Beta activity in human anterior cingulate cortex mediates reward biases.

The rewards that we get from our choices and actions can have a major influence on our future behavior. Understanding how reward biasing of behavior is implemented in the brain is important for many reasons, including the fact that diminution in reward biasing is a hallmark of clinical depression. We hypothesized that reward biasing is mediated by the anterior cingulate cortex (ACC), a cortical hub region associated with the integration of reward and executive control and with the etiology of depression. To test this hypothesis, we recorded neural activity during a biased judgment task in patients undergoing intracranial monitoring for either epilepsy or major depressive disorder. We found that beta (12-30 Hz) oscillations in the ACC predicted both associated reward and the size of the choice bias, and also tracked reward receipt, thereby predicting bias on future trials. We found reduced magnitude of bias in depressed patients, in whom the beta-specific effects were correspondingly reduced. Our findings suggest that ACC beta oscillations may orchestrate the learning of reward information to guide adaptive choice, and, more broadly, suggest a potential biomarker for anhedonia and point to future development of interventions to enhance reward impact for therapeutic benefit.

Insula uses overlapping codes for emotion in self and others.

In daily life, we must recognize others' emotions so we can respond appropriately. This ability may rely, at least in part, on neural responses similar to those associated with our own emotions. We hypothesized that the insula, a cortical region near the junction of the temporal, parietal, and frontal lobes, may play a key role in this process. We recorded local field potential (LFP) activity in human neurosurgical patients performing two tasks, one focused on identifying their own emotional response and one on identifying facial emotional responses in others. We found matching patterns of gamma- and high-gamma band activity for the two tasks in the insula. Three other regions (MTL, ACC, and OFC) clearly encoded both self- and other-emotions, but used orthogonal activity patterns to do so. These results support the hypothesis that the insula plays a particularly important role in mediating between experienced vs. observed emotions.

Assessing the Burden of COVID-19 among Children Aged 6-14 Years in Karnataka, India: A Cross-sectional Survey.

Background: India experienced three coronavirus disease (COVID-19) waves, with the third attributed to the highly contagious Omicron variant. Before the national vaccination rollout for children above 6, understanding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) positivity in the pediatric population was essential. This study aims to assess the burden of Covid-19 infection and to estimate the seroprevalence in children aged 6 to 14 years in the state of Karnataka. Material and Methods: We surveyed 5,358 children aged 6-14 across Karnataka using 232 health facilities, from June 6 to 14, 2022. We determined the sample size using the PPS (Population Proportional to Size) technique and employed cluster sampling. We tested all participants for SARS-CoV-2 IgG with an enzyme-linked immunosorbent assay (ELISA) kit and SARS-CoV-2 RNA with reverse transcription-polymerase chain reaction (RT-PCR). We sequenced samples with a cycle threshold (CT) value below 25 using whole genomic sequencing (WGS). Result: We found an adjusted seroprevalence of IgG at 75.38% statewide, and we found 0.04% of children RT-PCR positive for COVID-19. We determined a case-to-infection ratio of 1:37 and identified the SARS-CoV-2 strains as Omicron, BA.5, and BA.2.10. Conclusion: The study showed a high seroprevalence of IgG among children with low active infection. Omicron, BA. 5, and BA. 2.10 variants were detected through WGS.

Lipotype acquisition during neural development is not recapitulated in stem cell-derived neurons.

During development, different tissues acquire distinct lipotypes that are coupled to tissue function and homeostasis. In the brain, where complex membrane trafficking systems are required for neural function, specific glycerophospholipids, sphingolipids, and cholesterol are highly abundant, and defective lipid metabolism is associated with abnormal neural development and neurodegenerative disease. Notably, the production of specific lipotypes requires appropriate programming of the underlying lipid metabolic machinery during development, but when and how this occurs is unclear. To address this, we used high-resolution MSALL lipidomics to generate an extensive time-resolved resource of mouse brain development covering early embryonic and postnatal stages. This revealed a distinct bifurcation in the establishment of the neural lipotype, whereby the canonical lipid biomarkers 22:6-glycerophospholipids and 18:0-sphingolipids begin to be produced in utero, whereas cholesterol attains its characteristic high levels after birth. Using the resource as a reference, we next examined to which extent this can be recapitulated by commonly used protocols for in vitro neuronal differentiation of stem cells. Here, we found that the programming of the lipid metabolic machinery is incomplete and that stem cell-derived cells can only partially acquire a neural lipotype when the cell culture media is supplemented with brain-specific lipid precursors. Altogether, our work provides an extensive lipidomic resource for early mouse brain development and highlights a potential caveat when using stem cell-derived neuronal progenitors for mechanistic studies of lipid biochemistry, membrane biology and biophysics, which nonetheless can be mitigated by further optimizing in vitro differentiation protocols.

Youth focused life skills training and counselling services program-An inter-sectoral initiative in India: Program development and preliminary analysis of factors affecting life skills.

OBJECTIVES: This paper describes the methodology of developing and implementation of a youth focused life skills training and counselling services programme (LSTCP) and assessment of factors associated with life skills of participants pre-training. DESIGN: Development of all aspects of LSTCP (modules, methods and evaluation) was through a consultative process. Experiential learning based facilitation was decided as the approach for training participants. A quasi-experimental design with pre, post and follow-up assessment post-training was finalised. Data collection was done using specifically developed semi-structured self-administered questionnaire. RESULTS: Multivariable logistic regression with life skills as outcome and various exposure variables was performed. About 2/3rd of participants had high level of life skills (68%). Increased score of extraversion (AOR = 1.57,95% CI = 1.32-1.85), agreeableness (AOR = 1.42,95% CI = 1.16-1.73), conscientiousness (AOR = 1.9,95% CI = 1.55-2.33), physical (AOR = 1.03,95% CI = 1.01-1.04), environmental (AOR = 1.02,95% CI = 1.004-1.03) and social quality of life (AOR = 1.01,95% CI = 1.006-1.02) were associated with high life skills score. Higher score of neuroticism (AOR = 0.66,95% CI = 0.53-0.79) was associated with low life skills score. CONCLUSION: The results presented provide an opportunity to understand the evolution of factors affecting life skills during the follow-up of this study. This study throws light on development of LSTCP for apparently healthy population in a setting like India and its states.

Decoding Depression Severity From Intracranial Neural Activity.

BACKGROUND: Disorders of mood and cognition are prevalent, disabling, and notoriously difficult to treat. Fueling this challenge in treatment is a significant gap in our understanding of their neurophysiological basis. METHODS: We recorded high-density neural activity from intracranial electrodes implanted in depression-relevant prefrontal cortical regions in 3 human subjects with severe depression. Neural recordings were labeled with depression severity scores across a wide dynamic range using an adaptive assessment that allowed sampling with a temporal frequency greater than that possible with typical rating scales. We modeled these data using regularized regression techniques with region selection to decode depression severity from the prefrontal recordings. RESULTS: Across prefrontal regions, we found that reduced depression severity is associated with decreased low-frequency neural activity and increased high-frequency activity. When constraining our model to decode using a single region, spectral changes in the anterior cingulate cortex best predicted depression severity in all 3 subjects. Relaxing this constraint revealed unique, individual-specific sets of spatiospectral features predictive of symptom severity, reflecting the heterogeneous nature of depression. CONCLUSIONS: The ability to decode depression severity from neural activity increases our fundamental understanding of how depression manifests in the human brain and provides a target neural signature for personalized neuromodulation therapies.

Smoked tobacco dependence and its correlates among participants attending life skills training and counselling services programme across Karnataka (2017-2022).

Introduction: Indian National Mental Health Survey reports an alarming prevalence of 20.9% for tobacco dependence in India. Dependence on smoked tobacco can be prevented by thorough knowledge of the risk factors associated with it. Objectives: To estimate the prevalence and identify the factors associated with smoked tobacco dependence among participants attending the life skills training and counselling services programme (LSTCSP) across Karnataka from 2017 to 2022. Materials and Methods: Pretraining data of 3104 participants from training programmes between 2017 and 2022 were utilised. Univariate and multivariable logistic regression analysis was performed based on a conceptual framework with various hypothesised exposure variables and smoked tobacco dependence as outcome. Results: The overall prevalence of smoked tobacco dependence among LSTCSP participants who used smoked tobacco products was 59.4%. Ever use of smokeless tobacco products (Adjusted odds ratio (AOR) =2.05, 95% CI: 1.11-3.78) and screening positive for symptoms of generalised anxiety (AOR = 2.53, 95% CI: 1.32-4.84) significantly increased the odds of smoked tobacco dependence, whereas making decisions collectively in the family (AOR = 0.35, 95% CI: 0.18-0.66) and individuals with increased score for neurotic personality traits (AOR = 0.64, 95% CI: 0.44-0.93) were the factors associated with reduced odds of smoked tobacco dependence. Conclusion: The identified risk factors associated with smoked tobacco dependence are important to develop tobacco control programmes as well as in preventing its onset. With the risk factors for smoked tobacco dependence identified, the results of this study have implications for health promotion and prevention programmes as well as cessation programmes related to smoked tobacco dependence, within India and similar countries.

Effectiveness and Factors Associated with Improved Life Skill Levels of Participants of a Large-Scale Youth-Focused Life Skills Training and Counselling Services Program (LSTCP): Evidence from India.

(1) Background: To empower and facilitate mental health promotion for nearly 18 million youth, a pioneering state-wide Life Skills Training and Counselling Services Program (LSTCP) was implemented in Karnataka, India. This study assesses the changes in life skills scores, level of life skills and factors associated with increased life skills among participants of the LSTCP. (2) Method: This pre-post study design was conducted on 2669 participants who underwent a six-day structured LSTCP. Changes in mean life skills scores and level of life skill categories pre- and post-LSTCP were assessed. Multivariate logistic regression was performed to assess the factors associated with increases in life skills. (3) Results: The LSTCP resulted in significant changes in life skill scores and level of life skills, indicating the effectiveness of the training. All life skill domains, except empathy and self-awareness, increased post-training. There was a positive shift in the level of life skills. Age (AOR = 1.34, CI = 1.11-1.62), gender (AOR = 1.39, CI = 1.15-1.68), education (AOR = 1.44, CI = 1.05-1.97) and physical (AOR = 1.02, CI = 1.01-1.03) and psychological (AOR = 1.02, CI = 1.01-1.03) quality of life was associated with an increase in life skills among participants. (4) Conclusions: The LSTCP is effective in improving the life skills of participants. The LSTCP modules and processes can be used to further train youth and contribute to mental health promotion in the state.

Imaging versus electrographic connectivity in human mood-related fronto-temporal networks.

BACKGROUND: The efficacy of psychiatric DBS is thought to be driven by the connectivity of stimulation targets with mood-relevant fronto-temporal networks, which is typically evaluated using diffusion-weighted tractography. OBJECTIVE: Leverage intracranial electrophysiology recordings to better predict the circuit-wide effects of neuromodulation to white matter targets. We hypothesize strong convergence between tractography-predicted structural connectivity and stimulation-induced electrophysiological responses. METHODS: Evoked potentials were elicited by single-pulse stimulation to two common DBS targets for treatment-resistant depression - the subcallosal cingulate (SCC) and ventral capsule/ventral striatum (VCVS) - in two patients undergoing DBS with stereo-electroencephalographic (sEEG) monitoring. Evoked potentials were compared with predicted structural connectivity between DBS leads and sEEG contacts using probabilistic, patient-specific diffusion-weighted tractography. RESULTS: Evoked potentials and tractography showed strong convergence in both patients in orbitofrontal, ventromedial prefrontal, and lateral prefrontal cortices for both SCC and VCVS stimulation targets. Low convergence was found in anterior cingulate (ACC), where tractography predicted structural connectivity from SCC targets but produced no evoked potentials during SCC stimulation. Further, tractography predicted no connectivity to ACC from VCVS targets, but VCVS stimulation produced robust evoked potentials. CONCLUSION: The two connectivity methods showed significant convergence, but important differences emerged with respect to the ability of tractography to predict electrophysiological connectivity between SCC and VCVS to regions of the mood-related network. This multimodal approach raises intriguing implications for the use of tractography in surgical targeting and provides new data to enhance our understanding of the network-wide effects of neuromodulation.

Age, gender, peers, life skills and quality of life influence risk of cell phone addiction among college teachers in Karnataka, India : a state level epidemiological analysis.

BACKGROUND: Cell phones are an integral part of modern day life and have become companions for individuals irrespective of age, gender and socio-economic status. In this study, we assessed the factors affecting risk of cell phone addiction among teachers attending Life Skills Training and Counselling Services (LSTCS) program in Karnataka. METHODS: This cross sectional secondary data analysis utilised data from baseline assessment of trainees attending a Life Skills Training and Counselling Services program (LSTCP). Various factors hypothesised to be affecting risk of cell phone addiction (outcome) was analysed using univariate and multivariable logistic regression analysis. All the analysis was done using STATA 12.0 software. RESULTS: Multivariable logistic regression analysis was conducted with risk of cell phone addiction as outcome. A conceptual framework of hypothesized exposure variables was developed based on expert consultation and literature review. Overall, data of 1981 participants was utilized. Gender (AOR=1.91; 95% CI=1.27-2.77), number of peers (AOR=1.01; 95 CI=1-1.008) and social quality of life (AOR=1.01; 95% CI=1.00-1.03) were associated with increased risk of cell phone addiction. Age (AOR=0.98; 95%CI=0.96-1.00), empathy (AOR=0.96;95%;CI=0.93-0.99), communication skills(AOR=0.92, 95%;CI=0.88-0.96) and physical quality of life (AOR=0.96; 95% CI=0.95-0.98) were associated with reduced risk of cell phone addiction. CONCLUSIONS: This study on precursors of risk of cell phone addiction, conducted mostly among apparently healthy individuals, provide important insights into interventions to reduce risk of cell phone addiction. The complexity of associations between peers, gender, quality of life and risk of cell phone addiction needs further exploration.

Uncovering biomarkers during therapeutic neuromodulation with PARRM: Period-based Artifact Reconstruction and Removal Method.

Advances in therapeutic neuromodulation devices have enabled concurrent stimulation and electrophysiology in the central nervous system. However, stimulation artifacts often obscure the sensed underlying neural activity. Here, we develop a method, termed Period-based Artifact Reconstruction and Removal Method (PARRM), to remove stimulation artifacts from neural recordings by leveraging the exact period of stimulation to construct and subtract a high-fidelity template of the artifact. Benchtop saline experiments, computational simulations, five unique in vivo paradigms across animal and human studies, and an obscured movement biomarker are used for validation. Performance is found to exceed that of state-of-the-art filters in recovering complex signals without introducing contamination. PARRM has several advantages: (1) it is superior in signal recovery; (2) it is easily adaptable to several neurostimulation paradigms; and (3) it has low complexity for future on-device implementation. Real-time artifact removal via PARRM will enable unbiased exploration and detection of neural biomarkers to enhance efficacy of closed-loop therapies.

Automated and rapid self-report of nociception in transgenic mice.

There are currently no rapid, operant pain behaviors in rodents that use a self-report to directly engage higher-order brain circuitry. We have developed a pain detection assay consisting of a lick behavior in response to optogenetic activation of predominantly nociceptive peripheral afferent nerve fibers in head-restrained transgenic mice expressing ChR2 in TRPV1 containing neurons. TRPV1-ChR2-EYFP mice (n = 5) were trained to provide lick reports to the detection of light-evoked nociceptive stimulation to the hind paw. Using simultaneous video recording, we demonstrate that the learned lick behavior may prove more pertinent in investigating brain driven pain processes than the reflex behavior. Within sessions, the response bias of transgenic mice changed with respect to lick behavior but not reflex behavior. Furthermore, response similarity between the lick and reflex behaviors diverged near perceptual threshold. Our nociceptive lick-report detection assay will enable a host of investigations into the millisecond, single cell, neural dynamics underlying pain processing in the central nervous system of awake behaving animals.

The Case for Adaptive Neuromodulation to Treat Severe Intractable Mental Disorders.

Mental disorders are a leading cause of disability worldwide, and available treatments have limited efficacy for severe cases unresponsive to conventional therapies. Neurosurgical interventions, such as lesioning procedures, have shown success in treating refractory cases of mental illness, but may have irreversible side effects. Neuromodulation therapies, specifically Deep Brain Stimulation (DBS), may offer similar therapeutic benefits using a reversible (explantable) and adjustable platform. Early DBS trials have been promising, however, pivotal clinical trials have failed to date. These failures may be attributed to targeting, patient selection, or the "open-loop" nature of DBS, where stimulation parameters are chosen ad hoc during infrequent visits to the clinician's office that take place weeks to months apart. Further, the tonic continuous stimulation fails to address the dynamic nature of mental illness; symptoms often fluctuate over minutes to days. Additionally, stimulation-based interventions can cause undesirable effects if applied when not needed. A responsive, adaptive DBS (aDBS) system may improve efficacy by titrating stimulation parameters in response to neural signatures (i.e., biomarkers) related to symptoms and side effects. Here, we present rationale for the development of a responsive DBS system for treatment of refractory mental illness, detail a strategic approach for identification of electrophysiological and behavioral biomarkers of mental illness, and discuss opportunities for future technological developments that may harness aDBS to deliver improved therapy.

A methyl 1H double quantum CPMG experiment to study protein conformational exchange.

Protein conformational changes play crucial roles in enabling function. The Carr-Purcell-Meiboom-Gill (CPMG) experiment forms the basis for studying such dynamics when they involve the interconversion between highly populated and sparsely formed states, the latter having lifetimes ranging from ~ 0.5 to ~ 5 ms. Among the suite of experiments that have been developed are those that exploit methyl group probes by recording methyl 1H single quantum (Tugarinov and Kay in J Am Chem Soc 129:9514-9521, 2007) and triple quantum (Yuwen et al. in Angew Chem Int Ed Engl 55:11490-11494, 2016) relaxation dispersion profiles. Here we build upon these by developing a third experiment in which methyl 1H double quantum coherences evolve during a CPMG relaxation element. By fitting single, double, and triple quantum datasets, akin to recording the single quantum dataset at static magnetic fields of Bo, 2Bo and 3Bo, we show that accurate exchange values can be obtained even in cases where exchange rates exceed 10,000 s-1. The utility of the double quantum experiment is demonstrated with a pair of cavity mutants of T4 lysozyme (T4L) with ground and excited states interchanged and with exchange rates differing by fourfold (~ 900 s-1 and ~ 3600 s-1), as well as with a fast-folding domain where the unfolded state lifetime is ~ 80 µs.

Measuring the signs of the methyl 1H chemical shift differences between major and 'invisible' minor protein conformational states using methyl 1H multi-quantum spectroscopy.

Carr-Purcell-Meiboom-Gill (CPMG) type relaxation dispersion experiments are now routinely used to characterise protein conformational dynamics that occurs on the µs to millisecond (ms) timescale between a visible major state and 'invisible' minor states. The exchange rate(s) ([Formula: see text]), population(s) of the minor state(s) and the absolute value of the chemical shift difference [Formula: see text] (ppm) between different exchanging states can be extracted from the CPMG data. However the sign of [Formula: see text] that is required to reconstruct the spectrum of the 'invisible' minor state(s) cannot be obtained from CPMG data alone. Building upon the recently developed triple quantum (TQ) methyl [Formula: see text] CPMG experiment (Yuwen in Angew Chem 55:11490-11494, 2016) we have developed pulse sequences that use carbon detection to generate and evolve single quantum (SQ), double quantum (DQ) and TQ coherences from methyl protons in the indirect dimension to measure the chemical exchange-induced shifts of the SQ, DQ and TQ coherences from which the sign of [Formula: see text] is readily obtained for two state exchange. Further a combined analysis of the CPMG data and the difference in exchange induced shifts between the SQ and DQ resonances and between the SQ and TQ resonances improves the estimates of exchange parameters like the population of the minor state. We demonstrate the use of these experiments on two proteins undergoing exchange: (1) the ~ 18 kDa cavity mutant of T4 Lysozyme ([Formula: see text]) and (2) the [Formula: see text] kDa Peripheral Sub-unit Binding Domain (PSBD) from the acetyl transferase of Bacillus stearothermophilus ([Formula: see text]).

CPMG Experiments for Protein Minor Conformer Structure Determination.

CPMG relaxation dispersion NMR experiments have emerged as a powerful method to characterize protein minor states that are in exchange with a visible dominant conformation, and have lifetimes between ~0.5 and 5 milliseconds (ms) and populations greater than 0.5%. The structure of the minor state can, in favorable cases, be determined from the parameters provided by the CPMG relaxation dispersion experiments. Here, we go through the intricacies of setting up these powerful CPMG experiments.

Antibacterial activity of cinnamaldehyde and clove oil: effect on selected foodborne pathogens in model food systems and watermelon juice.

Natural additives for the control of microbial growth are in demand because consumers prefer them over synthetic ones. In the present investigation, the antibacterial activity of two natural preservatives, cinnamaldeyde and clove oil alone or in combinations was studied, and their potential as food preservative in model food systems and watermelon juice was evaluated. The cinnamaldehyde and clove essential oil showed minimum inhibitory concentration (MIC) at or below 5000 mg/l, and fractional inhibitory studies using both the oils showed synergistic effect. In artificially inoculated barley model food system and cabbage model food system, 2 MIC of oils was able to reduce the growth of the tested bacteria (more than 5 log) during 4 weeks storage at 37 °C, and similar reduction was also observed when combinations of oils were used at one eighth of MIC against Bacillus cereus and Yersinia enterocolitica, and one fourth of MIC against Staphylococcus aureus and Escherichia coli. Natural contaminants of watermelon juice were also reduced by the combination of one fourth of MIC of the oils, which was more effective than individual 2 MICs. These findings may be useful for food applications, but their effect on sensory quality of various foods need to be studied.

Anatomical variants of surgically important landmarks in the sphenoid sinus: a radiologic study in Southeast Asian patients.

PURPOSE: Failure of a surgeon to understand the local variations of the anatomical landmarks of the sphenoid sinus is a potential risk factor to cause damage to the optic nerve (ON) or internal carotid artery (ICA) that lies on the walls of the sphenoid sinus. The aim of this study was to identify the anatomical variants of the sphenoid sinus and its related surrounding structures among the Southeast Asian (SEA) population, based on computed tomography (CT) scans. MATERIALS AND METHODOLOGY: This cross-sectional study analyzed 300 CT scans of the brain, paranasal sinuses (PNS), and head and neck (H&N) at a tertiary referral centre in Malaysia utilizing the Osirix software. The images were reconstructed into 1 mm cuts on bone window. Demographic details and scan findings were documented in a standardized data collection sheet. RESULTS: The rates of ON dehiscence, ICA dehiscence and ICA protrusion in the SEA population were 7.0, 3.0 and 10.0 %, respectively. The rate of ON protrusion was 2.3 %. There was no statistically significant relationship (p > 0.05) noted on Chi-square test, between anterior clinoid process (ACP) pneumatization and ON protrusion. The rate of Onodi cells in our population was 14.3 %. The average vertical distance of the ostia from the roof of the posterior choanae was 1.42 cm (±0.32). The horizontal distance of the ostia from the anterior end of the superior turbinate was 1.58 cm (±0.41) and the oblique distance of the ostia from the anterior nasal spine was 5.35 cm (±0.48). Independent t tests showed that there is a statistically significant difference between the means of each of these parameters (p < 0.001) and their international averages. CONCLUSION: The rate of ON protrusion is lower in the SEA population, whereas the rates of ON dehiscence, ICA dehiscence and ICA protrusion fall within the range of international averages. In our population, ACP pneumatization is not related to ON protrusion. The distance of the ostia from given landmarks was significantly shorter than in other studies.

Anatomical variations of the sphenoid sinus and its adjacent structures: a review of existing literature.

The sphenoid sinus, one of the posterior groups of sinuses, has long been regarded as a 'neglected sinus' due to the anatomical location, poor understanding and poor accessibility, till the advent of endoscopes and modern imaging techniques. Increasing knowledge and greater understanding of this sinus has permitted an evolution in surgical practices and boundaries. Various literatures of the past report a great variety of rates of pneumatization, rates of optic nerve protrusion and dehiscence, as well as internal carotid artery (ICA) protrusion and dehiscence. One similarity noted among these studies is that the rates vary according to the ethnicity of the patients. Recommendations have also been made along the way with regard to modified surgical techniques. This review aims to describe the pneumatization of sphenoid sinus and the topographical relation of the optic nerve and ICA in different populations.

A case series of Nasopharyngeal Carcinoma among Indians, a low risk population, in Perak State, Malaysia.

Nasopharyngeal carcinoma (NPC) is rare among people of Indian ethnicity. A short retrospective case review of clinical records of Indian patients diagnosed with nasopharyngeal carcinoma in a period of 5 years was conducted. Their slides were further subjected to EBV encoded RNA (EBER) - In- situ Hybridization (ISH). The histologic subtype was nonkeratinizing carcinoma in all 4 patients. All were Epstein Barr Virus (EBV) positive. We believe that the crucial factor responsible for nasopharyngeal carcinoma is genetics; either a genetic susceptibility among high risk groups or genetic resistance/immunity in low risk groups. Further genetic studies are required to look for somatic or inherited chromosomal mutations among the various risk populations.