Mean Ocular Perfusion Pressure Effect During Pars Plana Vitrectomy on the Foveal Avascular Zone: A Pilot Study.

Purpose: To evaluate the effect of mean ocular perfusion pressure on the foveal avascular zone (FAZ) area in eyes with successful retinal detachment (RD) surgery. Methods: This prospective pilot fellow eye-controlled study measured the intraoperative mean ocular perfusion pressure in eyes having surgery for rhegmatogenous RD (RRD). Postoperatively, the FAZ area was measured; the change was calculated as the difference in the FAZ area between the operated eye and the contralateral control eye. Results: The study comprised 8 patients with a mean age (±SD) of 53.38 ± 13.92 years. The mean superficial FAZ area was not different between operated eyes and control eyes, while the deep FAZ area was significantly larger in operated eyes. There was a strong negative correlation between the mean ocular perfusion pressure and the change in the deep FAZ area (Spearman ρ, -0.73; P = .04); the correlation between the mean ocular perfusion pressure and the change in the superficial FAZ area was not significant (Spearman ρ, -0.24; P = .57). A significant linear regression was found between the mean ocular perfusion pressure and the change in the deep FAZ area (R2 = 0.388). The predicted enlargement of the deep FAZ area was 0.03 mm with every 1 mm Hg decrease in the mean ocular perfusion pressure. Conclusions: Lower intraoperative mean ocular perfusion pressure is associated with enlargement of the deep FAZ area in eyes having successful RRD surgery.

Outcomes of Haematopoietic Stem Cell Transplantation in Beta Thalassemia Major with Fully Matched Parents as Donor.

OBJECTIVE: To determine the outcome of beta thalassemia major (BTM) patients undergoing haematopoietic stem cells (HSCT), with fully matched parents as donors vs. matched sibling donors (MSD). STUDY DESIGN: Observational Study. Place and Duration of the Study: Department of Clinical Haematology and Bone Marrow Transplantation Centre, Rawalpindi, Pakistan, from January 2013 to July 2023. METHODOLOGY: Group A consisted of BTM patients who underwent HSCT with fully matched siblings as donors, and Group B consisted of BTM patients who underwent HSCT with fully matched parents as donors. Study data included the age and gender of both recipients and donors, source and dose of stem cells infused, and stage and grades of acute and chronic graft versus host disease (GvHD). All patients received Myeloablative conditioning regimen (MAC). Data were collected to assess patients' demographics, response to HSCT, remission rate, disease free survival (DFS), relapse, and GvHD free survival (GRFS), and overall survival (OS). RESULTS: The mean age of the 54 patients was 5.90 ± 3.29 years. The mean TNC and CD34 doses were 4.99 + 1.13 and 5.42 + 3.70, respectively. Mean time for neutrophil engraftment in both groups was 14.88 + 4.51 days and platelets engraftment was 23.0 + 5.35 days. Most common cause of death was neutropenic sepsis followed by aGVHD. Seven patients had graft rejection. There was no significant association found between graft rejection with donor relation though graft rejection was higher in OS in this study was 70.4%. OS was equal in both groups. Disease free survival was superior in MSD (63%) than parent group (57.7%). CONCLUSION: Allogenic bone marrow transplantation with parents as donors in BTM patients yields outcomes comparable to those with matched sibling donors. This finding is especially relevant in regions like Pakistan, where donor registries and high-resolution HLA typing may be limited. KEY WORDS: Beta thalassemia major, Haematopoietic stem cell transplant, Post-transplant outcome.

Design, synthesis, and biological evaluation of HDAC6 inhibitors targeting L1 loop and serine 531 residue.

Histone deacetylases (HDACs) are a group of enzymes that remove acetyl groups from histones, leading to the silencing of genes. Targeting specific isoforms of HDACs has emerged as a promising approach for cancer therapy, as it can overcome drawbacks associated with pan-HDAC inhibitors. HDAC6 is a unique HDAC isoform that deacetylates non-histone proteins and is primarily located in the cytoplasm. It also has two catalytic domains and a zinc-finger ubiquitin binding domain (Zf-UBD) unlike other HDACs. HDAC6 plays a critical role in various cellular processes, including cell motility, protein degradation, cell proliferation, and transcription. Hence, the deregulation of HDAC6 is associated with various malignancies. In this study, we report the design and synthesis of a series of HDAC6 inhibitors. We evaluated the synthesized compounds by HDAC enzyme assay and identified that compound 8g exhibited an IC50 value of 21 nM and 40-fold selective activity towards HDAC6. We also assessed the effect of compound 8g on various cell lines and determined its ability to increase protein acetylation levels by Western blotting. Furthermore, the increased acetylation of α-tubulin resulted in microtubule polymerization and changes in cell morphology. Our molecular docking study supported these findings by demonstrating that compound 8g binds well to the catalytic pocket via L1 loop of HDAC6 enzyme. Altogether, compound 8g represents a preferential HDAC6 inhibitor that could serve as a lead for the development of more potent and specific inhibitors.

Exploring new histone deacetylase 6 inhibitors and their effects on reversing the α-tubulin deacetylation and cell morphology changes caused by methamphetamine.

Indazole-based HDAC6 inhibitors with novel zinc-binding modifications were synthesized and evaluated to determine their potential to inhibit HDAC6. The analogs were subjected to a histone deacetylase (HDAC) enzyme assay, which led to identification of compounds 3a and 3b. Both compounds demonstrated higher potency and selectivity as HDAC6 inhibitors with IC50 values of 9.1 nM and 9.0 nM, respectively, and highlighted the importance of the hydroxamic acid moiety for binding to Zn2+ inside the catalytic pocket of HDAC enzymes. In the neuroblastoma SH-SY5Y cell line, both compounds efficiently acetylated α-tubulin but not histone H3 at a low concentration of 0.5 µM. Moreover, compounds 3a and 3b effectively reversed the deacetylation of α-tubulin caused by methamphetamine in the SH-SY5Y cell line, suggesting the potential usefulness of HDAC6 selective inhibition in restoring blood brain barrier integrity by reversing methamphetamine-induced deacetylation.

SPC-180002, a SIRT1/3 dual inhibitor, impairs mitochondrial function and redox homeostasis and represents an antitumor activity.

Since sirtuins (SIRTs) are closely associated with reactive oxygen species (ROS) and antioxidant system, the development of their selective inhibitors is drawing attention for understanding of cellular redox homeostasis. Here, we describe the pharmacological properties of SPC-180002, which incorporates a methyl methacrylate group as a key pharmacophore, along with its comprehensive molecular mechanism as a novel dual inhibitor of SIRT1/3. The dual inhibition of SIRT1/3 by SPC-180002 disturbs redox homeostasis via ROS generation, which leads to an increase in both p21 protein stability and mitochondrial dysfunction. Increased p21 interacts with and inhibits CDK, thereby interfering with cell cycle progression. SPC-180002 leads to mitochondrial dysfunction by inhibiting mitophagy, which is accompanied by a reduction in oxygen consumption rate. Consequently, SPC-180002 strongly suppresses the proliferation of cancer cells and exerts anticancer effect in vivo. Taken together, the novel SIRT1/3 dual inhibitor, SPC-180002, impairs mitochondrial function and redox homeostasis, thereby strongly inhibiting cell cycle progression and cancer cell growth.

Myopia Progression in Adults: A Retrospective Analysis.

SIGNIFICANCE: Studies on adult myopia progression are limited. This retrospective analysis of a large data set of young adult myopes characterizes myopia progression during adulthood. PURPOSE: This study aimed to determine the mean annual progression of myopia and to estimate the proportion of progressors in adult myopes. METHODS: Longitudinal, noncycloplegic subjective refraction data for young adult myopes (spherical equivalent refractive error, -0.5 D or more), age ranging from 18 to 30 years, were retrospectively analyzed. The mean annual progression, as well as the proportion of progressors (at least -0.50 D shift between visits and annualized progression of -0.25 D or more), was estimated. RESULTS: A total of 354 myopes (230 females [64.7%]), with a mean (standard deviation) age of 22.2 (3.8) years, were considered. The mean (standard deviation) annualized progression was -0.10 (0.21), -0.08 (0.2), and -0.04 (0.21) D in the 18- to 21-year, 22- to 26-year, and 27- to 30-year age groups, respectively ( P = .003). The difference between 18- to 21- and 27- to 30-year age groups was significant ( P = .05), whereas all other pairwise comparisons were not significant. The proportion (95% confidence interval) of progressors in the 18- to 21-, >21- to 26-, and >26- to 30-year age groups was 18.3% (14.9 to 21.7%), 10.9% (7.1 to 14.7%), and 8.8% (4.4 to 13.1%), respectively. The proportion of progressors working or studying in a higher learning/academic environment was 16.2% with an odds ratio (95% confidence interval) for progression of 2.07 (1.15 to 3.74) compared with those in nonacademic environments ( P = .02), with no significant effect of sex or ethnicity. CONCLUSIONS: This study is consistent with other studies on myopia in young adults, which show that myopia does not progress by substantial amounts throughout the adult years, particularly after the age of 21 years. Although future studies may be challenged by the small rates of change and the small proportion of progressors, further research is needed to understand the implications of adult myopia progression on clinical management.

Suprachoroidal silicone oil migration following 27 gauge 3 ports pars plana vitrectomy - a rare complication and its management.

Suprachoroidal silicone oil migration is an unusual complication of small gauge 3 ports Pars plana vitrectomy (3PPV) system. Our objective is to report a retrospective, observational case of an intra-operative suprachoroidal silicone oil (SO) migration during 27 gauge 3PPV and its successful surgical management. A 49 years old male patient with type 2 diabetes, presented to the ophthalmology outpatient department with reduced visual acuity in his right eye. He was diagnosed as having tractional retinal detachment involving macula. During combined phaco-vitrectomy following injection of SO, peripheral choroidal elevations were noted suggesting suprachoroidal SO migration. In an attempt to drain this intra-operatively nasal sclerotomy was enlarged. Post-operative B scan showed significant choroidal detachment for which patient was re-scheduled for surgery after 1 day. Three radial trans-scleral incisions (2 nasal and 1 temporal) for drainage were made at the site of maximum choroidal detachment. By massaging and widening these scleral incisions, suprachoroidal haemorrhage and SO was successfully drained with good post-operative visual improvement.

Dataset of usage pattern and energy analysis of an Internet of Things-enabled ceiling fan.

Many electrical appliances have progressed from sheer prototypes to viable products by being automated with the help of sensors and Internet of Things (IoT). In this data driven century, there aren't many data-centric solutions for the effective use of residential and commercial ceiling fans. For the said reason, sensors were installed on a remote-controlled BLDC ceiling fan, and a large amount of user data with environmental indicators such as temperature and humidity, was collected. This data along with the fan speed was logged to a cloud server over Wi-Fi using a Wi-Fi enabled microcontroller. The raw data consists of timestamp, temperature, humidity, and fan speed. The data is logged depending on the change of any parameter rather than a specific interval. The logged data is then visualized on the cloud server to monitor the usage patterns of the appliance and its subsequent energy consumption. The dataset is comprised of the fan data from the bedroom, living room, and lounge obtained by the resident's consent. This data is useful for data scientists, environmentalists, fan manufacturers, architects, social scientists, and several other field enthusiasts. The data can be analyzed based on monthly average temperature and humidity energy consumed, operational time per day or month and monthly/weekly summary of usage. Furthermore, by applying Artificial Intelligence (AI) algorithms on such data, it is feasible to extract patterns that indicate the appliance usage and identify changes in the daily routine. Many machine learning techniques can be applied on the dataset to introduce intelligent control of the appliance for adaptable operation without compromising on the comfort level of the user.

An unusual presentation of type III late onset multiple-acyl-CoA dehydrogenase deficiency leading to a review of its classification system.

Multiple-acyl-CoA dehydrogenase deficiency (MADD) is a rare autosomal recessive disorder which can be split into three types. Type III MADD is associated with acute or subacute proximal muscle weakness and other variable non-specific features making it a challenging diagnosis for the clinician. This case report describes MADD in a 64 year-old lady, thought to be one of the latest first presentations of the disease. Unusually for this condition, the initial presentation was with dyspnoea. Furthermore, since this case provides further evidence that gene variants can predict age of onset, we advocate for further subclassification of type III MADD into late onset MADD (LO-MADD) when homozygous gene variants are present and very LO-MADD when heterozygous gene variants are found.

Surgical safety checklist compliance: The clinical audit.

Introduction: The surgical safety checklist consists of three components: sign-in, performed before the induction of anesthesia; time-out, performed before skin incision; and sign-out, performed immediately after skin closure or before the patient leaves the operating theatre. This study aims to assess compliance with the World Health Organization (WHO) Surgical Safety Checklist (SSC) and explore the barriers facing in properly implementing the surgical safety checklist in operation theatres of a tertiary care hospital. Methodology: The observational clinical audit was conducted in Surgical Unit I, Benazir Bhutto Hospital, Rawalpindi, Pakistan. Compliance with the surgical safety checklist was observed before and after the educational intervention. After completion of the clinical audit operating theatre staff was asked about the barriers to compliance with the surgical safety checklist using an interview sheet. Mean, and standard deviation was calculated for quantitative variables, whereas frequencies and percentages were calculated for categorical variables using SPSS version 25.0. Results: Compliance with all the steps of the surgical safety checklist was improved after an educational intervention, with the highest improvement in compliance (66.7%) observed with the Sign-out step "Count of sponges and needles & instruments complete?" Moreover, filling of the patient board and documentation of procedure in the patient file were also improved. Lack of awareness and training to follow the surgical safety checklist was the commonest barrier to compliance with the surgical safety checklist. Conclusion: Implementing the surgical safety checklist will not only upgrade the patient safety measures but also integrate teamwork skills and improve the local departmental culture.

The Severity of Depression, Anxiety, and Stress: Recommendations From Joint Work of Research Center and Psychology Clinics in COVID-19 Pandemic.

The COVID-19 pandemic has significantly affected the psychological stability of general population of Pakistan. However, research on the severity of COVID-19 induced depression, anxiety, and stress (DAS) in Pakistan is scarce. This paper thereby investigates the severity of COVID-19 induced DAS based on demographic, socioeconomic, and personal feeling variables by modeling DAS. Snowball sampling strategy was adopted to conduct online survey from July 03, 2021 to July 09, 2021. Out of 2,442, 2,069 responses from Karachi were included. Descriptive and inferential statistics (binary and multinomial logistic regression analysis) were performed using SPSS V21 (IBM, 2013) to identify significant determinants and their association with DAS severity. The result of this study indicates 27.8, 21.7, and 18.3% respondents suffer from severe and extremely severe states of depression, anxiety, and stress, respectively. Binary logistic regression revealed that age is a significant determinant with odds of having 4.72 (95% CI = 1.86-11.97) and 5.86 (95% CI = 2.26-15.2) times greater depression, and stress for respondents aged 19-26 years. Moreover, gender-based difference is also observed with females 1.34 (95% CI = 1.08-1.68) and 1.75 (95% CI = 1.40-2.20) times more likely to exhibit anxiety and stress than males. Furthermore, marital status is a significant determinant of depression with odds of having depression is 0.67 (95% CI = 0.48-0.93) times greater for married population. Multinomial logistic regression revealed that those who believe COVID-19 pandemic has affected them mentally, fear new COVID-19 cases and deaths, depressed due to imposition of lockdown, believe they will not survive COVID-19 infection, and spend more time on social media gathering COVID-19 updates suffer from extremely severe state of depression (OR mental-effect-of-pandemic = 3.70, OR new-COVID-19-cases-and-deaths = 2.20, OR imposition-of-lockdown = 17.77, OR survival-probability = 8.17, OR time-on-social-media = 9.01), anxiety (OR mental-effect-of-pandemic = 4.78, OR new-COVID-19-cases-and-deaths = 3.52, OR imposition-of-lockdown = 5.06, OR survival-probability = 8.86, OR time-on-social-media = 5.12) and stress (OR mental-effect-of-pandemic = 6.07, OR imposition-of-lockdown = 11.38, OR survival-probability = 15.66, OR time-on-social-media = 4.39). Information regarding DAS severity will serve as a platform for research centers and psychological clinics, to work collectively and provide technology-based treatment to reduce the burden on the limited number of psychologist and psychotherapist.

Design, synthesis, and biological evaluation of histone deacetylase inhibitor with novel salicylamide zinc binding group.

INTRODUCTION: Histone deacetylases (HDACs) have emerged as important therapeutic targets for various diseases, such as cancer and neurological disorders. Although a majority of HDAC inhibitors use hydroxamic acids as zinc binding groups, hydroxamic acid zinc-binding groups suffer from poor bioavailability and nonspecific metal-binding properties, necessitating a new zinc-binding group. Salicylic acid and its derivatives, well-known for their therapeutic value, have also been reported to chelate zinc ions in a bidentate fashion. This drew our attention towards replacing hydroxamic acid with salicylamide as a zinc-binding group. METHODS: In this study, for the first time, compound 5 possessing a novel salicylamide zinc-binding group was synthesized and evaluated biologically for its ability to inhibit various HDAC isoforms and induce acetylation upon α-tubulin and histone H3 among MDA-MB-231 cells. RESULTS: Compound 5 exhibits selective inhibition against class I HDAC isoforms (HDAC1, 2, and 3) over class II and IV HDAC isoforms (HDAC4, 6, and 11). The exposure of MDA-MB-231 cells to compound 5 efficiently induced the acetylation of more histone H3 than α-tubulin, suggesting that compound 5 is a class I selective HDAC inhibitor. Moreover, the molecular docking study indicated that the salicylamide zinc-binding group of compound 5 coordinates the active zinc ion of class I HDAC2 in a bidentate fashion. CONCLUSION: Overall, salicylamide represents a novel zinc-binding group for the development of class I selective HDAC inhibitors. GRAPHICAL ABSTRACT: (http://links.lww.com/MD/G668).

Comprehensive overview of IRVAN syndrome: a structured review of Case Reports and Case Series.

Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome is a rare spectrum of retinal vasculitis, aneurysms, and neuroretinitis affecting young individuals in their third decade. Most of our current knowledge is based on case reports, case series, and a handful of collaborative studies. There is much diversity in treatment approaches and outcomes in the reported literature. We have aggregated published case reports and case series into quantitative and narrative synthesis to draw evidence-based conclusions toward clinical features, atypical and rare findings, systemic associations, disease course, and treatment outcomes. The analysis suggested the disease mostly affects young individuals with a female predilection. Anterior chamber and vitreous inflammation are common than previously believed. The most prevalent pattern of retinal vasculitis in IRVAN eyes is mixed vasculitis, followed by arteritis and phlebitis. Most eyes at the time of presentation have capillary nonperfusion and require treatment. Most eyes retain good visual acuity; however, treatment is required to maintain visual function. Intravitreal antivascular endothelial growth factors administered as an adjunct to retinal laser photocoagulation are more likely to improve visual outcomes. Besides, we have discussed the different hypotheses on the etiopathogenesis of the disease and stronger evidence suggests an inflammatory origin of the disease.

Eyelid Myokymia-a Presumed Manifestation of Coronavirus Disease 2019 (COVID-19).

The purpose of this study is to report eyelid myokymia in patients recently recovered from COVID-19 disease. A cohort of 15 patients who developed eyelid myokymia during or immediate post-recovery of systemic disease were evaluated. Demographic, clinical characteristics, effect of age, and hospitalization on the disease course were studied. The disease course was evaluated every month for 3 months period. All, except 2, patients had complete resolution of lid myokymia within 3 months of onset. Median [IQR] myokymia recovery time was 42 [31,60] days. Age and duration of hospitalization had a significant linear relationship with myokymia recovery time. Recovery was delayed by 2.64 days with every 1-year increment in age and by 6.19 days with every additional day of hospital stay. Recovery time was independent of severity of systemic disease (P = .055) and gender (P = 0.2). Eyelid myokymia can be a possible manifestation of COVID-19 recovery phase. While myokymia recovers gradually in all these patients, older age and a longer duration of hospitalization are associated with slower recovery.

A Novel Method of Quantifying the Choriocapillaris in Normal and Post-inflammatory Eyes.

OBJECTIVE: To assess the reliability and validity of gray level co-occurrence matrices (GLCM) in the quantification of choriocapillaris and describe GLCM features in normal and eyes with resolved acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and serpiginous choroiditis (SC). METHODS: In this, multicenter, reliability, validity and comparative study; OCTA was performed on eyes with resolved APMPPE and SC and normal individuals. CC texture classification, low flow area measurements and GLCM feature extraction were performed. RESULTS: A total of 13 normal, 8 APMPPE and 15 SC eyes were analyzed. All GLCM parameters demonstrated an excellent reliability. GLCM parameters were differently distributed across the three groups. Decision-tree based on the random forest predictive model provided an overall accuracy of 86% in classifying the three groups using GLCM features. CONCLUSION: These data demonstrated an excellent reliability and validity of GLCM features in quantifying the choriocapillaris in healthy and diseased eyes.

Teaching the Teacher: Assessing Barriers to Identity Formation of Clinical Teachers in a Developing Country.

PHENOMENON: Clinical teachers' identity formation is understudied in developing countries like Pakistan. Despite producing thousands of international medical graduates per year, Pakistani medical education is still in its infancy. The application of Western medical education methods and theories is beset by unique socio-cultural challenges. These must be identified and addressed to ease our physicians' transition from clinician to teacher and maximize their teaching output in a resource-limited setting. APPROACH: Eight clinical teachers were interviewed from Combined Military Hospital Kharian, Punjab, Pakistan in July 2020. Semi-structured questionnaires were used, and interviews were audio-taped to generate transcripts. These were analyzed qualitatively and coded, developing themes regarding barriers to identity formation. FINDINGS: Six themes reflected possible barriers to identity formation and fell under two domains: individual and systemic issues. At the individual level these themes were: conflicting priorities, lack of autonomy, and language barriers. Systemic issues were found to be: disconnect between educationists and teachers, the absence of incentives, and lack of institutional support. INSIGHT: Identifying barriers to identity formation can aid clinical teachers' development and encourage discourse around providing increased institutional support to teachers to overcome said barriers. Both the individual and the institute are stakeholders in the process of identity formation and dialogue between the two can lead to improved teaching outcomes.

Impending disaster: rise of the epsilon variant in Pakistan and the way forward.

The constantly mutating severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) does not appear to be slowing down any time soon. All countries, particularly developing countries, must adapt and strategically plan their way of life around the pandemic, while doing everything possible to keep the mortality rate and spread of the newly emerging variants as low as possible, in order to avoid a further blow to the economy and way of life. Pakistan is one such developing country that is currently battling the dangerous delta strain of SARS-COV-2 with limited resources and has recently seen the emergence of an equally transmissible and highly infectious epsilon strain. This is a concerning situation considering that Pakistan's already overburdened health system and faltering economy cannot withstand another dangerous SARS-COV-2 variant attack. This article highlights some strategies for the country to fortify its defences to prevent the epsilon variant from spreading before it is too late, and emphasises that while identifying potential immune evasion mechanisms in SARS-COV-2 variants is critical in the fight against COVID-19, it is also critical to develop methods of efficient and cost-effective detection to identify an early outbreak and then vigilantly and systematically plan area lockdowns before any hope of conquering this pandemic is lost.

Attitudes and practice of surgeons in reporting medical errors at a tertiary care hospital.

Medical error reporting is essential in creating a culture of accountability in our healthcare system. The aim of this study was to evaluate the frequency of reporting errors by surgeons in our setup and to analyse the factors resulting in under-reporting of medical errors. A total of 96 practicing surgeons at Mayo Hospital, Lahore were surveyed between the months of February, 2018 to June 2018 on their beliefs regarding the reporting of medical errors by means of a specifically designed questionnaire. This study revealed that 71 (74%) respondents had committed a medical error but only 16 (16.6%) of them reported those errors. Major factors in under-reporting of errors included work stress and fear of medico-legal consequences due to disclosure of error. Eighty-four (87.5%) believed that increase in reporting medical errors would contribute to a better system. Most surgeons had a positive view towards the process but believed that the reporting system was ineffective.

Distinguishing Voluntarily Upregulation of Localized Central Alpha from Widespread Posterior Alpha.

Neurofeedback (NF) training based on alpha upregulation has been widely used on patient and healthy populations. However, active voluntary modulation of central or widespread posterior alpha in response to central alpha feedback is still ambiguous. The objective of this study is to confirm whether patients learn to truly increase alpha power and to determine if patients modulate central or widespread alpha power when alpha feedback is provided from central brain region. This EEG-based NF study was conducted on seven paraplegic patients with same injury type, pain location, and sensitization to ensure homogeneity. In addition to routine NF training sessions, various experiments were performed to compare alpha NF modulation received from C4 with alpha shift during cognitive tasks, occipital or parieto-occipital cortex, and Laplacian montage which is expected to separate localized alpha from widespread alpha, to attain objectives. Moreover, imaginary coherence analysis in alpha band was also performed to check whether C4 training site is coupled with other brain regions and to confirm whether activity at training site leads/lags the activity of other brain regions. The results indicate widespread alpha modulation in patients during regular NF sessions (p < 0.05) with large effect size (> 0.8), sufficiently high statistical power (> 80%), and a narrower confidence interval (CI) in response to NF provided from the central brain region reflecting less uncertainty and higher precision. However, small effect size obtained with Laplacian montage require patients to be trained with Laplacian feedback to achieve a reliable conclusion regarding localized alpha modulation. The outcomes of this study are not only limited to validate true alpha modulation in response to central alpha feedback but also to explore the mechanism of central alpha NF training.