It is being realized that identification of subgroups within normal controls corresponding to contrasting disease susceptibility is likely to lead to more effective predictive marker discovery. We ...have previously used the Ayurvedic concept of Prakriti, which relates to phenotypic differences in normal individuals, including response to external environment as well as susceptibility to diseases, to explore molecular differences between three contrasting Prakriti types: Vata, Pitta, and Kapha. EGLN1 was one among 251 differentially expressed genes between the Prakriti types. In the present study, we report a link between high-altitude adaptation and common variations rs479200 (C/T) and rs480902 (T/C) in the EGLN1 gene. Furthermore, the TT genotype of rs479200, which was more frequent in Kapha types and correlated with higher expression of EGLN1, was associated with patients suffering from high-altitude pulmonary edema, whereas it was present at a significantly lower frequency in Pitta and nearly absent in natives of high altitude. Analysis of Human Genome Diversity Panel-Centre d’Etude du Polymorphisme Humain (HGDP-CEPH) and Indian Genome Variation Consortium panels showed that disparate genetic lineages at high altitudes share the same ancestral allele (T) of rs480902 that is overrepresented in Pitta and positively correlated with altitude globally (P < 0.001), including in India. Thus, EGLN1 polymorphisms are associated with high-altitude adaptation, and a genotype rare in highlanders but overrepresented in a subgroup of normal lowlanders discernable by Ayurveda may confer increased risk for high-altitude pulmonary edema.
Introduction: Oral squamous cell carcinoma (OSCC) comprises one of the largest subsets of cancers with a tendency for regional metastasis. Nodal status is a key prognostic indicator in patients with ...OSCC, particularly with N0 neck. Occult metastasis in the form of micrometastasis (MM) and isolated tumor cells (ITCs), often goes undetected by routine hematoxylin and eosin (H&E) examination using 1-2 sections for analysis. This limitation could be overcome by combining serial sectioning (SS) with immunohistochemistry (IHC) for the detection of MM and ITC. Pan-cytokeratin (pan-CK) (AE1/AE3) is particularly a useful marker to detect these deposits as their presence has resulted in varied interpretations and different applications of the tumor-node-metastasis system.
Objectives: The objective of the study was to identify a suitable method for detecting MM and ITC in lymph nodes (LNs) of OSCC by combining SS and IHC and to compare it with conventional H&E staining.
Materials and Methods: This laboratory-based, prospective study was conducted on 133 LNs harnessed from ten patients treated with radical neck dissection for primary OSCC. The LNs were subjected to SS at 100 μm intervals. The sections were stained with routine H&E staining, pan-CK and analyzed for MM and ITC according to criteria laid by Hermanek et al.
Statistical Analysis: The obtained data were subjected to statistical analysis using Chi-square test.
Results: The application of combination of SS and IHC using pan-CK (AE1/AE3) in our study revealed the presence of MM and ITC in 2.25% of the LNs diagnosed as negative on routine H&E examination. The detection of these occult metastatic deposits resulted in upstaging of 33.33% of the patients.
Conclusion: In the view of crucial role of occult LN metastasis in prognosis and survival of OSCC patients with N0 neck, diagnostic tools such as IHC staining, particularly with pan-CK (AE1/AE3), combined with SS should be preferred over conventional methods as they result in upstaging, thus sparing the low-risk patients the morbidity of unnecessary treatment.
It has been long thought that hyperactivation of N-methyl-
d-aspartate (NMDA) receptors underlies neurological decline after traumatic brain injury. However, all clinical trials with NMDA receptor ...antagonists failed. Since NMDA receptors are down-regulated from 4
h to 2
weeks after brain injury, activation at 24
h, rather than inhibition, of these receptors, was previously shown to be beneficial in mice. Here, we tested the therapeutic window, dose regimen and mechanism of action of the NMDA receptor partial agonist
d-cycloserine (DCS) in traumatic brain injury. Male mice were subjected to trauma using a weight-drop model, and administered 10
mg/kg (i.p.) DCS or vehicle once (8, 16, 24, or 72
h) twice (24 and 48
h) or three times (24, 48 and 72
h). Functional recovery was assessed for up to 60
days, using a Neurological Severity Score that measures neurobehavioral parameters. In all groups in which treatment was begun at 24 or 72
h neurobehavioral function was significantly better than in the vehicle-treated groups. Additional doses, on days 2 and 3 did not further improve recovery. Mice treated at 8
h or 16
h post injury did not differ from the vehicle-treated controls. Co-administration of the NMDA receptor antagonist MK-801 completely blocked the protective effect of DCS given at 24
h. Infarct volume measured by 2,3,5-triphenyltetrazolium chloride staining at 48
h or by cresyl violet at 28
days was not affected by DCS treatment. Since DCS is used clinically for other indications, the present study offers a novel approach for treating human traumatic brain injury with a therapeutic window of at least 24
h.
To assess the oral health and related practices of a group of illicit drug users in Delhi, India; to compare with that of non-drug users; and to assess the impact of illicit drug use on oral health.
...Cross-sectional study. Comparison was made with non-drug users to investigate any differences in oral health between illicit drug users and general population.
Illicit drug users attending a drug dependence treatment clinic in Delhi (n=126). Equal number of non-drug users attending other outpatient departments in the same setting.
Oral health practices assessed using structured questionnaire; dental caries, periodontal status and oral mucosa assessed using World Health Organization 2004 criteria; oral hygiene assessed using OHI-S.
Mean DMFT and OHI-S scores amongst the drug users were 3.48 and 3.80, respectively. Bleeding, shallow pockets and deep pockets were found as the highest CPI finding in 42%, 44% and 12% of drug users respectively. Premalignant states of leukoplakia and OSMF were diagnosed in 13% and 4% of drug users respectively. Significant differences were found between drug users and non-drug users with respect to oral hygiene practices; DMFT, OHI-S, CPI scores; and leukoplakia. In multivariate analysis, illicit drug use was significantly associated with CPI highest score (OR = 2.21, 95% CI 1.08-4.52).
The illicit drug users had significantly poorer oral hygiene practices, oral hygiene and periodontal health; higher caries experience; and higher prevalence of leukoplakia as compared to non-drug users. The findings of the study suggest that illicit drug use is independently associated with poor periodontal health.
Summary Healthcare-associated infections (HAIs) are an important cause of morbidity and mortality among critically ill patients of all age groups. This prospective surveillance study was performed to ...estimate the burden of HAIs in a paediatric intensive care unit (PICU) of a developing country. During the 12-month study, 187 patients were treated in the PICU for ≥48 h, of whom 36 patients had 44 episodes of HAIs. The crude infection rate and incidence density (ID) of HAI were 19.3/100 patients and 21/1,000 patient-days, respectively. Of the 44 episodes of HAI, 27 (61%) were healthcare-associated pneumonia (HAP), 12 (27%) were bloodstream infections (HA-BSI) and four (9%) were urinary tract infections. Mean length of stay and mortality were significantly higher in patients who developed an HAI 25 vs 7 days ( P < 0.0001) and 50% vs 27.8% ( P < 0.005), respectively. Acinetobacter spp. were the commonest infecting bacteria in both HAP and HA-BSI. For developing countries, active surveillance is essential to reduce the burden of HAIs in high risk groups.
ABSTRACT
A 28-year-old male patient presented to us with bilateral frontal hyperostosis associated with a small unilateral frontal intracranial meningioma. He underwent successful excision of the ...involved bone and repair of the large cranial defect using a titanium mesh. Histological examination revealed tumor infiltration of the overlying bone. Surgical challenges in the management of such a case are also discussed.
PDF
