chronic nonspecific neck pain CNSNP with the addition of a 3D adjustable posture corrective orthotic (PCO), with a focus on patient recruitment and retention. This report describes a prospective, randomized controlled pilot study with twenty-four participants with CNSNP and definite 3D postural deviations who were randomly assigned to control and study groups. Both groups received the same multimodal program; additionally, the study group received a 3D PCO to perform mirror image® therapy for 20−30 min while the patient was walking on a treadmill 2−3 times per week for 10 weeks. Primary outcomes included feasibility, recruitment, adherence, safety, and sample size calculation. Secondary outcomes included neck pain intensity by numeric pain rating scale (NPRS), neck disability index (NDI), active cervical ROM, and 3D posture parameters of the head in relation to the thoracic region. Measures were assessed at baseline and after 10 weeks of intervention. Overall, 54 participants were screened for eligibility, and 24 (100%) were enrolled for study participation. Three participants (12.5%) were lost to reassessment before finishing 10 weeks of treatment. The between-group mean differences in change scores indicated greater improvements in the study group receiving the new PCO intervention. Using an effect size of 0.797, α > 0.05, ß = 80% between-group improvements for NDI identified that 42 participants were required for a full-scale RCT. This pilot study demonstrated the feasibility of recruitment, compliance, and safety for the treatment of CNSNP using a 3D PCO to a multimodal program to positively affect CNSNP management.

14.
J Clin Med ; 11(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36362743

RESUMO

Sagittal cervical alignment is a clinically related feature in patients suffering from chronic cervical spondylotic radiculopathy (CSR). We designed this randomized trial to explore the effects of cervical lordosis (CL) correction in thirty chronic lower CSR patients with CL < 20°. Patients were assigned randomly into two equal groups, study (SG) and control (CG). Both groups received neck stretching and exercises and infrared radiation; additionally, the SG received cervical extension traction. Treatments were applied 3× per week for 10 weeks after which groups were followed for 3 months and 2 years. The amplitude of dermatomal somatosensory evoked potentials (DSSEPS), CL C2−C7, and pain scales (NRS) were measured. The SG had an increase in CL post-treatment (p < 0.0001), this was maintained at 3 months and 2 years. No statistical improvement in CL was found for the CG. A significant reduction in NRS for SG after 10 weeks of treatment with non-significant loss of change at 3 months and continued improvement at 2 years was found. CG had less significant improvement in post-treatment NRS; the 3-month and 2-year measures revealed significant worsening in NRS. An inverse linear correlation between increased CL and NRS was found (r = −0.49; p = 0.005) for both groups initially and maintained in SG at the final 2-year follow-up (r = −0.6; p = 0.01). At 10 weeks, we found significant improvements in DSSEPS for both groups (p < 0.0001). We identified a linear correlation between initial DSSEPs and CL for both groups (p < 0.0001), maintained only in the SG at the final follow-up for all levels (p < 0.0001). Improved CL in the SG correlated with significant improvements in nerve root function and pain rating in patients with CSR at short and long-term follow-up. These observed effects indicate that clinicians involved in the treatment of patients with symptoms of cervical degenerative disorders should add sagittal curve correction to their armamentarium of rehabilitation procedures for relevant patient populations.

15.
Eur Spine J ; 31(12): 3452-3461, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36227366

RESUMO

PURPOSE: The current investigation aimed to compare the sensorimotor integration, sensorimotor control, and cost of cognitive-motor dual task during walking, in persons with chronic WAD as compared to matched chronic idiopathic neck pain and normal healthy controls. METHODS: A cross-sectional, case control design comparing 30 participants in each of two study groups (chronic WAD and chronic idiopathic neck pain) to a matched control group was conducted. Measurements included: (1) the cranio-vertebral angle (CVA), (2) left and right rotation head repositioning accuracy (HRA), (3) frontal N30 amplitudes to assess sensorimotor integration, (4) dual cognitive gait cost (DCGC). RESULTS: A statistically significant difference for the CVA was found between groups: WAD 36.8° ± 3.4, chronic pain 44.5° ± 1.5, and controls 47.1° ± 4; p < 0.05. MANOVA revealed significant group differences for the N30 amplitude (p < 0.05), where the WAD group had the greatest amplitude. Statistically significant differences among the three groups were found for HRA left and right where the WAD group had the greatest error, (p < 0.05). Post hoc tests revealed that the WAD group had the highest dual-task cost during walking, (p < 0.05). Significant linear correlations between the CVA and N30 amplitude, HRA, and DCGC were identified in all 3 groups, (p < 0.05). CONCLUSIONS: Compared to both a matched control group and chronic neck pain group, whiplash-injured persons have greater forward head posture, greater error in sensorimotor control, and an altered ability to perform a motor task with a simultaneous cognitive task.


Assuntos
Dor Crônica , Traumatismos em Chicotada , Humanos , Cervicalgia/complicações , Dor Crônica/complicações , Estudos Transversais , Traumatismos em Chicotada/complicações , Doença Crônica , Cognição
16.
bioRxiv ; 2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-35982684

RESUMO

Some of the most efficacious antiviral therapeutics are ribonucleos(t)ide analogs. The presence of a 3'-to-5' proofreading exoribonuclease (ExoN) in coronaviruses diminishes the potency of many ribonucleotide analogs. The ability to interfere with ExoN activity will create new possibilities for control of SARS-CoV-2 infection. ExoN is formed by a 1:1 complex of nsp14 and nsp10 proteins. We have purified and characterized ExoN using a robust, quantitative system that reveals determinants of specificity and efficiency of hydrolysis. Double-stranded RNA is preferred over single-stranded RNA. Nucleotide excision is distributive, with only one or two nucleotides hydrolyzed in a single binding event. The composition of the terminal basepair modulates excision. A stalled SARS-CoV-2 replicase in complex with either correctly or incorrectly terminated products prevents excision, suggesting that a mispaired end is insufficient to displace the replicase. Finally, we have discovered several modifications to the 3'-RNA terminus that interfere with or block ExoN-catalyzed excision. While a 3'-OH facilitates hydrolysis of a nucleotide with a normal ribose configuration, this substituent is not required for a nucleotide with a planar ribose configuration such as that present in the antiviral nucleotide produced by viperin. Design of ExoN-resistant, antiviral ribonucleotides should be feasible.

17.
Hong Kong Physiother J ; 42(1): 41-53, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35782695

RESUMO

Background: Although different types of neural mobilization (NM) exercises induce different amounts of longitudinal nerve excursion and strain, the question whether the increased longitudinal stress and nerve excursion from sliding or tensioning intervention may subtly affect the neural functions has not been answered yet. Objective: To compare the effects of tensioning NM versus sliding NM of the median nerve on peripheral and autonomic nervous system function. Methods: In this randomized controlled trial, 90 participants were randomly assigned to tensioning NM, sliding NM, or sham NM. The neurophysiological outcome measures included peak-to-peak amplitude of the dermatomal somatosensory evoked potential (DSSEP) for dermatomes C6, C7, C8, and T1. Secondary outcome measures included amplitude and latency of skin sympathetic response. All outcome measures were assessed pretreatment, immediately after the two weeks of treatment and one week after the last session of the treatment. Results: A 2-way repeated measures ANOVA revealed significant differences between the three groups. The post hoc analysis indicated that tensioning NM significantly decreased the dermatomal amplitude for C6, C7, C8, and T1 ( p < 0 . 005 ). Sympathetic skin responses in the gliding NM group showed lower amplitudes and prolonged latencies post-treatment when compared to tensioning NM group ( p < 0 . 05 ). In contrast, no significant changes were observed in the DSSEPs and skin sympathetic responses for participants in the sham treatment group ( p > 0 . 05 ). Conclusions: A tensioning NM on the median nerve had a possible adverse effect on the neurophysiology variables of the nerves involved in the neural mobilization. Thus, tensioning NM with the current parameters that place increased stress and strain on the peripheral nervous system should be avoided.

18.
J Clin Med ; 12(1)2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36615020

RESUMO

Fibromyalgia syndrome (FMS) is a common condition lacking strong diagnostic criteria; these criteria continue to evolve as more and more studies are performed to explore it. This investigation sought to identify whether participants with FMS have more frequent and larger postural/spinal displacements in comparison to a matched control group without the condition of FMS. A total of 67 adults (55 females) out of 380 participants with FMS were recruited. Participants with FMS were sex- and age-matched with 67 asymptomatic participants (controls) without FMS. We used a three-dimensional (3D) postural assessment device (Formetric system) to analyze five posture variables in each participant in both groups: (1) thoracic kyphotic angle, (2) trunk imbalance, (3) trunk inclination, (4) lumbar lordotic angle, and (5) vertebral rotation. In order to determine whether 3D postural measures could predict the likelihood of a participant having FMS, we applied the matched-pairs binary logistic regression analysis. The 3D posture measures identified statistically and clinically significant differences between the FMS and control groups for each of the five posture variables measured (p < 0.001). For three out of five posture measurements assessed, the binary logistic regression identified there was an increased probability of having FMS with an increased: (1) thoracic kyphotic angle proportional odds ratio [Prop OR] = 1.76 (95% CI = 1.03, 3.02); (2) sagittal imbalance Prop OR = 1.54 (95% CI = 0.973, 2.459); and (3) surface rotation Prop OR = 7.9 (95% CI = 1.494, 41.97). We identified no significant probability of having FMS for the following two postural measurements: (1) coronal balance (p = 0.50) and (2) lumbar lordotic angle (p = 0.10). Our study's findings suggest there is a strong relationship between 3D spinal misalignment and the diagnosis of FMS. In fact, our results support that thoracic kyphotic angle, sagittal imbalance, and surface rotation are predictors of having FMS.

19.
PLoS One ; 16(11): e0258752, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34748549

RESUMO

BACKGROUND: Fatigue is considered one of the most common symptoms of multiple sclerosis (MS) and lacks a current standardized treatment. Therefore, the aim of this study was to examine the feasibility and effectiveness of a cognition-targeted exercise versus symptom-targeted exercise for MS fatigue. METHODS: In this Pilot, parallel-group, randomized controlled trial, sixty participants with multiple sclerosis, were randomly assigned to either a Cognition-Targeted Exercise (CTE) (N = 30, mean age 41) or a Symptom-Targeted Exercise (STE) (N = 30, mean age 42). The participants in the experimental group received eight, 50-minute sessions of weekly Cognitive Behavior Therapy (CBT) in addition to a CTE Program; whereas, participants in the control group received eight, 50-minute sessions of weekly CBT in addition to the standardized physiotherapy program (STE Program). Feasibility was assessed through recruitment rate, participant retention, adherence and safety, in addition to clinical outcome measures, including: (1) Modified Fatigue Impact Scale (MFIS), (2) Work and Social Adjustment Scale (WSAS), (3) Hospital Anxiety and Depression Scale (HADS), and Perceived Stress Scale (PSS). All outcome measures were assessed at baseline (pretreatment), following completion of the eight visit intervention protocol, and at 3-months follow-up. RESULTS: The recruitment rate was 60% and 93% of participants completed the entire study. The recruited participants complied with 98% of the required visits. No adverse events were recorded. A Generalized Estimation Equation Model revealed a significant difference over time as an interaction term during the post and follow up visit for all clinical outcome measures (p < .001). CONCLUSION: The addition of CTE to CBT exhibited positive and more lasting influence on MS fatigue outcomes compared to Symptom-Targeted Exercise (STE). Feasibility and efficacy data from this pilot study provide support for a full-scale RCT of CTE as an integral component of Multiple Sclerosis fatigue management.


Assuntos
Terapia Cognitivo-Comportamental , Terapia por Exercício , Fadiga/terapia , Esclerose Múltipla/terapia , Adulto , Idoso , Cognição/fisiologia , Exercício Físico , Fadiga/complicações , Fadiga/fisiopatologia , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/fisiopatologia , Avaliação de Resultados em Cuidados de Saúde/normas , Projetos Piloto , Qualidade de Vida
20.
Mol Cell ; 81(21): 4467-4480.e7, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34687604

RESUMO

Viral RNA-dependent RNA polymerases (RdRps) are a target for broad-spectrum antiviral therapeutic agents. Recently, we demonstrated that incorporation of the T-1106 triphosphate, a pyrazine-carboxamide ribonucleotide, into nascent RNA increases pausing and backtracking by the poliovirus RdRp. Here, by monitoring enterovirus A-71 RdRp dynamics during RNA synthesis using magnetic tweezers, we identify the "backtracked" state as an intermediate used by the RdRp for copy-back RNA synthesis and homologous recombination. Cell-based assays and RNA sequencing (RNA-seq) experiments further demonstrate that the pyrazine-carboxamide ribonucleotide stimulates these processes during infection. These results suggest that pyrazine-carboxamide ribonucleotides do not induce lethal mutagenesis or chain termination but function by promoting template switching and formation of defective viral genomes. We conclude that RdRp-catalyzed intra- and intermolecular template switching can be induced by pyrazine-carboxamide ribonucleotides, defining an additional mechanistic class of antiviral ribonucleotides with potential for broad-spectrum activity.


Assuntos
Pirazinas/química , Vírus de RNA/genética , RNA Viral/genética , RNA Polimerase Dependente de RNA/genética , Recombinação Genética , Ribonucleotídeos/química , Animais , Antivirais , Catálise , Células Cultivadas , Técnicas Genéticas , Genoma , Genoma Viral , Recombinação Homóloga , Humanos , Cinética , Camundongos , Camundongos Transgênicos , Simulação de Dinâmica Molecular , Mutagênese , Nucleotídeos/genética , Conformação Proteica , RNA/química , RNA Polimerase Dependente de RNA/metabolismo , RNA-Seq , Transgenes , Virulência
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