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Fulltext Ischial Tuberosity Tuberculosis : An Unusual Location andPresented as Chronic Gluteal Abscess

Krishnan, H., Yoon, T.R., Park, K.S.

Malays Orthop J, 2010;4(1):42-45.
MyJurnal

This case report describes an unusual case of extrapulmonary tuberculosis of the ischial tuberosity presenting with chronic gluteal pain of 4 years duration. The patient presented when the pain became intolerable; at that time, the ischial tuberosity was debrided and curetted while incision and drainage were used to treat the gluteal abscess. Antituberculosis chemotherapy was administered (for a period of one year) following histopathological confirmation of tuberculosis. At four yearspostoperatively, the patient has no pain and is symptom free. Furthermore, radiographs shows that the right ischial tuberosity osteomyelitis has healed. Prompt diagnosis and treatment resulted in a good clinical outcome in this patient.
Fulltext Bipolar Hemiarthroplasty in Elderly Patients Presenting WithDisplaced Intracapsular Femoral Neck Fractures ..

Krishnan, H., Yoon, T.R., Park, K.S.

Malays Orthop J, 2010;4(1):26-31.
MyJurnal

This retrospective study was undertaken to analyze perioperative parameters, functional outcomes and complications of cemented versus uncemented bipolar hemiarthroplasty in elderly patients presenting with displaced intracapsular femoral neck fracture. The authors reviewed 17 patients that underwent cemented bipolar hemiarthroplasty and 21 patients that underwent uncemented bipolar hemiarthroplasty. The mean follow-up duration in the cemented and uncemented group was 29.9 and 30.5 months respectively. Intraoperative and postoperative blood loss was higher in the cemented group. On the last follow-up the mean HHS was 74.7 in the cemented group and 84.2 in the uncemented group. No statistically significant difference was evident in the pain score. In summary, bipolar hemiarthroplasty was found to be a good option for displaced intracapsular femoral neck fractures, and overall outcome was marginally better in the uncemented group in terms of postoperative of blood loss and functional outcome at last follow up.
A potent anticoagulant hybrid of snake venom derived FIX-binding protein and anti-factor IX RNA aptamer: Assessed by in-silico and electrochemical analyses

Krishnan H, Gopinath SCB

Int J Biol Macromol, 2023 Aug 30;247:125740.
PMID: 37423441 DOI: 10.1016/j.ijbiomac.2023.125740

Anticoagulant therapies are crucial in the management of surgical complications as well as the prophylaxis of thrombosis. Many studies are being conducted on the Habu snake-venom anticoagulant, FIX-binding protein (FIX-Bp), for its greater potency and strong affinity to FIX clotting factor. On the other hand, the capacity to promptly reverse such acute anticoagulation is equally important. Combining a reversible anticoagulant with FIX-Bp may be advantageous in maintaining the balance between adequate anticoagulation and repealing when necessary. In this study, authors integrated FIX-Bp and RNA aptamer-based anticoagulants into a single target, FIX clotting factor, in order to achieve a robust anticoagulant effect. An in-silico and electrochemical approach were used to investigate the combination of FIX-Bp and RNA aptamers as a bivalent anticoagulant and to verify the competing or predominant binding sites of each anticoagulant. The in-silico analysis discovered that both the venom- and aptamer-anticoagulant had a strong affinity for the FIX protein at the Gla-domain and EGF-1 domain by holding 9 conventional hydrogen bonds with the binding energy of -34.859 kcal/mol. The electrochemical technique verified that both anticoagulants had different binding sites. The impedance load upon RNA aptamer binding to FIX protein was 14 %, whereas the addition of FIX-Bp caused a significant impedance rise of 37 %. This indicates that the addition of aptamers prior to FIX-Bp is a promising strategy for the conception of a hybrid anticoagulant.
Molecularly imprinted polymer amalgamation on narrow-gapped Archimedean-spiral interdigitated electrodes: resistance to electrolyte fouling in acidic medium

Krishnan H, Gopinath SCB, Md Arshad MK, Zulhaimi HI, Ramanathan S

Mikrochim Acta, 2021 03 31;188(4):144.
PMID: 33791872 DOI: 10.1007/s00604-021-04794-1

A conventional photolithography technique was used to fabricate three types of Archimedean-spiral interdigitated electrodes (AIDEs) containing concentric interlocking electrodes with different electrode and gap sizes, i.e., 150 μm (D1), 100 μm (D2), and 50 μm (D3). The precision of the fabrication was validated by surface topography using scanning electron microscopy, high power microscopy, 3D-nano profilometry, and atomic force microscopy. These AIDEs were fabricated with a tolerance of ± 6 nm in dimensions. The insignificant current variation at the pico-ampere range for all bare AIDEs further proved the reproducibility of the device. The large gap sized AIDE (D1) is insensitive to acidic medium, whereas D2 and D3 are insensitive to alkali medium. D2 was the best with regard to its electrical characterization. Furthermore, uniformly synthesized molecularly imprinted polymer (MIP) nanoparticles prepared with human blood clotting factor IX and its aptamer were in the size range 140 to 160 nm, attached on the sensing surface and characterized. The average thickness of deposited MIP film was 1.7 μm. EDX data shows the prominent peaks for silicon and aluminum substrates as 61.79 and 22.52%, respectively. The MIP nanoparticles-deposited sensor surface was characterized by applying it in electrolyte solutions, and smooth curves with the current flow were observed at pH lower than 8 and discriminated against alkali media. This study provides a new MIP amalgamated AIDE with nano-gapped fingers enabling analysis of other biomaterials due to its operation in an ideal buffer range.
Orthostatic hypotension in Parkinson's disease: Sit-to-stand vs. supine-to-stand protocol and clinical correlates

Lim KB, Lim SY, Hor JW, Krishnan H, Mortadza F, Lim JL, et al.

Parkinsonism Relat Disord, 2024 Apr 22;123:106980.
PMID: 38657381 DOI: 10.1016/j.parkreldis.2024.106980

BACKGROUND: Screening for orthostatic hypotension (OH) is integral in Parkinson's disease (PD) management, yet evidence-based guidelines on best practice methods for diagnosing OH in PD are lacking.
METHODS: We investigated the frequency and correlates of OH, symptomatic OH, and neurogenic OH, in a large consecutively recruited PD cohort (n = 318), and compared the diagnostic performance of the sit-to-stand vs. the supine-to-stand blood pressure (BP) test. We evaluated the utility of continuous BP monitoring and tilt table testing in patients with postural symptoms or falls who were undetected to have OH with clinic-based BP measurements. Disease severity, fluid intake, orthostatic and overactive bladder symptoms, falls, comorbidities and medication history were evaluated.
RESULTS: Patients' mean age was 66.1 ± 9.5years, with mean disease duration 7.8 ± 5.5years. OH frequency was 35.8 % based on the supine-to-stand test. OH in PD was significantly associated with older age, lower body mass index, longer disease duration, worse motor, cognitive and overactive bladder symptoms and functional disabilities, falls, and lower fluid intake. A similar profile was seen with asymptomatic OH. Three quarters of OH were neurogenic, with the majority also having supine hypertension. The sit-to-stand test had a sensitivity of only 0.39. One quarter of patients were additionally diagnosed with OH during continuous BP monitoring.
CONCLUSIONS: The sit-to-stand test substantially underdiagnoses OH in PD, with the important practice implication that supine-to-stand measurements may be preferred. Screening for OH is warranted even in asymptomatic patients. Adequate fluid intake, treatment of urinary dysfunction and falls prevention are important strategies in managing PD patients with OH.
Fulltext Mechanisms of environmental chemicals that enable the cancer hallmark of evasion of growth suppression

Nahta R, Al-Mulla F, Al-Temaimi R, Amedei A, Andrade-Vieira R, Bay SN, et al.

Carcinogenesis, 2015 Jun;36 Suppl 1:S2-18.
PMID: 26106139 DOI: 10.1093/carcin/bgv028

As part of the Halifax Project, this review brings attention to the potential effects of environmental chemicals on important molecular and cellular regulators of the cancer hallmark of evading growth suppression. Specifically, we review the mechanisms by which cancer cells escape the growth-inhibitory signals of p53, retinoblastoma protein, transforming growth factor-beta, gap junctions and contact inhibition. We discuss the effects of selected environmental chemicals on these mechanisms of growth inhibition and cross-reference the effects of these chemicals in other classical cancer hallmarks.
Fulltext Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Goodson WH, Lowe L, Carpenter DO, Gilbertson M, Manaf Ali A, Lopez de Cerain Salsamendi A, et al.

Carcinogenesis, 2015 Jun;36 Suppl 1:S254-96.
PMID: 26106142 DOI: 10.1093/carcin/bgv039

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.