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1.
Radiol Case Rep ; 19(11): 5513-5518, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39285982

RESUMO

Secondary Sjogren's syndrome (sSS) is a medical condition that occurs in individuals with autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. It predominantly affects females rather than males. We present a case of a 32-year-old female with a 3-year history of rheumatoid arthritis (RA) who presented to the internal medicine and rheumatology clinic with several complaints, including swelling and tenderness in her left jaw, dry mouth (xerostomia), irritated eyes (xerophthalmia), severe joint pain, and a decreased in saliva production. The blood tests demonstrate the presence of anti-SSA and anti-SSB autoantibodies and elevation of total leukocyte count (TLC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels, indicating inflammation. A high-frequency ultrasound confirmed the diagnosis of Secondary Sjogren's syndrome grade II, specifically affecting the left parotid gland (PG).

2.
Langenbecks Arch Surg ; 409(1): 270, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39235593

RESUMO

PURPOSE: Choosing the best stump closure method for laparoscopic appendectomy has been a debated issue, especially for patients with acute appendicitis. The lack of consensus in the literature and the diverse techniques available have prompted the need for a comprehensive evaluation to guide surgeons in selecting the most optimal appendiceal stump closure method. METHODS: A comprehensive search was conducted on multiple databases from inception until December 2023 to find relevant studies according to eligibility criteria. The primary outcome was the incidence of total complications. RESULTS: 25 studies with a total of 3308 patients were included in this study, overall complications did not reveal a significant advantage for any intervention (RR = 0.72, 95% CI: 0.53; 1.01), Superficial and deep infection risks were similar across all methods, Operative time was significantly longer with endoloop and Intracorporeal sutures (MD = 7.07, 95% CI: 3.28; 10.85) (MD = 26.1, 95% CI: 20.9; 31.29). CONCLUSIONS: There are no significant differences in overall complications among closure methods. However, Intracorporeal sutures and endoloop techniques were associated with extended operative durations.


Assuntos
Apendicectomia , Apendicite , Laparoscopia , Apendicectomia/métodos , Apendicectomia/efeitos adversos , Humanos , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Apendicite/cirurgia , Técnicas de Sutura , Metanálise em Rede , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Duração da Cirurgia , Resultado do Tratamento
3.
Bioorg Chem ; 152: 107759, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39213797

RESUMO

In the present study, the design and synthesis of novel coumarin derivatives 8a-h, 11a-d and 16a-c as potential selective inhibitors for the tumor associated human carbonic anhydrase isoforms (hCA IX and XII) was reported. All the newly synthesized derivatives showed potent to mild activity against the targeted CA IX (KI = 0.08-9.57 µM), with selectivity indices over CA I (SI = 2.0-21.9) and over CA II (SI = 1.1-15.7). They showed similar activities against CA XII (KI = 0.06-9.48 µM) with selectivity indices over CA I (SI = 1.4-21.2) and CA II (SI = 0.9-15.5). Compound 16b featuring sulfonamide function possessed promising inhibitory activities against the targeted isoforms CA IX and XII with KI values of 0.08 and 0.06 µM, respectively. Interestingly, it was found that using compound 16b at a nontoxic concentration as an adjuvant with Doxorubicin against MCF-7 cells enhanced the cytotoxicity under hypoxia by almost 3.5 folds; IC50 decreased from 25.74 to 7.43 µM. Therefore, compound 16b restored the cytotoxicity of Doxorubicin against MCF-7 cells under hypoxia, almost as normoxia. Furthermore, flow cytometry analysis of a combination treatment of compound 16b and Doxorubicin to the MCF7 cell line revealed an increase in cell cycle arrest at the G2/M phase and a more efficient apoptotic effect than Doxorubicin alone. Furthermore, compound 16b showed no cytotoxicity against normal breast MCF-10A cell line (IC50 = 296.25 µM).


Assuntos
Anidrase Carbônica IX , Inibidores da Anidrase Carbônica , Anidrases Carbônicas , Proliferação de Células , Cumarínicos , Relação Dose-Resposta a Droga , Doxorrubicina , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Inibidores da Anidrase Carbônica/farmacologia , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/síntese química , Cumarínicos/farmacologia , Cumarínicos/química , Cumarínicos/síntese química , Anidrase Carbônica IX/antagonistas & inibidores , Anidrase Carbônica IX/metabolismo , Doxorrubicina/farmacologia , Células MCF-7 , Anidrases Carbônicas/metabolismo , Relação Estrutura-Atividade , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Antígenos de Neoplasias/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos
4.
J Cereb Blood Flow Metab ; : 271678X241270528, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39113421

RESUMO

Neurological symptoms are central to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), yet its underlying neurophysiological mechanisms remain elusive. We examined a neglected aspect of task-based functional MRI, focusing on how blood oxygenation level-dependent (BOLD) signals alter during cognitive tasks in ME/CFS. This prospective observational study utilised MRI scans on ME/CFS participants and healthy controls (HCs) with sedentary lifestyles (ACTRN12622001095752). Participants completed two blocks of a Symbol Digit Modalities Test, with 30 trials per block split into two sets. The fMRI signal changes between blocks and sets were compared within and between groups. Thirty-four ME/CFS participants (38 years ± 10; 27 women) and 34 HCs (38 ± 10; 27 women), were evaluated. In the second task block, ME/CFS participants exhibited increased activation in the right postcentral gyrus, contrasting with decreased activation in multiple regions in HCs. These results were further confirmed by significantly higher bilateral dynamic changes (2nd vs 1st set) in the motor, sensory and cognitive cortex in ME/CFS compared to HCs and significant correlations between those changes in the left primary motor cortex with fatigue severities. BOLD adaptation, potentially improving energy economy, was absent in ME/CFS, which may provide an underlying neurophysiological process in ME/CFS.

5.
Perioper Med (Lond) ; 13(1): 87, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39123238

RESUMO

BACKGROUND: Emergency cholecystectomy is the mainstay in treating acute cholecystitis (AC). In actual practice, perioperative prophylactic antibiotics are used to prevent postoperative infectious complications (PIC), but their effectiveness lacks evidence. We aim to investigate the efficacy of prophylactic antibiotics in emergency cholecystectomy. METHODS: We searched PubMed, Embase, Cochrane CENTRAL, Web of Science (WOS), and Scopus up to June 14, 2023. We included randomized controlled trials (RCTs) that involved patients diagnosed with mild to moderate AC according to Tokyo guidelines who were undergoing emergency cholecystectomy and were administered preoperative and/or postoperative antibiotics as an intervention group and compared to a placebo group. For dichotomous data, we applied the risk ratio (RR) and the 95% confidence interval (CI), while for continuous data, we used the mean difference (MD) and 95% CI. RESULTS: We included seven RCTs encompassing a collective sample size of 1747 patients. Our analysis showed no significant differences regarding total PIC (RR = 0.84 with 95% CI (0.63, 1.12), P = 0.23), surgical site infection (RR = 0.79 with 95% CI (0.56, 1.12), P = 0.19), distant infections (RR = 1.01 with 95% CI (0.55, 1.88), P = 0.97), non-infectious complications (RR = 0.84 with 95% CI (0.64, 1.11), P = 0.22), mortality (RR = 0.34 with 95% CI (0.04, 3.23), P = 0.35), and readmission (RR = 0.69 with 95% CI (0.43, 1.11), P = 0.13). CONCLUSION: Perioperative antibiotics in patients with mild to moderate acute cholecystitis did not show a significant reduction of postoperative infectious complications after emergency cholecystectomy. (PROSPERO registration number: CRD42023438755).

6.
World J Surg ; 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39072840

RESUMO

BACKGROUND: Despite the success of sleeve gastrectomy (SG) in of weight loss and treatment of the medical problems associated with obesity, some concerns have arisen about the need for revisional surgeries after SG in some patients. This study aimed to present an updated and comprehensive comparison among the presently available revisional surgeries employed explicitly in cases of inadequate outcomes after SG, which is the most frequently performed bariatric surgery in contemporary practice. METHODS: This network meta-analysis included studies that compared the outcomes of different revisional bariatric procedures after an inadequate outcome of SG. RESULTS: Searching across the electronic databases yielded 31 eligible articles. Re-SG was associated with the highest rate of significant complications. Patients treated with single anastomosis duodenal-ileal bypass (SADI) had a significantly higher percentage of total weight loss (%TWL) than those treated with one anastomosis gastric bypass (OAGB) and Roux-en-Y gastric bypass (RYGB). The percentage of excess weight loss (%EWL) at the end of the follow-up period was significantly higher in patients in the SADI group compared to those in the RYGB group and the OAGB, and re-SG exhibited the least values compared to SADI, biliopancreatic diversion with duodenal switch (BPD/DS), and OAGB. Significantly lower rates of reflux worsening/de novo development were observed in the SADI group compared to the OAGB group and the re-SG group, which showed significantly higher rates than SADI and RYGB. CONCLUSION: Our comprehensive network meta-analysis highlights SADI as a promising revisional option post-SG, demonstrating superior weight loss outcomes, lower significant complication rates, and a favorable impact on reflux compared to other procedures. While acknowledging the limitations of our study, these findings support the potential efficacy of SADI in addressing the challenges of inadequate weight loss after sleeve gastrectomy.

8.
J Ultrasound ; 27(3): 621-634, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38879835

RESUMO

PURPOSE: In correlation with magnetic resonance imaging (MRI), this study attempts to assess the effectiveness of the diagnostic of ultrasonography (US) features and shear wave elastography (SWE) in determining the different causes of heel pain. MATERIALS AND METHODS: 55 heels with a mean age of 38.33 ± 10.8 were included in the study (10 control cases and 41 cases, 4 of which had bilateral heel pain). There were 23 female cases (56.1%) and 18 male cases (43.95%). Examinations using shear wave elastography (SWE) and ultrasound (US) were done in different positions. MRI and the obtained data were correlated. RESULTS: When used to diagnose different heel pain causes, ultrasound demonstrated great sensitivity and specificity. SWE demonstrated a good correlation with MRI findings and enhanced the ultrasound's diagnostic precision in identifying plantar fasciitis early on (increased accuracy from 88.9 to 93.33% with 100% sensitivity and 83.3% specificity) and Achilles tendinopathy (increased accuracy from 88.9 to 97.8 with 94.7% sensitivity and 100% specificity). CONCLUSION: In summary, we concluded that heel pain can be efficiently examined by both ultrasound (US) and shear wave elastography (SWE) with the former being used as the primary effective tool and the latter being done to increase diagnostic accuracy. We also concluded that SWE improved the ultrasound's diagnostic precision in identifying patients with early plantar fasciitis and Achilles tendinopathy and showed a robust relationship with clinical outcomes, enhancing patient evaluation and follow-up.


Assuntos
Técnicas de Imagem por Elasticidade , Calcanhar , Sensibilidade e Especificidade , Ultrassonografia , Humanos , Técnicas de Imagem por Elasticidade/métodos , Masculino , Feminino , Calcanhar/diagnóstico por imagem , Adulto , Estudos Transversais , Diagnóstico Diferencial , Pessoa de Meia-Idade , Ultrassonografia/métodos , Fasciíte Plantar/diagnóstico por imagem , Dor/diagnóstico por imagem , Dor/etiologia , Imageamento por Ressonância Magnética , Tendinopatia/diagnóstico por imagem , Tendão do Calcâneo/diagnóstico por imagem
9.
Ann Neurol ; 96(2): 365-377, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38845484

RESUMO

OBJECTIVE: The long-term consequences of traumatic brain injury (TBI) on brain structure remain uncertain. Given evidence that a single significant brain injury event increases the risk of dementia, brain-age estimation could provide a novel and efficient indexing of the long-term consequences of TBI. Brain-age procedures use predictive modeling to calculate brain-age scores for an individual using structural magnetic resonance imaging (MRI) data. Complicated mild, moderate, and severe TBI (cmsTBI) is associated with a higher predicted age difference (PAD), but the progression of PAD over time remains unclear. We sought to examine whether PAD increases as a function of time since injury (TSI) and if injury severity and sex interacted to influence this progression. METHODS: Through the ENIGMA Adult Moderate and Severe (AMS)-TBI working group, we examine the largest TBI sample to date (n = 343), along with controls, for a total sample size of n = 540, to replicate and extend prior findings in the study of TBI brain age. Cross-sectional T1w-MRI data were aggregated across 7 cohorts, and brain age was established using a similar brain age algorithm to prior work in TBI. RESULTS: Findings show that PAD widens with longer TSI, and there was evidence for differences between sexes in PAD, with men showing more advanced brain age. We did not find strong evidence supporting a link between PAD and cognitive performance. INTERPRETATION: This work provides evidence that changes in brain structure after cmsTBI are dynamic, with an initial period of change, followed by relative stability in brain morphometry, eventually leading to further changes in the decades after a single cmsTBI. ANN NEUROL 2024;96:365-377.


Assuntos
Lesões Encefálicas Traumáticas , Imageamento por Ressonância Magnética , Humanos , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/complicações , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos de Coortes , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Idoso , Envelhecimento/patologia , Senilidade Prematura/diagnóstico por imagem , Senilidade Prematura/patologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-38772940

RESUMO

The underlying brain mechanisms of ketamine in treating chronic suicidality and the characteristics of patients who will benefit from ketamine treatment remain unclear. To address these gaps, we investigated temporal variations of brain functional synchronisation in patients with suicidality treated with ketamine in a 6-week open-label oral ketamine trial. The trial's primary endpoint was the Beck Scale for Suicide Ideation (BSS). Patients who experienced greater than 50% improvement in BSS scores or had a BSS score less than 6 at the post-treatment and follow-up (10 weeks) visits were considered responders and persistent responders, respectively. The reoccurring and transient connectivity pattern (termed brain state) from 29 patients (45.6 years ± 14.5, 15 females) were investigated by dynamic functional connectivity analysis of resting-state functional MRI at the baseline, post-treatment, and follow-up. Post-treatment patients showed significantly more (FDR-Q = 0.03) transitions among whole brain states than at baseline. We also observed increased dwelling time (FDR-Q = 0.04) and frequency (FDR-Q = 0.04) of highly synchronised brain state at follow-up, which were significantly correlated with BSS scores (both FDR-Q = 0.008). At baseline, persistent responders had higher fractions (FDR-Q = 0.03, Cohen's d = 1.39) of a cognitive control network state with high connectivities than non-responders. These findings suggested that ketamine enhanced brain changes among different synchronisation patterns and enabled high synchronisation patterns in the long term, providing a possible biological pathway for its suicide-prevention effects. Moreover, differences in cognitive control states at baseline may be used for precise ketamine treatment planning.

11.
World J Surg ; 48(6): 1467-1480, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38629863

RESUMO

BACKGROUND: In patients undergoing pancreaticoduodenectomy (PD), there has been some evidence favoring pancreaticogastrostomy (PG) over pancreatojejunostomy (PJ) in the occurrence of postoperative pancreatic fistulas (POPF) and considering PG as a safer anastomotic technique. However, other publications revealed comparable incidences of POPF attributed to both techniques. The current work attempts to reach a more consolidated conclusion about such an issue. METHODS: This is a systematic review and meta-analysis that analyzed the studies comparing PG and PJ during PD in terms of the rate of POPF occurrence. Studies were obtained by searching the Scopus, PubMed Central, and Cochrane Central Register of Controlled Trials databases. RESULTS: 35 articles published between 1995 and 2022 presented data from 14,666 patients; 4547 underwent PG and 10,119 underwent PJ. Statistically significant lower rates of POPF (p = 0.044) and clinically relevant CR-POPF (p = 0.043) were shown in the PG group. The post-pancreatectomy hemorrhage (PPH) was significantly higher in the PG group, while no significant difference was found between the two groups in the clinically significant PPH. No statistically significant differences were found regarding the amount of intraoperative blood loss, length of hospital stay, DGE, overall morbidity rates, reoperation rates, or mortality rates. The percentage of male sex in the PG group and the percentage of soft pancreas in the PJ group seem to influence the odds ratio of CR-POPF (p = 0.076 and 0.074, respectively). CONCLUSION: The present study emphasizes the superiority of PG over PJ regarding CR-POPF rates. Higher rates of postoperative hemorrhage were associated with PG. Yet, the clinically significant hemorrhage rate was comparable between the two groups.


Assuntos
Gastrostomia , Fístula Pancreática , Pancreaticoduodenectomia , Pancreaticojejunostomia , Complicações Pós-Operatórias , Humanos , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Pancreaticojejunostomia/métodos , Pancreaticojejunostomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Gastrostomia/métodos , Gastrostomia/efeitos adversos , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Incidência , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos
12.
Bioorg Chem ; 147: 107372, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38653152

RESUMO

Joining the global demand for the discovery of potent NSAIDs with minimized ulcerogenic effect, new pyrazole clubbed thiazole derivatives 5a-o were designed and synthesized. The new derivatives were initially evaluated for their analgesic activity. Eight compounds 5a, 5c, 5d, 5e, 5f, 5h, 5m, and 5o showed higher activity than Indomethacin (potency = 105-130 % vs. 100 %). Subsequently, they were picked for further evaluation of their anti-inflammatory activity, ulcerogenic liability as well as toxicological studies. Derivatives 5h and 5m showed a potential % edema inhibition after 3 h (79.39 % and 72.12 %, respectively), with a promising safety profile and low ulcer indices (3.80 and 3.20, respectively). The two compounds 5h and 5m were subjected to in vitro COX-1 and COX-2 inhibition assay. The candidate 5h showed nearly equipotent COX-1 inhibition (IC50 = 38.76 nM) compared to the non-selective reference drug Indomethacin (IC50 = 35.72 nM). Compound 5m expressed significant inhibitory activities and a higher COX-2 selectivity index (IC50 = 87.74 nM, SI = 2.05) in comparison with Indomethacin (SI = 0.52), with less selectivity than Celecoxib (SI = 8.31). Simulation docking studies were carried out to gain insights into the binding interaction of compounds 5h and 5m in the vicinity of COX-1 and COX-2 enzymes that illustrated the importance of pyrazole clubbed thiazole core in hydrogen bonding interactions. The thiazole motif of compounds 5h and 5m exhibited a well orientation toward COX-1 Arg120 key residue by hydrogen bonding interactions. Compound 5h revealed an additional arene-cation interaction with Arg120 that could rationalize its superior COX-1 inhibitory activity. Compounds 5h and 5m overlaid the co-crystallized ligand Celecoxib I differently in the active site of COX-2. Compound 5m showed an enhanced accommodation with binding energy of - 6.13 vs. - 1.70 kcal/mol of compounds 5h. The naphthalene ring of compound 5m adopted the Celecoxib I benzene sulfonamide region that is stabilized by hydrogen-arene interactions with the hydrophobic sidechains of the key residues Ser339 and Phe504. Further, the core structure of compound 5m, pyrazole clubbed thiazole, revealed deeper hydrophobic interactions with Ala513, Leu517 and Val509 residues. Finally, a sensitive and accurate UPLC-MS/MS method was developed for the simultaneous estimation of some selected promising pyrazole derivatives in rat plasma. Accordingly, compounds 5h and 5m were suggested to be promising potent analgesic and anti-inflammatory agents with improved safety profiles and a novel COX isozyme modulation activity.


Assuntos
Analgésicos , Anti-Inflamatórios não Esteroides , Ciclo-Oxigenase 2 , Edema , Simulação de Acoplamento Molecular , Tiazóis , Animais , Masculino , Camundongos , Ratos , Analgésicos/farmacologia , Analgésicos/química , Analgésicos/síntese química , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/síntese química , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/síntese química , Relação Dose-Resposta a Droga , Descoberta de Drogas , Edema/tratamento farmacológico , Edema/induzido quimicamente , Estrutura Molecular , Pirazóis/química , Pirazóis/farmacologia , Pirazóis/síntese química , Relação Estrutura-Atividade , Tiazóis/química , Tiazóis/farmacologia , Tiazóis/síntese química
13.
Heliyon ; 10(7): e27965, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38560161

RESUMO

Background: Following the World Health Organization declaration, COVID-19 was first appearance in Sudan was in March 2020. Cases were reported to the Sudan Federal Ministry of Heath through the surveillance system from different sources. This study used surveillance data from 2020 to 2021 to describe the epidemiologic patterns of COVID-19 occurrence in Sudan and provide insight for better preparedness and response. Methods: Through a retrospective descriptive study, COVID19 cases records obtained from the national surveillance line-list in Surveillance and Information Directorate in Federal Ministry of Health. The analysis of data was done with SPSS version 21. Descriptive analysis done by frequencies and percentages, and further analysis through performing multivariate logistic regression. Results: Out of 48,545 suspected cases tested for COVID-19 using RT-PCR, 27,453 (56.5%) tested positive with case fatality ratio of 6.5%. Higher death rate among elderly (78% > 60-year-old) and males (70.1%). From the reported cases, 53.8% showed no symptoms, while the common symptoms among symptomatic patients were; fever (26.4%), cough (19.1%), shortness of breath (16.8%) with small proportion (4.5%) reported loss of smell and taste. Specific states, Khartoum, Gezira and Red Sea showed highest prevalence. The disease peaked four times during 2020-2021, with a proposed alert threshold of 200-250 cases per week acting as an explosion point nationwide. Conclusions: The high case fatality rate in the country requires further analysis, as well as the high proportion of asymptomatic infection. This will be ensured by improving the quality and completeness of surveillance data. A proposed threshold of 200-250 cases per week should be an alert to augment the measures of controlling the pandemic over the country, including providing enough supplies to decrease mortality.

14.
J Magn Reson Imaging ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38339792

RESUMO

BACKGROUND: The brainstem is a crucial component of the central autonomic nervous (CAN) system. Functional MRI (fMRI) of the brainstem remains challenging due to a range of factors, including diverse imaging protocols, analysis, and interpretation. PURPOSE: To develop an fMRI protocol for establishing a functional atlas in the brainstem. STUDY TYPE: Prospective cross-sectional study. SUBJECTS: Ten healthy subjects (four males, six females). FIELD STRENGTH/SEQUENCE: Using a 3.0 Tesla MR scanner, we acquired T1-weighted images and three different fMRI scans using fMRI protocols of the optimized functional Imaging of Brainstem (FIBS), the Human Connectome Project (HCP), and the Adolescent Brain Cognitive Development (ABCD) project. ASSESSMENT: The temporal signal-to-noise-ratio (TSNR) of fMRI data was compared between the FIBS, HCP, and ABCD protocols. Additionally, the main normalization algorithms (i.e., FSL-FNIRT, SPM-DARTEL, and ANTS-SyN) were compared to identify the best approach to normalize brainstem data using root-mean-square (RMS) error computed based on manually defined reference points. Finally, a functional autonomic brainstem atlas that maps brainstem regions involved in the CAN system was defined using meta-analysis and data-driven approaches. STATISTICAL TESTS: ANOVA was used to compare the performance of different imaging and preprocessing pipelines with multiple comparison corrections (P ≤ 0.05). Dice coefficient estimated ROI overlap, with 50% overlap between ROIs identified in each approach considered significant. RESULTS: The optimized FIBS protocol showed significantly higher brainstem TSNR than the HCP and ABCD protocols (P ≤ 0.05). Furthermore, FSL-FNIRT RMS error (2.1 ± 1.22 mm; P ≤ 0.001) exceeded SPM (1.5 ± 0.75 mm; P ≤ 0.01) and ANTs (1.1 ± 0.54 mm). Finally, a set of 12 final brainstem ROIs with dice coefficient ≥0.50, as a step toward the development of a functional brainstem atlas. DATA CONCLUSION: The FIBS protocol yielded more robust brainstem CAN results and outperformed both the HCP and ABCD protocols. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

15.
J Youth Adolesc ; 53(5): 1029-1046, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38217837

RESUMO

Wellbeing is protective against the emergence of psychopathology. Neurobiological markers associated with mental wellbeing during adolescence are important to understand. Limited research has examined neural networks (white matter tracts) and mental wellbeing in early adolescence specifically. A cross-sectional diffusion tensor imaging analysis approach was conducted, from the Longitudinal Adolescent Brain study, First Hundred Brains cohort (N = 99; 46.5% female; Mage = 13.01, SD = 0.55). Participants completed self-report measures including wellbeing, quality-of-life, and psychological distress. Potential neurobiological profiles using fractional anisotropy, axial, and radial diffusivity were determined via a whole brain voxel-wise approach, and hierarchical cluster analysis of fractional anisotropy values, obtained from 21 major white matter tracts. Three cluster groups with significantly different neurobiological profiles were distinguished. No significant differences were found between the three cluster groups and measures of wellbeing, but two left lateralized significant associations between white matter tracts and wellbeing measures were found. These results provide preliminary evidence for potential neurobiological markers of mental health and wellbeing in early adolescence and should be tracked longitudinally to provide more detailed and robust findings.


Assuntos
Substância Branca , Humanos , Adolescente , Feminino , Masculino , Substância Branca/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Estudos Transversais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imagem de Difusão por Ressonância Magnética
16.
J Psychiatr Res ; 169: 192-200, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38042058

RESUMO

Ongoing stress results in hippocampal neuro-structural alterations which produce pathological consequences, including depression and suicidality. Ketamine may ameliorate stress related illnesses, including suicidality, via neuroplasticity processes. This novel study sought to determine whether oral ketamine treatment specifically affects hippocampal (whole and subfield) volumes in patients with chronic suicidality and MDD. It was hypothesised that oral ketamine treatment would differentially alter hippocampal volumes in trial participants categorised as ketamine responders, versus those who were non-responders. Twenty-eight participants received 6 single, weekly doses of oral ketamine (0.5-3 mg/kg) and underwent MRI scans at pre-ketamine (week 0), post-ketamine (week 6), and follow up (week 10). Hippocampal subfield volumes were extracted using the longitudinal pipeline in FreeSurfer. Participants were grouped according to ketamine response status and then compared in terms of grey matter volume (GMV) changes, among 10 hippocampal regions, over 6 and 10 weeks. Mixed ANOVAs were used to analyse interactions between time and group. Post treatment analysis revealed a significant main effect of group for three left hippocampal GMVs as well in the left and right whole hippocampus. Ketamine acute responders (Week 6) showed increased GMVs in both left and right whole hippocampus and in three subfields compared to acute non-responders, across all three timepoints, suggesting that pre-treatment increased hippocampal GMVs (particularly left hemisphere) may be predictive biomarkers of acute treatment response. Future studies should further investigate the potential of hippocampal volumes as a biomarker of ketamine treatment response.


Assuntos
Ketamina , Suicídio , Humanos , Ketamina/farmacologia , Hipocampo , Lobo Temporal , Imageamento por Ressonância Magnética/métodos , Tamanho do Órgão
17.
Exp Cell Res ; 433(2): 113820, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37879549

RESUMO

The Warburg effect links growth and glycolysis in cancer. A key purpose of the Warburg effect is to generate glycolytic intermediates for anabolic reactions, such as nucleotides → RNA/DNA and amino acids → protein synthesis. The aim of this study was to investigate whether a similar 'glycolysis-for-anabolism' metabolic reprogramming also occurs in hypertrophying skeletal muscle. To interrogate this, we first induced C2C12 myotube hypertrophy with IGF-1. We then added 14C glucose to the differentiation medium and measured radioactivity in isolated protein and RNA to establish whether 14C had entered anabolism. We found that especially protein became radioactive, suggesting a glucose → glycolytic intermediates → non-essential amino acid(s) → protein series of reactions, the rate of which was increased by IGF-1. Next, to investigate the importance of glycolytic flux and non-essential amino acid synthesis for myotube hypertrophy, we exposed C2C12 and primary mouse myotubes to the glycolysis inhibitor 2-Deoxy-d-glucose (2DG). We found that inhibiting glycolysis lowered C2C12 and primary myotube size. Similarly, siRNA silencing of PHGDH, the key enzyme of the serine biosynthesis pathway, decreased C2C12 and primary myotube size; whereas retroviral PHGDH overexpression increased C2C12 myotube size. Together these results suggest that glycolysis is important for hypertrophying myotubes, which reprogram their metabolism to facilitate anabolism, similar to cancer cells.


Assuntos
Fator de Crescimento Insulin-Like I , Neoplasias , Animais , Camundongos , Fator de Crescimento Insulin-Like I/metabolismo , Fosfoglicerato Desidrogenase/genética , Fosfoglicerato Desidrogenase/metabolismo , Fosfoglicerato Desidrogenase/farmacologia , Fibras Musculares Esqueléticas/metabolismo , Neoplasias/metabolismo , RNA/metabolismo , Hipertrofia/metabolismo , Glucose/farmacologia , Aminoácidos/genética , Aminoácidos/metabolismo , Aminoácidos/farmacologia
18.
Clin Case Rep ; 11(10): e8032, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37830060

RESUMO

Key Clinical Message: Poncet's disease is an acute onset reactive polyarthritis associated with tuberculosis infection. Although uncommon, the diagnosis should be considered among patients presenting with symmetrical polyarthritis in tuberculosis-endemic regions. Abstract: This is a case report of Poncet's disease presenting as bilateral knee and wrist pain associated with swelling. Joint x-rays and immunological assays were normal. A chest x-ray and Gene-Xpert diagnosed tuberculosis. A complete resolution of symptoms was attained following the completion of antituberculous therapy regimen.

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