REGULATORY PERSPECTIVE FOR GENE THERAPY PRODUCTS IN THE USA, EU AND JAPAN AND FUTURE ASPECTS

Gene Therapy Products (GTPs) hold immense promise in revolutionizing medical treatments by altering genetic expressions to address various diseases. This study gives a summary of gene therapy products and their prospective uses, their historical development and several treatment options, as an in-depth exploration of the regulatory considerations for GTPs in the United States of America (USA), European Union (EU), and Japan, along with insights into future aspects of this field. A comprehensive discussion follows detailing the regulatory landscape and approval pathways in the USA, EU, and Japan. Programs that are exclusive to each area, such as PRIME (Priority Medicines) in the EU, USA's RMAT (Regenerative Medicines Advanced Therapy) designation and the Sakigake system in Japan are examined. Milestone meetings, approval requirements, and specific regulatory guidelines for GTPs in each region are also thoroughly covered. A list of approved GTPs and a glimpse into the future of the field. Anticipated trends include increasing investments, challenges related to production costs, expansion of manufacturing capabilities, and regulatory updates. The various regulatory strategies in each area and their efforts to balance patient access and safety will have a big impact on GTPs marketed in the future. Japan is well-positioned to maintain it’s as a global leader in regenerative medicine and cell treatments because of its favourable regulatory environment and government backing.

REGULATORY CHALLENGES AND LANDSCAPES OF MONOCLONAL ANTIBODY REGISTRATION: GLOBAL OUTLOOK

Objective: This review aims to illuminate the unprecedented growth and versatile therapeutic landscape of monoclonal antibody (mAb) products, highlighting their significant impact on diverse medical fields such as oncology, septicemia treatment, infection management, and substance abuse disorder interventions. This review outlines the challenges associated with the development, manufacturing, and regulatory approval of monoclonal antibodies, emphasizing the need for diligent attention to overcome these complexities. The review comprehensively examines the historical evolution and therapeutic applications of monoclonal antibodies, emphasizing their potent and versatile characteristics that have enabled successful interventions in challenging regulatory approvals. It delves into the critical considerations in manufacturing, regulatory navigation, and the strategic integration of expedited approval pathways, providing a holistic understanding of the intricate terrain of innovation, clinical translation, and impactful patient care in the realm of monoclonal antibody products. Monoclonal antibodies have significantly advanced medical treatment in various domains, revolutionizing cancer therapy, offering new avenues for septicemia management, augmenting the arsenal against infections, and opening novel pathways for addressing substance abuse disorders. Their development and regulatory approval are associated with challenges of scientific innovation, manufacturing, and regulatory compliance. Despite the challenges, monoclonal antibodies have demonstrated remarkable potential in addressing complex medical conditions. The review serves as a compass, guiding researchers, clinicians, and regulatory authorities through the intricate terrain of monoclonal antibody innovation and clinical translation. It emphasizes the need for diligent attention to overcome the complexities associated with their development and regulatory approval while highlighting their significant impact on advancing patient care.

ENHANCING OTC MONOGRAPH DRUG REGULATION THROUGH USER FEE PROGRAM

Food and Drug Administration (FDA) has introduced a distinctive regulatory program known as Over-the-Counter Monograph Drug User Fee Program (OMUFA) to improve the efficacy and security of over-the-counter (OTC) medications made available to consumers. The program, which represents a pivotal shift in the regulatory landscape, aims to address the challenges associated with the oversight of OTC monograph drugs. The OMUFA's primary objective is to expedite the review and approval process of OTC monograph drugs while maintaining stringent safety standards. By imposing user fees on manufacturers and sponsors seeking to bring new OTC products to market or seeking updates for existing ones, the program is designed to support the FDA's ability to allocate additional resources for timely reviews and assessments. This work delves into the key components and mechanics of the OMUFA, such as the user fee structure, types of submissions covered, and the corresponding performance goals established for the FDA. While acknowledging the benefits of the OMUFA, this work also discusses potential challenges and concerns raised by industry stakeholders and consumer advocacy groups. This critical regulatory initiative has the potential to facilitate further research and discussions on optimizing drug safety and access within the OTC market through required modifications and initiatives.

Clinical characteristics and colposcopy appearance of cervical intraepithelial neoplasia

Background: Cervical cancer ranks as the second most prevalent cancer among women globally, particularly affecting those in economically disadvantaged regions. This study aimed to explore the epidemiology and clinical characteristics of cervical intraepithelial neoplasia (CIN).Methods: The cross-sectional study was conducted at the Colposcopy Center, Comilla Medical College Hospital, spanning from July 2015 to December 2015. Face-to-face interviews using a preformed questionnaire were employed for data collection. Inclusive criteria were followed for the enrolment of 200 participants, and a simple random sampling technique was utilized. Statistical analysis was planned in the SPSS program. Ethical clearance was obtained from the Comilla Medical College Hospital Ethical Review Committee to ensure confidentiality.Results: Among the 200 women studied, 15% were aged 20-29, 42% were 30-39, 38% were 40-49, and 5% were >50 years old. Illiteracy was prevalent in 30%, with 50% having primary education. CIN incidence was higher among illiterates and those in poor socioeconomic status (55.56%). Early sexual exposure, longer duration of exposure, and higher parity correlated with increased CIN risk. Non-use of contraception was observed in 30% of women, with 44.44% exhibiting CIN. Clinical features included predominant complaints of P/V discharge and various bleeding patterns.Conclusions: CIN prevalence was higher among 30-39-year-olds, emphasizing the impact of illiteracy, low socioeconomic status, early marriage, prolonged marital duration, high parity, and limited contraception use. Clinical manifestations primarily comprised P/V discharge and diverse bleeding patterns. This study underscores the need for targeted interventions addressing socio-demographic risk factors for effective cervical cancer prevention.

STABILITY INDICATING UPLC METHOD FOR ESTIMATION OF BENAZEPRIL AND HYDROCHLOROTHIAZIDE IN BULK AND COMBINED DOSAGE FORM

Objective: The main objective was to develop stability indicating UPLC technique for simultaneous estimation of Benazepril and Hydrochlorothiazide in bulk and formulation.Methods: 0.1% Triethylamine phosphate: Methanol (25:75v/v) was used as the mobile phase. Benazepril linearity was found to be 4-20 µg/ml and Hydrochlorothiazide linearity was found to be 5-25 g/ml. The detection wavelength was 236 nm, and the retention period of Benazepril was 3.4 min and Hydrochlorothiazide was 5.4 min with a flow rate of 1.0 ml/min. According to the ICH guidlines, the proposed method was validated and stress studies revealed that the drugs are prone to alkali and peroxide stress conditions.Results: The calibration curve was plotted, and the regression equations for Benazepril were y = 2,01,491.67x+60,532.30 with a correlation coefficient (r2) of 0.9997 and Hydrochlorothiazide were y = 64,635.86x-74,607.10 with a correlation coefficient (r2) of 0.9994. According to the accuracy research, the percent recovery of Benazepril is 99.09-100.69 % and that of Hydrochlorothiazide is 98.27-101.88%, both of which are within the ICH recommendations. Benazepril has a limit of detection of 0.08 g/ml-0.24 g/ml and Hydrochlorothiazide has a limit of quantitation of 0.03 g/ml-0.10 g/ml. The procedure was found to be straightforward, linear, rapid, exact, repeatable, and robust. It was determined that the % RSD was within ICH norms. Stress degradation tests showed the drug's vulnerability to oxidative, thermal, photolytic, acid, basic, and neutral hydrolysis stress conditions. Under the circumstances of alkali and peroxide stress, it was discovered that the drug degraded most quickly.Conclusion: The developed chromatographic technique under consideration was suitable for the accurate, precise, and quick simultaneous measurement of hydrochlorothiazide and benazepril in both their bulk and medicinal dose forms.

A case of partial androgen insensitivity syndrome with undescended testis and clitoromegaly

Androgen insensitivity syndrome is a rare disorder of sex development that results from genetic mutations affecting the androgen receptor. Recently, we encountered a case of a 13-year-old individual who had been raised as female and sought medical attention for primary amenorrhea, which led to the discovery of partial androgen insensitivity syndrome. Early detection and gonad removal are necessary to mitigate the risk of cancer. Additional management steps such as corrective surgery and psychological support can also be valuable.

Prevalence of Health Problems, Professional and Financial Satisfaction among Doctors Working Across Vadodara City: A Cross-sectional Study

Background: The present study was conducted to know the distribution of various health problems among doctors and to assess professional and financial satisfaction levels among doctors. Methods: A Google Form questionnaire-based cross-sectional study was conducted among 122 doctors in Vadodara selected purposively after taking consent. Google form was circulated by email and WhatsApp groups. The form consisted of questions related to demographic details, health problems, financial and job satisfaction. All the responses were recorded and analyzed in MS Excel 2019. Results: Among the 122 doctors, 89 (72.95%) were male and 33 (27.04%) were female and 101 (82.78%) doctors were taking treatment for some ailment. Around 86.9% of doctors regularly opt for a health check-up. Among the health problems reported by doctors, the most common were musculoskeletal ailments (72.13%) followed by hypertension (28.9%), diabetes (17.2), cardiac (12.3%), endocrinal (10.65%), eye (9.01), mental (6.55) problems. Approximately 37.70% of doctors answered that health problems temporarily affect their work; 5.73% of doctors felt the need to modify their work pattern. About 91.80% of doctors were satisfied by their profession, while 108 (88.52%) doctors were financially satisfied with their work. Conclusion: More than half of the professionals complained of musculoskeletal problems. The majority of health care professionals were professionally and financially satisfied.

Role of Counselling and its Impact on the Dietary Habits, Glycemic Control and Diabetic Awareness of Newly Diagnosed Type 2 Diabetes Mellitus Patients

Background : Type 2 Diabetes Mellitus is a lifestyle disorders and it leads to complications that are life threatening which can be prevented by proper Counselling and Diet monitoring of patients. Objective : To evaluate effect of Counselling on the Glycemic control, Dietary habits and Diabetes awareness of type 2 DM patients. Method : A randomized clinical trial was conducted at a tertiary hospital. 96 subjects were randomized and baseline data was gathered from all patients included in the study. Out of these 48 patients were given Counselling on various aspects of Diabetes including diet, complications, medication, lifestyle modifications, exercise etc. Lab investigations and Diet calculations were done on first and 4 months later to measure the effect of Counselling on patient抯 Diet and Glycemic control and Diabetes awareness. Results : Diabetic awareness was measured in terms of number of correct responses which increased from 325 to 542 in Intervention group and from 357 to 402 in Control group. The increase in intervention group (22.60%) was more than that of the Control group (4.59%). The amount of calories in the diet of intervention and control group was respectively 2322�1 and 2334�0. Post Intervention it was 2344�0 and 2056�7respectively. Before intervention the difference in the amount of Calories, FBS, PP2BS between the 2 groups was statistically insignificant. But after intervention the difference with reference to total calories (p=0.0003), FBS (p=0.01) and PP2BS (p=0.0001) became statistically significant. Conclusion : Counselling led to a significant improvement in the Diabetic awareness, Glycemic control and Dietary habits of patients in terms of caloric intake.

A Pilot Study Exploring Temporal Development of Gut Microbiome/ Metabolome in Breastfed Neonates during the First Week of Life / 대한소아소화기영양학회지

Purpose@#Exclusive breastfeeding promotes gut microbial compositions associated with lower rates of metabolic and autoimmune diseases. Its cessation is implicated in increased microbiome-metabolome discordance, suggesting a vulnerability to dietary changes.Formula supplementation is common within our low-income, ethnic-minority community.We studied exclusively breastfed (EBF) neonates’ early microbiome-metabolome coupling in efforts to build foundational knowledge needed to target this inequality. @*Methods@#Maternal surveys and stool samples from seven EBF neonates at first transitional stool (0–24 hours), discharge (30–48 hours), and at first appointment (days 3–5) were collected. Survey included demographics, feeding method, medications, medical history and tobacco and alcohol use. Stool samples were processed for 16S rRNA gene sequencing and lipid analysis by gas chromatography-mass spectrometry. Alpha and beta diversity analyses and Procrustes randomization for associations were carried out. @*Results@#Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria were the most abundant taxa. Variation in microbiome composition was greater between individuals than within (p=0.001). Palmitic, oleic, stearic, and linoleic acids were the most abundant lipids. Variation in lipid composition was greater between individuals than within (p=0.040). Multivariate composition of the metabolome, but not microbiome, correlated with time (p=0.030). Total lipids, saturated lipids, and unsaturated lipids concentrations increased over time (p=0.012, p=0.008, p=0.023). Alpha diversity did not correlate with time (p=0.403). Microbiome composition was not associated with each samples’ metabolome (p=0.450). @*Conclusion@#Neonate gut microbiomes were unique to each neonate; respective metabolome profiles demonstrated generalizable temporal developments. The overall variability suggests potential interplay between influences including maternal breastmilk composition, amount consumed and living environment.

Hypoplastic coronary artery disease, as a cause of sudden death

ABSTRACT Hypoplastic coronary artery disease (HCAD) is a rare coronary artery anomaly that may be the cause of sudden death. It can involve a single or all coronary arteries. This anomaly may cause circulatory insufficiency leading to myocardial infarction. HCAD has no symptoms or may exhibit cardiovascular signs like syncope, dyspnea, chest discomfort, or dizziness. It is often diagnosed at autopsy, and early diagnosis is made with a coronary angiogram. We report HCAD as the cause of the sudden death of a 25-year-old female with a history of loss of consciousness following exertion. On autopsy, all the coronary arteries' lumen was narrowed with thin vessel walls. Histopathological examination shows an underdeveloped and missing muscular layer of the left anterior descending and circumflex coronary arteries' vascular wall. Many cases of HCAD diagnosed by radiographic imaging in living patients have been reported in the literature, but a structural anomaly of coronaries leading to HCAD has not been reported. We report a case of HCAD describing the histopathological examination findings of the vascular wall of coronary vessels illustrating the structural difference.

Overview on Dravaka Kalpana w.s.r. to Shankha Dravaka

Rasashastra is the Iatrochemistry of Ayurveda which deals with formulations containing herbals, minerals and metals. Various Kalpanas are mentioned in Rasashastra such as Pottali Kalpana, Kharaliya Kalpana, Parpati Kalpana. Dravaka Kalpana is one among them which is made out of predominately “Lavana- Kshara” Dravyas. Dravaka Kalpana is a liquid dosage form that is prepared either by using Agni or without the use of Agni. Shankha Dravaka is one such Dravaka Kalpana that is mentioned in the different classical texts. It is indicated in various diseases such as Gulma (abdominal lump), Shoola (pain), Yakrit Dosha (disorders of the Liver), Pliha (splenic disorders), Ashmari (calculus) etc. It is used in less dosage by diluting with water. Different Acharyas have mentioned different methods of its preparation. This article compiles review of Ayurvedic literature on Shankha Dravaka. This literature review is carried out to create the base for undertaking future research work because without research efficacy, the utility cannot be established

Atypical MYC rearrangement pattern of 3? deletion and 5? amplification along with independent IGH rearrangement: A case study

A spectrum of Cellular homolog of the v-myc oncogene (cMYC) alterations such as translocation, overexpression, mutation, and amplification plays an important role in lymphomagenesis, particularly in high-grade lymphomas, and are associated with prognostic significance. Accurate identification of cMYC gene alteration is important for diagnostic, prognostic, and therapeutic implications. With the application of different FISH (fluorescence in situ hybridization) probes that helped overcome the analytical diagnostic challenges as a result of variant patterns, we report rare, concomitant, and independent gene alterations in cMYC and Immunoglobulin heavy-chain gene (IGH) with detailed characterization of its variant rearrangement. Short-term follow-up post R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy seemed to be favorable. Accumulation of many more literature studies on such cases with their therapeutic implications would lead to the categorization of these cases as a separate subclass in large B-cell lymphomas followed by molecular targeted therapy.

Fear of cancer recurrence among cancer survivors in Singapore

INTRODUCTION@#Fear of cancer recurrence (FCR) among cancer survivors is a persistent and distressing psychosocial concern that affects recovery and quality of life. The prevalence of FCR in Singapore is unknown. This cross-sectional study was designed to examine FCR and identify factors associated with FCR in mixed-cancer survivors locally.@*METHODS@#Cancer survivors in remission (n = 404) were assessed for: FCR using the Fear of Cancer Recurrence Inventory (FCRI); emotional distress using the Hospital Anxiety and Depression Scale; and quality of life using the World Health Organization Quality of Life-BREF. Clinical and severe/pathological FCR was determined based on the severity scale of FCRI, known as FCRI-Short Form. Multivariate logistic regression was performed to examine factors associated with FCR.@*RESULTS@#The mean score on the FCRI was 59.5 ± 30.4. 43.6% of cancer survivors had clinical FCR and 32.1% had severe/pathological FCR. Younger age (odds ratio [OR] 0.952, 95% confidence interval [CI] 0.911-0.995, p < 0.05), higher educational status (OR 2.55, 95% CI 1.15-5.65, p < 0.05) and higher levels of emotional distress (OR 1.17, 95% CI 1.10-1.24, p < 0.001) were significantly associated with severe/pathological levels of FCR.@*CONCLUSION@#The present study is the first to determine levels of FCR among cancer survivors in Singapore. While the total FCR scores were similar to those of international studies, severe/pathological levels of FCR were found to be four times higher. These findings highlight a problem that is not widely recognised or acknowledged, but which deserves greater attention.

Outcomes of the Perplexed Surgical Management of Retinal Detachment in Eyes with Coloboma

Purpose@#To determine the anatomical and visual outcomes of retinal detachment in eyes with chorioretinal coloboma managed by pars plana vitrectomy, endolaser photocoagulation and silicone oil (SO) tamponade. @*Methods@#Retrospective review of 29 eyes of 29 patients with retinal detachment associated with chorioretinal coloboma. All the cases were managed by vitrectomy procedures concluding with SO tamponade. Encircling band was placed based on pre-operative evaluation and/or surgeon’s discretion. Endolaser photocoagulation was applied around the peripheral retina, all around the peripheral breaks and around the colobomatous area. The outcome measures were evaluated with regard to functional and anatomical success. @*Results@#The average age at the time of surgery was 21.76 ± 9.58 years (range, 10–50 years). The mean follow-up duration was 12.28 ± 4.8 months (range, 6–24 months). Primary attached retina was obtained in 21 / 29 (72.4%) eyes after single surgery. Re-detachment in 8 / 29 (27.6%) eyes which required revision surgery was the most frequent postoperative complication followed by raised intraocular pressure in 4 / 29 (13.8%) with SO in situ. Out of 29 eyes, 23 were followed up after the removal of SO. The mean duration of SO removal was 7.91 ± 3.9 months (range, 4–18 months). Implantation of encircling band, lens removal and cryotherapy provided no added advantage. At the final examination, improvement in vision was observed in 21 (72.4%) eyes and the anatomical attachment of the retina was attained in 27 (93.1%) eyes. @*Conclusions@#Complete pars plana vitrectomy, endolaser photocoagulation along with SO tamponade is effective for retinal detachment associated with chorioretinal coloboma. This technique improves the anatomical outcome and helps in regaining significant visual acuity.

Respectful maternity care for positive birthing experience at Pravara Rural Hospital

Background: Many women in developing countries experience disrespect and abuse during labour and delivery. Respectful maternity care (RMC) is considered as one of the basic reproductive health rights of the women. It is one of the essential components of LaQshya programme of Government of India. The aim of the study was to highlight the important components of the RMC, its implementation and its impact on patient turnover in the maternity unit of Pravara Rural Hospital Loni and review the literature on the subject.Methods: A prospective observational study was conducted for a period of one year from January 2019 to December 2019 at tertiary care hospital. The implementation of RMC was observed and important findings were documented. The patient turnover and cliental satisfaction was noted.Results: It was observed that all components of RMC were strictly followed in maternity unit of Pravara Rural Hospital Loni. The staff and doctors were trained and oriented towards importance of RMC. The patient turnover has increased exponentially year by year. The patient feedback system about the quality of care in labour and delivery ward shows overall satisfaction score of 4.3 on the 5-point Likert scale. There was a surveillance system that supervises and closely monitor the quality of care in labour room in general and RMC in particular.Conclusions: RMC is one of the important components of LaQshya certification process. Respectful maternity care is implemented at Pravara Rural hospital in its true spirit. It has resulted in gaining the faith and trust of the community, which is reflected through exponential rise in the number of deliveries taking place in the hospital.

Progressing haemolysis, elevated liver enzymes, low platelet count syndrome: near miss case

A 25 years old women presented in labour room with 30 weeks’ pregnancy in labour with breech with previous two caesarean section and scar tenderness with foetal bradycardia (FHR 90) and jaundice. After caesarean section in emergency hour she started bleeding in abdominal drain while uterus was well contracted. On investigation and examination diagnosed as HELLP syndrome, managed promptly by medical teams of three departments (obstetrician, anaesthesia and medicine).

Effect of methonolic extract of Vitex negundo on haloperidol induced catalepsy in albino mice

Background: Plants are being used in traditional medicine since history of mankind. The knowledge of these medicinal plants has accrued in the course of many centuries leading to medicinal systems in India such as Ayurveda, Unani and Siddha. Objective: In the present study, we evaluated the anticataleptic efficacy of Vitex negundo, a polyherbal formulation in haloperidol induced catalepsy in mice.Methods: Five groups (n=6) of male albino mice were used in the study. Catalepsy was induced by i.p. administration of haloperidol (1 mg/kg). The degree of catalepsy (cataleptic score) was measured as the time the animal maintained an imposed posture. We compared the anticataleptic efficacy of Vitex negundo (50, 100, 200 mg/kg) with standard received Pheniramine maleate 10 mg/kg, i.p.Results: In vehicle treated animals, haloperidol (1 mg/kg. i.p.) produced the maximum catalepsy at 180 min (46.78�78 min). Standard treated as Pheniramine maleate 10 mg/kg, i.p. shows maximum at 120 min. 19.24�32. Test herb, i.p. Methanolic extract of Vitex negundo (50, 100, 200 mg/kg, i.p.) significantly potentiated haloperidol induced catalepsy at each time interval, in a dose dependent manner. At dose 50, 100 and 200mg/kg, extract of Vitex negundo (Linn.) roots showed maximum cataleptic score 12.34�78, 14.43�43 and 15.43�67 min, respectively at 120 minutes in haloperidol treated animals.Conclusions: The present study indicates that the methanolic extract of Vitex negundo reduces haloperidol-induced catalepsy in mice.

Evaluation of Antihypertensive Efficacy of Intravenous Hydralazine and Intravenous Labetalol in the Management of Severe Preeclampsia and Eclampsia..

Hypertensive disorders of pregnancy are one of the most common obstetrical problems and affect 5-10% of all pregnancies. Severe preeclampsia is a multi-system disorder and causes many complications like intracranial haemorrhage, hypertensive encephalopathy, abruptio placentae, heart failure, pulmonary oedema and eclampsia. Intravenous hydralazine and labetalol are considered as first line antihypertensive agents for management of hypertensive crisis. The objective of this study was to compare efficacy of intravenous hydralazine and labetalol in lowering blood pressure in severe pregnancy induced hypertension, as well as to find out frequency of maternal adverse reactions and foetal impacts.METHODSThe study was conducted at Calcutta National Medical College and Hospital over a period of one year. 100 women with severe preeclampsia were included in the study and randomly divided into two groups of 50 each. One group received intravenous hydralazine while the other group was treated with intravenous labetalol. The time and number of doses taken to achieve target blood pressure were noted. Number of patients having persistent severe hypertension after receiving maximum drug dosage were also taken into account.RESULTSThe pre-treatment systolic blood pressure was 168.80 mmHg in hydralazine group and 173.64 mmHg in labetalol group whereas the diastolic blood pressure was 143.92 mmHg and 142.6 mmHg in hydralazine and labetalol group respectively. Mean time to achieve blood pressure control was 22.20 minutes in hydralazine group and 26.04 minutes in labetalol group. There were 3 cases of persistent severe hypertension in hydralazine group and 2 cases in labetalol group. No statistically significant difference was found between the two groups in terms of efficacy, maternal adverse effects and perinatal outcome. However, maternal tachycardia and headache was found to be significantly higher in patients treated with hydralazine.CONCLUSIONSThus, both hydralazine and labetalol are effective and safe antihypertensive drugs which can be used to treat pregnancy induced hypertensive crisis. No significant difference is found between these two agents.

A Study of Assessment of Cardiac Autonomic Functions after Yogasana and Pranayama

Introduction: Modern lifestyle, busy work schedule, lackof exercise, more expectancy generates stress in human life.Stress is a crucial factor in origin of diseases. Stress leads toautonomic imbalance. Yoga has very positive effects on stress.Yoga is now widely used for prevention and treatment ofvarious disorders and to achieve the physical, Physiological,Psychological, spiritual and social well being of the person.So this study is planned to see the effects of yoga on healthysubjects as an important preventive measure to remain awayfrom diseases. The present study was undertaken to showthe various effects of selective yogasana and pranayama oncardiac autonomic functions in healthy subjects between agegroup 31 to 60 years.Material and Methods: The subjects fulfilling the inclusioncriteria underwent the yogasana and pranayama sessions.Anthropometric data was collected. The cardiovascular statusof 45 healthy subjects was assessed by cardiac autonomicfunction tests before the start of and after 3 months ofyogasanaand pranayama practice daily for one hour. Theinstruments Diabetic Risk Profiler by Genesis HealthcareSystem Hydrabad, Handgrip dynamometer, digital bloodpressure apparatus, cold water tub were used. The testsconducted were resting heart rate, resting blood pressure, deepbreathing test(E/I ratio), orthostatic heart rate response (30/15ratio), valsalva ratio, sustained handgrip test, cold pressor testand blood pressure response to standing.Results: After yogasana and pranayama for three monthssignificant reduction in resting HR, SBP and DBP were found.Mean resting heart rate (HR) was decreased from 77.04/minto 71.38/min, mean SBP from 121mmHg to 117.51 mmHgand mean DBP from 83.42mmHg to 79.91mmHg. There wassignificant increase in parasympathetic reactivity parameterslike orthostatic HRR from 1.12 to 1.50, Deep breathing from1.20 to 1.52 and valsalva ratio from 1.24 to 1.67. There wassignificant decrease in sympathetic reactivity variables likesustained HGT Difference of diastolic BP (∆DBP) from 11.40to 7.73 mmHg, cold pressor test ∆DBP 11.67 to 7.71mmHgand BP response to standing Difference of systolic BP (∆SBP)from 10.71 to7.64 mmHg. There were no statistical significantchange observed in anthropometric parameters like body massindex (BMI) from 24.12 to 23.28 and waist hip ratio(WHR)from 0.87 to 0.85.Conclusion: It can be concluded that yogasana and pranayamahas beneficial effects on cardiac autonomic activities andreactivity. This lifestyle should be followed regularly as apreventive measure by the persons with cardiac diseasesto get relief and also healthy persons to remain away fromcardiovascular problems.

Impact of focality on prognostication of early and operable breast carcinomas of no special type

Background and Objectives: Multifocal/multicentric (MF/MC) breast carcinomas are not uncommon and its prognostic significance debated. We attempted to analyze the association of focality and prognostic factors in operated pT1 and pT2 breast carcinomas of no special type (NST). Materials and Methods: Retrospectively identified pathologically proven 124 unifocal (UF) and 49 MF/MC pT1 and pT2 breast carcinomas of NST over the past three years were compared in terms of clinical and pathological factors. Results: The patients with MF/MC NST tumors were more likely to undergo radical surgery (P = 0.028). The tumors showed higher incidence of lymphovascular invasion (P = 0.024), perineural invasion (P = 0.046), ductal carcinoma in situ component (P < 0.001), higher number of positive axillary lymph nodes (P < 0.001), and higher anatomical staging (P = 0.048) when compared to the UF counterparts. Morphological intertumoral heterogeneity was noted in MF/MC tumors in 16 of 49 cases (32.65%). Conclusion: Most published studies on MF breast cancers have included all histological types and varying definitions. We included only pathologically defined stages and a single histological type to ensure “purity” of the groups. Higher anatomic staging and morphological interlesional heterogeneity suggest that early MF/MC tumors represent multiple primaries with a different biology. Careful consideration of features of each focus needs to be considered when deciding appropriate adjuvant therapy and for accurately prognosticating these patients. Immunohistochemical and morphological (grade) heterogeneity between the different foci may pose problems with “prognostic stage grouping” these tumors according to the American Joint Committee on Cancer staging system (8th edition).