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Article ; Online: Biologic Therapies in Stress Fractures: Current Concepts.

Jacob, George / Shimomura, Kazunori / Nakamura, Norimasa

Journal of ISAKOS : joint disorders & orthopaedic sports medicine

2024

Abstract: Stress fractures, a common overuse injury in physically active individuals, present a significant challenge for athletes and military personnel. Patients who sustain stress fractures have demanding training regimes, where periods of rest and ... ...

Abstract	Stress fractures, a common overuse injury in physically active individuals, present a significant challenge for athletes and military personnel. Patients who sustain stress fractures have demanding training regimes, where periods of rest and immobilisation have unacceptable negative consequences on sport goals and finances. Aside from being an overuse injury, there are various contributing risk factors that put certain individuals at risk of a stress fracture. The main two being nutritional deficiencies and hormonal variations which have significant effects on bone metabolism and turnover. Historically, treatment of stress fractures focused on conservative strategies such as rest and immobilisation. Calcium and vitamin D deficiencies have been closely linked to stress fractures and so over time supplementation has also played a role in treatment. With the introduction of biologics into orthopaedics, newer treatment strategies have been applied accelerate fracture healing and perhaps improve fracture callus quality. If such therapies can reduce, time spent away from sport and activity, it would be ideal for treating stress fractures. This article aims to offers insights into the evolving landscape of stress fracture management. It investigates the pre-clinical evidence and available published clinical applications. Though fracture healing is well understood, the role of biologics for fracture healing is still indeterminate. Available literature for the use of biologics therapies in stress fractures is restricted and most reports have used biologics as a supplement to surgical fixation in subjects in studies that lack control groups. Randomised control trials have been proposed and registered by a few groups with results awaited. Assessing individuals for risk factors, addressing hormonal imbalances and nutritional deficiencies seem an effective approach to addressing the burden of stress fractures. We await better designed trials and studies to accurately determine the clinical benefit of adding biologics to management of these injuries.
Language	English
Publishing date	2024-04-15
Publishing country	England
Document type	Journal Article
ISSN	2059-7762
ISSN (online)	2059-7762
DOI	10.1016/j.jisako.2024.04.008
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: TREM2 Agonism with a Monoclonal Antibody Attenuates Tau Pathology and Neurodegeneration

Michael Fassler / Clara Benaim / Jacob George

Cells, Vol 12, Iss 1549, p

2023 Volume 1549

Abstract: TREM2 is a membrane receptor expressed on microglia that plays a pivotal role in the organization and function of these innate immune cell components within the neurodegenerated brain. Whereas TREM2 deletion has been studied extensively in experimental ... ...

Abstract	TREM2 is a membrane receptor expressed on microglia that plays a pivotal role in the organization and function of these innate immune cell components within the neurodegenerated brain. Whereas TREM2 deletion has been studied extensively in experimental beta-amyloid and Tau-based models of Alzheimer’s disease, its engagement, and subsequent agonism have not been tested in the context of Tau pathology. Herein, we explored the effects of Ab-T1, an agonistic TREM2 monoclonal antibody on Tau uptake, phosphorylation, seeding, and spreading as well as its therapeutic efficacy in a Tauopathy model. Ab-T1 enhanced the uptake of misfolded Tau to microglia and induced a non-cell autonomous attenuation of spontaneous Tau seeding and phosphorylation in primary neurons from human Tau transgenic mice. Ex vivo, incubation with Ab-T1 led to a significant reduction in the seeding of Tau pathology in the hTau murine organoid brain system. Systemic administration of Ab-T1 resulted in reduced Tau pathology and propagation when hTau was stereotactically injected into the hemispheres of hTau mice. Intraperitoneal treatment with Ab-T1 lead to attenuation of cognitive decline in the hTau mice that was associated with reduced neurodegeneration and synaptic preservation with amelioration of the global neuroinflammatory program. Collectively, these observations show that TREM2 engagement with an agonistic antibody result in reduced Tau burden concomitant with attenuated neurodegeneration ascribed to the education of resident microglia. These results may suggest that despite the opposing results with regard to the effect of TREM2 knockout in experimental Tau-based model systems, receptor engagement and activation by Ab-T1 appears to possess beneficial effects with respect to the various mechanisms mediating Tau-driven neurodegeneration.
Keywords	TREM2 ; tauopathy ; neurodegeneration ; neuroinflammation ; Alzheimer’s ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Single Chain Fragment Variant Binding Misfolded Alpha-Synuclein Exhibits Neuroprotective and Antigen-Specific Anti-Inflammatory Properties

Michael Fassler / Clara Benaim / Jacob George

Cells, Vol 11, Iss 3822, p

2022 Volume 3822

Abstract: Introduction. Alpha synuclein (αSyn) misfolding plays a requisite role in the pathogenesis of synucleinopathies. Direct toxicity to neurons, triggering neuroinflammation as well as the spreading and seeding of αSyn pathology are essential pathogenetic ... ...

Abstract	Introduction. Alpha synuclein (αSyn) misfolding plays a requisite role in the pathogenesis of synucleinopathies. Direct toxicity to neurons, triggering neuroinflammation as well as the spreading and seeding of αSyn pathology are essential pathogenetic underlying mechanisms. Immunotherapy in experimental Parkinson’s disease (PD) has been shown to be consistently effective in preclinical models, yet the initial clinical trials with monoclonal antibodies (mAbs) yielded marginal results if any. Aiming to overcome some of the limitation of this approach, we aimed to select an αSyn binding scFv antibody format and test it in multiple experimental PD in vivo models. Methods. We cloned the lead αSyn scFv based on preselection of human phage display libraries of human Fab. The selected of scFv targeting both oligomers and pre-formed fibrils (PFF) of αSyn were tested for their ability to protect neurons from triggered toxicity, influence their uptake to microglia, and accelerate misfolded αSyn degradation. The lead scFv- sMB08, was also tested for its ability to impact αSyn aggregation as well as spreading and seeding. Results. sMB08 was shown to protect neurons from misfolded αSyn mediated toxicity, promote its intracellular degradation, and to reduce its uptake by microglia. sMB08 exhibited anti-inflammatory properties, including its ability to attenuate adaptive αSyn autoimmunity and ameliorate proinflammatory cytokine expression in brains of mice stereotactically injected with PFF. Employing three experimental models of PD, intranasal treatment with sMB08 attenuated motoric dysfunction and achieved acceptable brain levels by pharmacokinetic analysis, leading to significant preservation of dopaminergic n neurons. Conclusion: sMB08, a scFv targeting both αSyn oligomers and PFF, due to its small size facilitating paraneural brain penetration and avoidance of nonspecific inflammation, appears as an attractive approach to test in patients with PD by addressing the major mechanisms that mediate misfolded αSyn driven ...
Keywords	synucleinopathies ; immunotherapy ; alpha synuclein ; neurodegeneration ; nose to brain delivery ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: A Blue Print for Neera Supply Chain

Jacob George

Indian Coconut Journal (India)

(Nov 2014) , Issue (7)

Keywords	NOIX DE COCO ; COCO ; COCONUTS
Language	English
Document type	Article
ISSN	0970-0579
Database	AGRIS - International Information System for the Agricultural Sciences and Technology

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Article ; Online: Halitosis – a Review

Jacob George

South Sudan Medical Journal, Vol 7, Iss 1, Pp 12-

2014 Volume 14

Abstract: Halitosis (bad breath) is an oral condition characterized by unpleasant odours from the oral cavity. It is estimated to be the third most frequent reason for people seeking dental care, following tooth decay and periodontal disease [1]. In 90% of cases ... ...

Abstract	Halitosis (bad breath) is an oral condition characterized by unpleasant odours from the oral cavity. It is estimated to be the third most frequent reason for people seeking dental care, following tooth decay and periodontal disease [1]. In 90% of cases the causes of halitosis arise in the mouth and caused by deep carious lesions, periodontal diseases, oral infections, peri-implant diseases, pericoronitis, mucosal ulcerations, impacted food or debris, factors causing decreased salivary flow rate and tongue coating [2]. The tongue is a major site of oral malodour
Keywords	Medicine ; R ; Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2014-02-01T00:00:00Z
Publisher	South Sudan Doctors' Association
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Vitiligo progression in a patient undergoing romosozumab treatment for osteoporosis.

Trepanowski, Nicole / Yim, Rebecca M / Wetstone, Rachel / MacDonald, Elizabeth / Servattalab, Sarah / Jacob-George, Subin / Harris, John E

JAAD case reports

2023 Volume 42, Page(s) 26–30

Language	English
Publishing date	2023-10-11
Publishing country	United States
Document type	Case Reports
ZDB-ID	2834220-3
ISSN	2352-5126
ISSN	2352-5126
DOI	10.1016/j.jdcr.2023.09.033
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Total Knee Arthroplasty in Paget's Disease using 3D-Printed Patient-Specific Femoral Jig - A Case Report.

Sathikumar, Aravind Sai / Jacob, George / Varghese, Jacob / Mathew, Vivek

Journal of orthopaedic case reports

2023 Volume 13, Issue 8, Page(s) 84–88

Abstract: Introduction: Patients with Paget's disease develop abnormal bony anatomy which can result in significantly altered lower limb alignment predisposing them to early secondary osteoarthritis. Due to the severe extra-articular deformity, total knee ... ...

Abstract	Introduction: Patients with Paget's disease develop abnormal bony anatomy which can result in significantly altered lower limb alignment predisposing them to early secondary osteoarthritis. Due to the severe extra-articular deformity, total knee arthroplasty (TKA) in these patients is challenging. Conventional knee arthroplasty using intramedullary guides is not an option and can lead to erroneous limb alignment postoperatively. Patient-specific instrumentation (PSI) is a simple solution in such complex primary knee arthroplasty. Case report: A 70-year-old male patient presented with a severe left femur deformity and left knee pain. He was diagnosed to have monostotic Paget's disease of the left femur with tricompartmental osteoarthritis of the left knee. After reduction in pathological bone turnover, the patient was planned for a total knee replacement. As a standard intramedullary femoral jig was not applicable due to the femoral deformity, a computed topography-based 3D-printed patient-specific instrument was used. This custom jig was used to define and perform the distal femur cut at 90 degrees to the mechanical axis of the femur in the coronal and sagittal plane. Postoperatively, the patient did well and achieved good function and pain relief. Conclusion: The use of a 3D-printed PSI for complex primary knee arthroplasty is an excellent option with no additional operative time than a conventional knee arthroplasty. Although a robotic or computer-navigated TKA would be an excellent option in this case, we restored the limb alignment using a cost-effective patient-specific femoral jig. This could be a viable option in centers without navigation or robotic arthroplasty.
Language	English
Publishing date	2023-07-21
Publishing country	India
Document type	Case Reports
ZDB-ID	2658169-3
ISSN	2250-0685
ISSN	2250-0685
DOI	10.13107/jocr.2023.v13.i08.3826
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Article ; Online: Comparative evaluation of efficacy of physics forcep and conventional forceps for extraction of maxillary molars.

Bhosale, Tushar N / Bhate, Kalyani / Samuel, Sherwin / Jacob, George

Minerva dental and oral science

2023 Volume 73, Issue 2, Page(s) 75–80

Abstract: Background: Tooth extraction is one of the most commonly performed procedures in dentistry. It is usually a traumatic procedure often resulting in immediate destruction and loss of alveolar bone and surrounding soft tissues. It is the only dental ... ...

Abstract	Background: Tooth extraction is one of the most commonly performed procedures in dentistry. It is usually a traumatic procedure often resulting in immediate destruction and loss of alveolar bone and surrounding soft tissues. It is the only dental procedure which was carried out by dentists in the previous centuries and various instruments have evolved for this procedure over time. Atraumatic extraction is one of the essential dental procedures, as atraumatic extraction leads to proper wound healing and appropriate bone healing. Physics forceps have got a new role in extraction technique, that it makes just one contact point with the tooth as a unique benefit. Physics forceps depends on the physics of rotational power, lever and torque much like a bottle top removal. A study was conducted to evaluate the efficacy of physics forceps and conventional forces in the extraction of maxillary molar. Methods: Eligible participants were adults aged 18-50 diagnosed with grossly decayed maxillary molars with poor endodontic prognosis and willing to participate in the study. Exclusion criteria were as follows: patients with dilacerate roots; patients with systemic diseases like hypertension, diabetes mellitus, thyroid, tuberculosis, epilepsy seizures, COVID-19 positive; patients' non-acceptance to voluntarily participate in research a refusal to sign the informed consent. Parameters such as a crown fracture or root fracture; buccal bone fracture; time taken for extraction and operator ease on the VAS scale are assessed. Results: Results showed that with the use of physics forces, there was very less incidence of crown fracture and no incidence of buccal bone fracture, whereas with the conventional forceps the result showed that in almost all the time taken for extraction was much more in conventional forcep and the operator ease rating was more with conventional forceps. Conclusions: Hence, oral surgeons as well as general practitioner should adapt the use of physics forceps in routine extractions.
MeSH term(s)	Adult ; Humans ; Molar/surgery ; Tooth Extraction ; Surgical Instruments ; Fractures, Bone ; Physics
Language	English
Publishing date	2023-06-16
Publishing country	Italy
Document type	Journal Article
ZDB-ID	3062693-6
ISSN	2724-6337
ISSN (online)	2724-6337
DOI	10.23736/S2724-6329.23.04740-X
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Article ; Online: From MAFLD to hepatocellular carcinoma and everything in between

Sarah Da Won Bae / Jacob George / Liang Qiao / Yuanyuan Ji

Chinese Medical Journal, Vol 135, Iss 5, Pp 547-

2022 Volume 556

Abstract: Abstract. Metabolic (dysfunction) associated fatty liver disease (MAFLD), previously known as non-alcoholic fatty liver disease, is the most common cause of chronic liver disease worldwide. Many risk factors contribute to the pathogenesis of MAFLD with ... ...

Abstract	Abstract. Metabolic (dysfunction) associated fatty liver disease (MAFLD), previously known as non-alcoholic fatty liver disease, is the most common cause of chronic liver disease worldwide. Many risk factors contribute to the pathogenesis of MAFLD with metabolic dysregulation being the final arbiter of its development and progression. MAFLD poses a substantial economic burden to societies, which based on current trends is expected to increase over time. Numerous studies have addressed various aspects of MAFLD from its risk associations to its economic and social burden and clinical diagnosis and management, as well as the molecular mechanisms linking MAFLD to end-stage liver disease and hepatocellular carcinoma. This review summarizes current understanding of the pathogenesis of MAFLD and related diseases, particularly liver cancer. Potential therapeutic agents for MAFLD and diagnostic biomarkers are discussed.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Wolters Kluwer
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Demographic, health, and prognostic characteristics of Australians with liver cancer

David Roder / David Banham / Jacob George / Shelley Rushton / Tracey O’Brien

BMC Public Health, Vol 23, Iss 1, Pp 1-

a cohort study of linked data in New South Wales for informing cancer control

2023 Volume 13

Abstract: Abstract Background Australian age-standardized incidence and death rates for liver cancer are lower than world averages, but increasing as in other economically advanced western countries. World Health Organization emphasizes the need to address ... ...

Abstract	Abstract Background Australian age-standardized incidence and death rates for liver cancer are lower than world averages, but increasing as in other economically advanced western countries. World Health Organization emphasizes the need to address sociodemographic disparities in cancer risk. A more detailed sociodemographic risk profiling was undertaken for liver cancer in New South Wales (NSW) by diagnostic stage, than possible with NSW Cancer Registry (NSWCR) alone, by incorporating linked data from the Australian Bureau of Statistics (ABS). The purpose was to inform targeting and monitoring of cancer services. Methods The ABS manages the Multi-Agency Data Integration Project (MADIP) which includes a wide range of health, educational, welfare, census, and employment data. These data were linked at person level to NSWCR liver cancer registrations for the period post 2016 census to December 2018. De-identified data were analyzed. Sex-specific age-adjusted odds ratios (95%CIs) of liver cancer were derived using logistic regression by age, country of birth, residential remoteness, proficiency in spoken English, household income, employment status, occupation type, educational attainment, sole person household, joblessness, socioeconomic status, disability status, multimorbidity, and other health-related factors, including GP consultations. These data complement the less detailed sociodemographic data available from the NSWCR, with alignment of numerators and population denominators for accurate risk assessment. Results Results indicate liver cancer disproportionately affects population members already experiencing excess social and health disadvantage. Examples where 95% confidence intervals of odds ratios of liver cancer were elevated included having poor English-speaking proficiency, limited education, housing authority tenancy, living in sole-person households, having disabilities, multiple medicated conditions, and being carers of people with a disability. Also, odds of liver cancer were higher in more remote ...
Keywords	Liver cancer ; Risk factors – demographic factors ; Data linkage ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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