Vo l 1 1 • No . 2 • S e p–De c 2 0 2 3 A Publ ication of Himalaya Wel lness Company Scan this QR code to participate in the Happiness Zone Contest See page 25 and Win Prizes! Scan to read the e-version of Evecare
Evecare forte ™ (LIQUID, TABLET) • Regularizes endogenous hormone levels • Helps reduce the number of abnormal follicles – Corrects the cyclical rhythm • Helps in restoring ovulation – Improves fer tility rate • Insulin-sensitizing activity corrects ovarian dysfunction and other metabolic derangements associated with insulin resistance • Safe, polyherbal, and nonhormonal menstrual modulator In PCOS... Dosage Liquid: 2–4 teaspoonsful (10–20 ml) twice daily for 3 to 6 months. Tablet: 1 tablet twice daily for 3 to 6 months. Indication: PCOS Evecare forte–
i Evecare • Vol 11 • No. 2 • Sep–Dec 2023 Editorial Dear Doctor, Women endure several physical and psychological disturbances due to polycystic ovary syndrome (PCOS). In addition, the clinical manifestations of PCOS can affect organs such as the liver, the metabolic hub of the body. The latest reports suggest that women with PCOS are at an escalated risk of developing nonalcoholic fatty liver disease (NAFLD) compared with normal, healthy women. This issue of Evecare has a compilation of articles that talk about the role of PCOS-associated hyperandrogenemia in the development of NAFLD and patient education tips to effectively cope with PCOS symptoms. Also, excerpts of clinical studies that prove the efficacy and safety of Evecare forte Liquid in the management of PCOS and Liv.52 DS in the management of NAFLD are included. In addition, the awe-inspiring story of Ms Mahasweta Ghosh’s recent Marathon des Sables’ success and interesting articles on growing a kitchen garden and harnessing its enormous benefits are also a part of this issue. We hope you enjoy reading this collection of articles. Do participate in the Happiness Zone contest and win prizes (see contest details below)! — Editor Some of the interesting contest responses are featured on page 25. Kitchen Gardening Read more on page 26 Happiness Zone Contest! Tell us about your favorite activity for relaxing and rejuvenating. Access the link below or scan the QR code to fill in the details. https://forms.gle/ueYUFhAds4DLypQp6 Win Win prizes! ® Evecare
Evecare • Vol 11 • No. 2 • Sep–Dec 2023 ii Contents 20 1 7 14 16 15 Gynecologic Update . . . . . . . . . . 1 Nonalcoholic Fatty Liver Disease in Women With Polycystic Ovary Syndrome: Understanding the Hepato– Ovarian Axis Research at Himalaya . . . . . . . . . 3 Evecare forte Liquid in the Management of Polycystic Ovary Syndrome Safety and Efficacy of Liv 52 DS in the Management of Nonalcoholic Fatty Liver Disease Product Profile . . . . . . . . . . . . . . . . . 7 Doctors’ Feedback . . . . . . . . . . . . . 9 Advances in Gynecology . . 10 HDDC3 and SDC2: Potential Biomarkers in the Diagnosis of Polycystic Ovary Syndrome Drug Alert . . . . . . . . . . . . . . . . . . . . . . 11 Effect of Antimicrobial Exposure in Pregnancy on Adverse Pregnancy Outcomes and Admission Rate to the Neonatal Intensive Care Unit: A MultiCenter Cohort Study Conferences and Events . . . 11 Interview . . . . . . . . . . . . . . . . . . . . . . . 13 Dr Veena G Shinde Food Facts . . . . . . . . . . . . . . . . . . . . . 14 Dietary Modifications for Healthy Hair Patient Education . . . . . . . . . . . . 15 Tips to Effectively Manage Polycystic Ovary Syndrome In theWorld of Medicine . . . 16 Association Between Inflammatory Diet Index and Severe Nonalcoholic Fatty Liver Disease Similarity in Neurodegeneration Pattern Between Obese Individuals and Patients With Alzheimer’s Disease Early Childhood Lower Respiratory Tract Infections: A Risk Factor of Premature Adult Mortality Effect of Sleep Quality on Cardiovascular Disease–Free Life Expectancy Journal/Books . . . . . . . . . . . . . . . . 18 Superwoman . . . . . . . . . . . . . . . . . 20 Mahasweta Ghosh 13
iii Evecare • Vol 11 • No. 2 • Sep–Dec 2023 If you would like to subscribe to this magazine, please fill an online form You can access this form through https://tinyurl com/ EvecareSubscriptionForm OR SUBSCRIPTION Copyright © 2023 Himalaya Wellness Company All content in this journal/publication is the property of Himalaya Wellness Company and is protected by Indian and international copyright laws. Any other use, including the reproduction, modification, distribution, transmission, republication, display, or performance, of the content in this journal/publication, without written permission from the owner, is strictly prohibited. For permission to reproduce articles/information published in this journal/publication, please write to publications@himalayawellness.com 26 28 30 22 35 Ayurveda and Women’s Health . . . . . . . . . . . . . . 22 Apium graveolens Happiness Zone . . . . . . . . . . . . . 26 Kitchen Gardening: Harnessing Happiness From Nature’s Basket Sustainable Living . . . . . . . . . . 28 Go Green With a Sustainable Kitchen Garden Timeless Trends . . . . . . . . . . . . . . 30 Traditional Weaves From Gujarat Movies and Medics . . . . . . . . . 34 Gadgets . . . . . . . . . . . . . . . . . . . . . . . . 34 Recipes . . . . . . . . . . . . . . . . . . . . . . . . . 35 Creamy Celery Soup Cheese Celery Garlic Toast Laughter Time . . . . . . . . . . . . . . . . 36 Riddle Time . . . . . . . . . . . . . . . . . . . 36
Dosage
1 Evecare • Vol 11 • No. 2 • Sep–Dec 2023 Gynecologic Update Nonalcoholic Fatty Liver Disease inWomenWith Polycystic Ovary Syndrome: Understanding the Hepato–Ovarian Axis Research findings continue to hint at the correlation between polycystic ovary syndrome (PCOS) and hepatic diseases in women. PCOS, a disease characterized by hyperandrogenemia and ovarian dysfunction, is known to trigger nonalcoholic fatty liver disease (NAFLD).1 NAFLD, a condition with ≥ 5% fat accumulation in the liver, is considered the most common hepatic manifestation of PCOS. Several clinical studies reveal that NAFLD is more severe in women with PCOS, with higher rates of severe hepatocellular ballooning, fibrosis, and advanced fibrosis among them than that in those without PCOS.2 According to a few meta-analyses, women with PCOS have a 2-fold higher chance of developing NAFLD, independent of their BMI and the geographic region.2,3 The main risk factors for NAFLD in PCOS include hyperandrogenemia, insulin resistance (IR), obesity, chronic inf lammation, and genetic factors. As most women with NAFLD have IR, the association between NAFLD and IR has been widely accepted.2,3 This article discusses the role of PCOS-associated hyperandrogenemia in the manifestation of NAFLD. NAFLD Pathogenesis in a Hyperandrogenemic State A sustained increase in the gonadotropin-releasing hormone level in PCOS causes an increase in the secretion of luteinizing hormone (LH) and a decline in the secretion of follicle-stimulating hormone. An increased androgen effect on ovarian thecal cells because of the excessive LH activity leads to hyperandrogenemia, ovarian dysfunction, and metabolic disorders in women with PCOS.2 Hyperandrogenemia is an independent predictor of NAFLD in PCOS. The association between hyperandrogenemia and NAFLD risk in PCOS is supported by several biological mechanisms. Hyperandrogenemia can inf luence the development and progression of NAFLD in PCOS by affecting hepatic lipid metabolism and branchedchain amino acid metabolism and by causing inf lammation and an imbalance in apoptosis and autophagy.2 Impaired hepatic lipid metabolism In hyperandrogenic women with PCOS, excess androgens can suppress the transcription of the low-density lipoprotein receptor (LDLR) gene, thereby
Evecare • Vol 11 • No. 2 • Sep–Dec 2023 2 Nonalcoholic Fatty Liver Disease in Women With Polycystic Ovary Syndrome prolonging the half-life of very low-density lipoproteins and LDL. As a result, lipids accumulate in the liver, thus, increasing the risk of NAFLD.3 Inflammatory response Hyperandrogenemia can induce a low-grade inf lammatory state by increasing the transcripts of the androgen receptor. Excess androgens can induce mitochondrial β-oxidation imbalance, cause de novo lipogenesis, and exacerbate hepatic inf lammatory damage by upregulating the expression and release of tumor necrosis factor-a and interleukins 6 and 1β, thus contributing to the development of NAFLD.2,3 Visceral fat accumulation Increased androgen level can promote visceral fat accumulation by inhibiting the activation of adenosine monophosphate–activated protein kinase (AMPK)—a potent inhibitor of lipogenesis in adipose tissues. The release of the nonesterified fatty acids from visceral adipocytes and impaired adipocyte differentiation and adipokine formation lead to adipose tissue buildup in the abdomen. In obesity, due to lipodystrophy, the ability of the adipose tissue to store excess energy is also diminished, which causes the hepatocytes to store excess lipids.2,3 Apoptosis Androgens are known as proapoptotic agents that target many types of peripheral cells, including hepatocytes. Hyperandrogenism leads to hepatocyte damage through its apoptotic function, in women with PCOS, and therefore, contributes to an increased risk of NAFLD progression.4 Thus, hyperandrogenemia may directly or indirectly contribute to NAFLD in women with PCOS. The Importance of Medical Intervention Reports of a few patients with PCOS having ultrasonographic evidence of fatty liver also show concurrent abnormal levels of aminotransferases. Without timely diagnosis, such significant liver pathology could potentially go unrecognized for long periods in women who are at risk of progressive and severe hepatic diseases.4 Given the inf luence of PCOS on clinically significant liver diseases such as NAFLD, early detection of NAFLD is crucial, especially at a young age. Medical intervention at an early stage may decrease or even eliminate the possibility of NAFLD progression.4 Lifestyle Intervention Both PCOS and NAFLD can be managed by adopting lifestyle modifications such as increased physical activity and consumption of a low-calorie diet for weight management. However, if the condition worsens, the disease could progress to nonalcoholic steatohepatitis, and lifestyle modifications would become ineffective.2 Lifestyle modifications help maintain healthy weight, increase insulin sensitivity, decrease hyperandrogenemia, and reduce the harmful effects of endocrine and metabolic disorders on the liver in women with PCOS.2 References 1. Khan MS, et al. Int J Mol Sci. 2023;24(8):7454. 2. Wang D, He B. Diabetes Metab Syndr Obes. 2022;15:1281– 1291. 3. Wu J, et al. Reprod Health. 2018;15(1):77. 4. Kelley CE, et al. World J Gastroenterol. 2014;20(39):14172– 14184. Impaired hepatic lipid metabolism, apoptosis and autophagy imbalance, impaired branched-chain amino acid metabolism, and inflammation contribute to the development and progression of NAFLD in PCOS.2
3 Evecare • Vol 11 • No. 2 • Sep–Dec 2023 Research at Himalaya Evecare forte™ Liquid in the Management of Polycystic Ovary Syndrome Aim To evaluate the efficacy and safety of Evecare forte Liquid in the management of polycystic ovary syndrome (PCOS) Materials and Methods This was an interventional, open-label clinical study that included 40 women, aged 18 to 45 years, with signs and symptoms of PCOS such as irregular menstrual cycles, weight gain, biochemical/clinical hyperandrogenemia, and hirsutism. Women with a history of PCOS, with < 8 periods in the preceding year and clinical, biochemical, and/or ultrasonographic (USG) diagnosis were also included in the study. Women with organic lesions in the reproductive tract, especially any benign or malignant growth; extensive cervical erosion; cervical polyps; endometriosis; or severe cardiac, hepatic, or mental illnesses were excluded from the study. All women who met the inclusion criteria were prescribed Evecare forte Liquid at a dosage of 20 mL, BID, for 3 months. They were followed up at months 1, 2, and 3 during the study, and their clinical signs and symptoms, USG findings, and biochemical, hematological, and hormonal parameters were monitored each time. The menstrual parameters including duration of menstrual cycle and intermenstrual interval; clinical parameters including hair loss, acne, depression, deepening An excerpt of the clinical study conducted by Ahalya S (to be published) is featured here. of voice, and hirsutism; and other parameters including BMI, waist-to-hip ratio, and skin changes such as hyperpigmentation around the face and neck were evaluated. Results The treatment with Evecare forte Liquid brought about significant improvements in menstrual parameters. There were significant reductions in the duration of menstruation (P < .035) and the intermenstrual interval (P < .0299). The hematologic parameters including hemoglobin, total blood count, differential blood count, platelet count, and erythrocyte sedimentation rate; lipid profile values; and liver function parameters were within the normal range before and after the treatment. Table 1 shows the effect of Evecare forte Liquid on hormonal parameters before and after the treatment; there was a positive effect on the hormonal levels. The testosterone level reduced significantly (P < .0063) by the end of the study. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are the pituitary hormones that support ovulation (normal range: 5–20 IU/mL). The level of LH surges to 25 to 40 IU/mL before ovulation, and then returns to the normal level after ovulation. However, in PCOS, there may be an elevated LH to FSH ratio of 3:1. This helps in diagnosing PCOS. After the treatment with Evecare forte Liquid,
Evecare • Vol 11 • No. 2 • Sep–Dec 2023 4 Table 2 shows the effect of Evecare forte on the clinical parameters of PCOS. There was a significant reduction in hair loss and acne after the treatment with Evecare forte Liquid. There was a reduction from the at-entry values to month-3 values in the clinical parameters depression, deepening of voice, and hirsutism. No adverse effects were reported or recorded during the study. Discussion Evecare forte Liquid is a polyherbal formulation comprising extracts of Symplocos racemosa, Trigonella foenum-graecum, Sphaeranthus indicus, Nardostachys jatamansi, and Aloe barbadensis. S racemosa is reported to reduce the high androgen level in PCOS and prevent ovarian cell dysfunction, leading to an improvement in fertility. It also helps normalize progesterone and cholesterol levels, restore the histology of the ovarian tissue, and improve ovarian and uterine weight. T foenumgraecum helps normalize the significantly high levels of LH and FSH, observed in PCOS, and thus, regularizes the menstrual cycle. S indicus is reported to have androgen receptor–inhibitory action, and thus, helps reduce the elevated testosterone level. N jatamansi possesses antiandrogenic activity, and it helps reduce the signs and symptoms associated with hyperandrogenism such as hirsutism and hyperpigmentation. A barbadensis helps normalize estrous cyclicity, maintain steroid status, and improve the fertility status. Conclusion Thus, Evecare forte Liquid is safe and effective in the management of PCOS. Evecare forte Liquid in the Management of Polycystic Ovary Syndrome Table 1. Effect of Evecare forte Liquid on Hormonal Parameters Hormonal Parameter At Entry At the End of the Study Testosterone, ng/dL 67.37 ± 22.91 35.13 ± 37.3 — aP < .0063 LH, IU/mL 14.4 ± 6.12 10.05 ± 4.92 — aP < .0435 FSH, IU/mL 7.26 ± 1.67 6.4 ± 1.75 Serum Insulin, IU/mL 31.48 ± 20.68 31.67 ± 24.77 Progesterone, ng/mL 0.4 ± 0.5 0.25 ± 0.25 Estrogen, pg/mL 98.07 ± 71.32 69.25 ± 46.88 No. of Ovarian Follicles, n 21.33 ± 4.62 17.50 ± 5.27 — aP < .0252 Size of the Follicle, mm 11.68 ± 2.46 11.24 ± 1.27 Statistical test: Paired t test Values are represented as mean ± SD. aP compared with at-entry values. Significance was fixed at < .05. FSH, follicle-stimulating hormone; LH, luteinizing hormone. Table 2. Effect of Evecare forte Liquid on the Clinical Parameters of PCOS Parameter At Entry Month 1 Month 2 Month 3 Hair Loss (n = 29) 1.38 ± 0.49 1.14 ± 0.44 0.97 ± 0.19 0.9 ± 0.31; aP < .0264 Acne (n = 20) 1.15 ± 0.49 0.75 ± 0.44 0.65 ± 0.49 0.6 ± 0.5; aP < .0423 Depression (n =14) 1.07 ± 0.27 1 ± 0 0.86 ± 0.36 0.71 ± 0.47 Deepening of Voice (n = 10) 0.9 ± 0.32 0.9 ± 0.32 0.7 ± 0.48 0.5 ± 0.53 Hirsutism (n =14) 1.29 ± 0.61 1.14 ± 0.66 0.93 ± 0.73 0.71 ± 0.83 Statistical test: Friedman's test followed by Dunn’s multiple comparisons test. Significance was fixed at < .05. Values are represented as mean ± SD. aCompared with at-entry values. PCOS, polycystic ovary syndrome. there was a reduction in the LH level and also a trend toward a decrease in the FSH level, which is indicative of improvement in PCOS. The serum progesterone and estrogen levels also reduced. These significant changes in the hormonal parameters (eg, testosterone level) indicate the benefit of Evecare forte therapy. Also, USG findings revealed that the number of ovarian follicles and the size of the ovarian follicles reduced at the end of the study.
5 Evecare • Vol 11 • No. 2 • Sep–Dec 2023 Safety and Efficacy of Liv.52® DS in the Management of Nonalcoholic Fatty Liver Disease Aim To assess the safety and efficacy of Liv.52 DS Tablets in the management of nonalcoholic fatty liver disease (NAFLD) Materials and Methods This prospective interventional study included 60 patients of either sex (aged 18–65 y) who were diagnosed with NAFLD through clinical examination, laboratory testing, and ultrasonographic (USG) findings, and those who were willing to provide informed consent. Patients with severe metabolic disorders, hepatic or pancreatic carcinoma, allergies, systemic diseases, and genetic disorders and pregnant and lactating women were excluded from the study. A detailed medical history of all the patients was obtained, and symptom evaluation was performed at the first visit. Additionally, the patients were examined for the presence of steatohepatitis with hepatomegaly. All patients received 2 Liv.52 DS Tablets, BID, for 2 months. An excerpt of the clinical study conducted by Siregar G et al published in the European Journal of Clinical and Experimental Medicine is featured here. The patients were subjected to liver function tests (LFTs; aspartate transaminase [AST], alanine transaminase [ALT], alkaline phosphatase, γ-glutamyl transferase, serum bilirubin, and albumin), hepatomegaly screening (using USG), and NAFLD score at baseline and at the end of months 1 and 2. The NAFLD fibrosis score was assessed at each visit to determine the severity of fibrosis due to NAFLD. Statistical analysis was performed using GraphPad Prism software version 6.07 for Windows (GraphPad Software, CA, USA). The data about LFTs, biochemical investigations, and NAFLD scores were analyzed using ANOVA followed by Tukey’s multiple comparison test. Results It was observed that there was a reduction in the liver fibrosis score at month 1, and there was a further reduction in the score by month 2. Similarly, patients with indeterminate scores also demonstrated a reduction in the fibrosis score after the treatment with Liv.52 DS. This indicates the positive effect of Liv.52 DS in reducing liver fibrosis associated with NAFLD (Table 1). Table 1. Effect of Liv.52 DS on Liver Fibrosis (NAFLD Fibrosis Score) Scale N Baseline Month 1 Month 2 NAFLD Score < - 1.455 = F0–F2 33 Mean - 2.886 - 2.911 - 2.915 SD 1.044 1.061 0.8617 NAFLD Score - 1.455 – 0.675 = Indeterminate Score 27 Mean - 0.650 - 0.684 - 0.849 SD 0.484 0.543 0.667 NAFLD Score > 0.675 = F3–F4 0 0 0 0 Statistical test: ANOVA followed by Tukey’s multiple comparison test; values are represented as mean ± SD. Formula for NAFLD Score: - 1.675 + 0.037 × age (y) + 0.094 × BMI (kg/m2) + 1.13 × IFG/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio - 0.013 × platelet (× 109/L) - 0.66 × albumin (g/dL). NAFLD score was evaluated: NAFLD score < -1.455 = F0–F2; NAFLD score -1.455 to .675 = indeterminate score; NAFLD score > .675 = F3–F4. ALT, alanine transaminase; AST, aspartate transaminase; IFG, impaired fasting glucose; NAFLD, nonalcoholic fatty liver disease.
Evecare • Vol 11 • No. 2 • Sep–Dec 2023 6 At baseline, 75% of the patients had hepatomegaly (liver size > 16 cm), and 25% of the patients did not have hepatomegaly (liver size < 16 cm). After 2 months of treatment with Liv.52 DS, only 42% of the patients had hepatomegaly, and 58% of the patients did not have hepatomegaly (Table 2). After the treatment with Liv.52 DS, the liver size significantly reduced from 17.44 ± 1.9 cm at baseline to 17.29 ± 1.77 cm at the end of month 1 (P < .0001) and further reduced to 15.87 cm at the end of month 2 (Figure). After the treatment with Liv.52 DS, the AST level reduced from 60.33 ± 13.04 IU/L at baseline to 56.43 ± 15.47 IU/L at month 1 and further reduced to 54.12 ± 17.26 IU/L at month 2, with a significance of P < .0339. The ALT level was 70.68 ± 18.49 IU/L at baseline, and it reduced to 64.13 ± 22.07 IU/L at month 1 (P < .0215) and further reduced to 61.9 ± 22.7 IU/L at month 2 (P < .0022). Hematology and biochemical investigations showed that Liv.52 DS is a safe formulation. Though high-density lipoprotein and low-density lipoprotein levels were within the normal range, the total serum cholesterol and serum triglyceride levels were borderline high at screening, and they remained the same at the end of the study. There were no clinically significant adverse events reported during the entire study period. The overall compliance to the treatment was good, with no treatment discontinuation. Discussion The hepatoprotective activity observed in this study can be attributed to the synergistic action of the bioactive ingredients of Liv.52 DS—Capparis Table 2. The Effect of Liv.52 DS on Hepatomegaly Liver Size on Ultrasonographic Screening Baseline Month 1 Month 2 No. of Subjects, n (%) No. of Subjects, n (%) No. of Subjects, n (%) Hepatomegaly, > 16 cm 45 (75) 43 (72) 25 (42) No Hepatomegaly, < 16 cm 15 (25) 17 (28) 35 (58) Figure. Effect of Liv.52 DS on Liver Size, Determined Using Ultrasonography spinosa, Cichorium intybus, Solanum nigrum, Terminalia arjuna, Cassia occidentalis, Achillea millefolium, and Tamarix gallica. C spinosa prevents elevation in the levels of malondialdehyde (plasma and hepatic) and liver enzymes (AST and ALT). C intybus suppresses the oxidative degradation of DNA in tissue debris. S nigrum protects the DNA against oxidative damage and also acts as a potent scavenger of hydroxyl and diphenyl picrylhydrazyl radicals. T arjuna reduces cholesterol levels and is also useful in liver disorders. C occidentalis modulates hepatic enzyme levels. T gallica has a beneficial effect on liver glycogen and serum proteins. Conclusion The results of this study reveal that treatment with Liv.52 DS causes a significant improvement in hepatomegaly and liver function parameters such as AST and ALT. During the study period, there was no progression of liver fibrosis due to NAFLD. The hematological and biochemical findings of this study suggest that Liv.52 DS is effective and safe in the management of NAFLD. 20 25 5 10 15 0 Liver Size, cm Baseline Month 1 Month 2 Safety and Efficacy of Liv.52 DS in Nonalcoholic Fatty Liver Disease
7 Evecare • Vol 11 • No. 2 • Sep–Dec 2023 Product Profile Evecare forteTM (LIQUID, TABLET) For the effective management of PCOS Introduction Evecare forte Liquid is a phytopharmaceutical formulation recommended for the comprehensive management of polycystic ovary syndrome (PCOS). Composition Each 5 mL of Evecare forte Liquid contains: Extracts Lodhra (Symplocos racemosa) 41.25 mg Methi (Trigonella foenum-graecum) 40.22 mg Mundi (Sphaeranthus indicus) 18.57 mg Jatamansi (Nardostachys jatamansi) 8.59 mg Powder Kanyasaara (Aloe barbadensis) 3.87 mg Each Evecare forte Tablet contains: Extracts Lodhra (S racemosa) 165.00 mg Methi (T foenum-graecum) 160.89 mg Mundi (S indicus) 74.26 mg Jatamansi (N jatamansi) 34.38 mg Powder Kanyasaara (A barbadensis) 15.47 mg Clinical Pharmacology Evecare forte Liquid is a safe, polyherbal, and nonhormonal menstrual modulator for the effective and comprehensive management of PCOS. Evecare forte Liquid helps regularize endogenous hormonal status, correct the cyclical rhythm, and reduce the number of abnormal ovarian follicles. It improves ovulatory function and other metabolic derangements associated with insulin resistance through its insulin-sensitizing activity. Evecare forte Liquid helps regularize the menstrual cycle and corrects symptoms of hyperandrogenism such as hirsutism and hyperpigmentation. Further, it improves the chances of fertility and also helps reduce mood swings, anxiety, and depression associated with PCOS. Indication PCOS Dosage Liquid: 10 to 20 mL, twice daily, for 3 to 6 months, or as directed by the physician. Tablet: 1 tablet twice daily, or as directed by the physician. Adverse Effects No adverse effects have been reported. Contraindications No known contraindications. Special Precautions To be used with caution in individuals with estrogendependent tumors. Drug Interactions No clinically significant drug interactions have been reported.
Evecare • Vol 11 • No. 2 • Sep–Dec 2023 8 Product Profile Dear Doctor, If you prescribe Evecare forte™ (Liquid, Tablet) and Reosto® (Tablet) and would like to share your feedback, please write to us at publications@himalayawellness.com Thank you! The Editor—Evecare, Scientific Publications Division HimalayaWellness Company, Makali, Bengaluru 562162, Karnataka, India Product Feedback Reosto® (TABLET) Restores bone health Reosto, a phytopharmaceutical formulation, is recommended for the treatment of senile and postmenopausal osteoporosis, and in immobilized patients following bone fracture. The elemental calcium in Reosto helps increase bone mineral density (BMD) and serum calcium levels. Reosto inhibits bone resorption, favorably inf luences bone formation, increases bone mass, and prevents the risk of osteoporotic fractures. Composition Each Reosto Tablet contains: Pdrs. Guggulu (Commiphora wightii) 235 mg Godanti bhasma 120 mg Rasna (Pluchea lanceolata) 50 mg Bala (Sida cordifolia) 45 mg Arjuna (Terminalia arjuna) 45 mg Ashvagandha (Withania somnifera) .45 mg Kukkutandatvak bhasma 35 mg Processed in Vamsa (Bambusa arundinacea), Kumari (Aloe vera), and Dhanyaka (Coriandrum sativum). Clinical Pharmacology Reosto promotes remineralization of bones; exerts phytoestrogenic, calcium supplementation, antiinf lammatory, antioxidant, and adaptogenic actions; and controls associated risk factors. Reosto restores the increased level of alkaline phosphatase (indicating its beneficial effect on bone formation), and decreases the urinary excretion of pyridinoline, deoxypyridinoline, and hydroxyproline (indicating inhibition of bone resorption). Thus, Reosto inhibits bone resorption and favorably inf luences bone formation. Indications • Osteoporosis – Senile osteoporosis – Postmenopausal osteoporosis • Immobilization following fractures Dosage 2 Tablets twice daily, followed by 1 tablet twice daily as maintenance dose. Adverse Effects No adverse effects have been reported. Contraindications No known contraindications. Drug Interactions No significant drug interactions have been reported. Presentation Box of 2 blister-pack strips of 30 tablets each.
9 Evecare • Vol 11 • No. 2 • Sep–Dec 2023 Doctors' Feedback I have been prescribing Evecare® Capsule for female infertility issues for many years now. A significant number of women trying for conception have benefitted from the same. I have tremendous faith in the medicine and highly recommend it. I have prescribed Evecare® in several cases of dysmenorrhea and irregular menstrual cycles and found it truly effective. It is well-tolerated among young girls and women. I have been prescribing Evecare® for the past 15 years. I must say the product has given very good results in irregular menstruation and dysmenorrhea. The saying, “Old is gold” holds true for Evecare® Syrup. I have been prescribing Evecare® Syrup for more than 2 decades now in the treatment of infertility, dysfunctional uterine bleeding, pelvic inf lammatory disease, and as a regular uterine tonic. It is a very good product. Evecare® is a highly effective medicine; it has given good results in abnormal uterine bleeding and infertility. Also, the product has no side effects. I have been prescribing Evecare® and Evecare® forte for various menstrual problems and polycystic ovary disease, respectively. The products have shown wonderful results. Dr Rachna Jindal Goel New Delhi, India Dr Monika Singh Samastipur, Bihar, India Dr Meera Bandil Morena, Madhya Pradesh, India Dr Rama Shastri New Delhi, India Dr Priti Lata Ranchi, Jharkhand, India Dr Nidhi Pradhan Neemuch, Madhya Pradesh, India ® Evecare
Evecare • Vol 11 • No. 2 • Sep–Dec 2023 10 Advances in Gynecology The HD domain coding 3 (HDDC3) gene is a cytosolic nicotinamide adenine dinucleotide phosphatase– coding gene that regulates ferroptosis, involved in the development of polycystic ovary syndrome (PCOS). The syndecan 2 (SDC2) gene is a heparan sulfate proteoglycan–coding gene that facilitates T-cell proliferation. The downregulation of these 2 protein-coding genes is hypothesized to be associated with PCOS and immune dysregulation during PCOS. Hence, a study was conducted to identify the expression of HDDC3 and SDC2 biomarkers in PCOS and validate their association with immune dysregulation in PCOS. Screening and Identification Strategy Five datasets (3 microarray datasets and 2 RNA sequencing datasets) were selected for the analysis. The microarray datasets contained granulosa cell (GC) samples from 19 patients with PCOS and 15 controls. The RNA sequencing datasets contained GC samples from 7 patients with PCOS and 7 controls. The datasets were subjected to the identification of differentially expressed genes and functional enrichment analytical assays. The Least Absolute Shrinkage and Selection Operator logistic regression model and the Support Vector Machine Recursive Feature Elimination algorithm were used to identify the target biomarkers. The HDDC3 and SDC2 biomarkers identified in this study showed > 0.8 area under the curve, indicating their potential predictive abilities in PCOS. Differential expression studies showed significantly low expression of HDDC3 and SDC2 in the GC samples of patients with PCOS compared with that in the control groups. HDDC3 and SDC2 Potential Biomarkers in the Diagnosis of Polycystic Ovary Syndrome Validation of the biomarkers in clinical samples The expression of HDDC3 and SDC2 biomarkers in clinical GC samples from 5 patients with PCOS and 5 controls was verified using quantitative reverse transcription polymerase chain reaction. It was identified that HDDC3 and SDC2 were significantly downregulated in GC samples of patients with PCOS compared with that of controls, thereby showing consistency with the bioinformatics analysis results. Immune Cell Infiltration Analysis The infiltration of immune cells around GCs in PCOS was predicted using the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts algorithm. The resting and memory CD4 T cells and neutrophils dominated in both PCOS and control groups. A significant difference was detected in the infiltration of activated mast cells and eosinophils between the groups, indicating the potential role of mast cells and eosinophils in the pathogenesis of PCOS. Relationship of biomarkers with infiltrating immune cells A correlation analysis revealed a positive correlation of HDDC3 with T-regulatory cells, activated mast cells, and monocytes, but a negative correlation with activated memory CD4 T cells; and a positive correlation of SDC2 with activated mast cells, plasma cells, and M2 macrophages, but a negative correlation with eosinophils and neutrophils. Thus, HDDC3 and SDC2 were identified as potential biomarkers of PCOS and their potential interactions with immune cells during the pathogenesis of PCOS were determined. Source: Na Z, et al. J Ovarian Res. 2022;15:80.
11 Evecare • Vol 11 • No. 2 • Sep–Dec 2023 Effect of Antimicrobial Exposure in Pregnancy on Adverse Pregnancy Outcomes and Admission Rate to the Neonatal Intensive Care Unit: A Multi-Center Cohort Study Drug Alert Events Venue-Based Conferences Event: 2024 Maternal-Fetal Imaging Advances in OB-GYN Ultrasound Date: January 12 to 14, 2024 Venue: San Antonio, TX, USA For more details, visit: https://conferenceindex.org/ ••• Event: OB/GYN Clinical and Surgical Updates: Staying Current and Ahead of the Curve 2024 Date: February 5 to 8, 2024 Venue: Napa, CA, USA For more details, visit: https://ce.mayo.edu/ ••• Event: 20th Annual Women's Health Update 2024 Date: March 21 to 23, 2024 Venue: Scottsdale, AZ, USA For more details, visit: https://ce.mayo.edu/ ••• Event: GYNEC 2024. 2nd Edition of Global Conference on Gynecology & Women’s Health Date: March 21 to 23, 2024 Venue: Singapore For more details, visit: https://gynecology. magnusconferences.com/ ••• The objective of this study was to explore the association between antimicrobial exposure during pregnancy and pregnancy outcomes. This multicentric retrospective cohort study on pregnant patients (N = 370) was conducted in 22 tertiary care hospitals in China. Adverse pregnancy outcomes and admission rate of neonates to the neonatal intensive care unit (NICU) were considered. The effect of antimicrobial exposure on the outcomes was assessed using a multivariate logistic regression model. The use of first-generation cephalosporins during pregnancy was associated with a significantly higher risk of adverse pregnancy outcomes (P = .007) and admission of the neonates to the NICU (P = .009), compared with the use of third-generation cephalosporins, after adjusting for gestational age at exposure to the antimicrobial agents, cesarean section, and antimicrobial dose. Similarly, higher risks of adverse pregnancy outcomes and NICU admission rate were observed among women who were on first-generation cephalosporins compared with mothers with no antimicrobial use. The use of both first- and third-generation cephalosporins was associated with an increased risk of adverse pregnancy and neonatal outcomes. In addition, first-generation cephalosporins were associated with an increased risk of adverse pregnancy and neonatal outcomes compared with third-generation cephalosporins. Source: Li Y, et al. Infect Drug Resist. 2023;16:2441–2451.
Doctor’s Corner Introducing A page in every issue of Evecare magazine will be reserved for your contributions. You could write to us about… For more information, write to us at publications@himalayawellness.com We look forward to hearing from you! Your or your family’s achievements A heartwarming experience with a patient A summary of a rare and interesting case
13 Evecare • Vol 11 • No. 2 • Sep–Dec 2023 Interview Extrauterine Manifestations of Polycystic Ovary Syndrome Doctor, women with polycystic ovary syndrome (PCOS) are often diagnosed with one or the other metabolic disease. What are the most common metabolic diseases associated with PCOS? That is correct. Various unhealthy lifestyle factors lead to the development of heterogeneous metabolic diseases in women with PCOS. Metabolic manifestations such as insulin resistance (IR), obesity, dyslipidemia, and hyperandrogenism are frequently diagnosed in women with PCOS. Doctor, how is insulin sensitivity affected in women with PCOS? PCOS can trigger IR in the peripheral tissues of the skeletal muscle and adipose tissue and affect the functioning of the insulin receptors, thereby impairing glucose metabolism. Most women with PCOS who have impaired glucose tolerance are at a higher risk of developing type 2 diabetes mellitus. Doctor, are there any hepatic manifestations of PCOS? Yes, PCOS can also trigger liver diseases. PCOS affects the normal functioning of the mitochondria, leading to oxidative stress. Persistent oxidative stress can aggravate hyperandrogenism, IR, and hepatic lipid accumulation, which can contribute to hepatic steatosis and nonalcoholic fatty liver disease in women with PCOS. Doctor, could you suggest a few ways to simultaneously manage metabolic diseases and PCOS? Lifestyle modification through diet recalibration and regular physical activity are considered as effective nonpharmacologic approaches to manage metabolic diseases and PCOS. Adopting a low-carbohydrate diet, or diets rich in complex carbohydrates, fiber, and monounsaturated fats is beneficial. A calorie-restricted diet is the best choice for managing IR. Doctor, do you have any therapeutic recommendations to alleviate PCOS and the associated symptoms? In addition to dietary interventions, I generally recommend Evecare forte, a nonhormonal menstrual modulator from Himalaya Wellness Company, for the effective management of PCOS. Evecare forte helps regularize endogenous hormonal status, corrects the cyclical rhythm, and reduces the number of abnormal follicles. Evecare forte improves ovulatory function and other metabolic derangements associated with IR through its insulin-sensitizing activity. Evecare forte also alleviates the symptoms of PCOS including hirsutism, hyperpigmentation, mood swings, anxiety, and depression and improves fertility. Dr Veena G Shinde, MD, DGO Consultant Obstetrician and Gynecologist, Infertility Specialist Shinde's Medicare Hospital Pvt Ltd Mhatarpada Jai Mata Bhavani Road Before Ramesh Nagar, Amboli Andheri West Mumbai 400061, Maharashtra India We thank our field correspondents for their inputs and support. Avadesh Kumar Pathak, Regional Manager Sandeep Kumar Dinesh Kumar Chaubey, Pharma Sales Officer HimalayaWellness Company —Editor
Evecare • Vol 11 • No. 2 • Sep–Dec 2023 14 Food Facts Hair follicles require protein, trace elements, and vitamins for optimal metabolic activity. Deficiency of these components affects hair health, and eventually leads to hair loss. Thus, hair health is closely related to diet.1,2 Essential Nutrients for Hair Growth Protein Protein that contains sulfur-based amino acids (eg, cysteine and methionine) is a precursor for keratin synthesis. Insufficient intake of such protein leads to fragility and loss of hair. Cottage cheese; yogurt; fish; meat; soybeans; lentils; beans; peas; broad beans; buckwheat; hulled barley; brown rice; nuts; eggs; and seeds of pumpkin, sunf lower, and sesame are foods that have sulfur-containing amino acids.2 Vitamins Vitamins A, B, C, and D are key for hair health. Vitamin A (retinoids and carotenoids) moisturize the hair and protect it from becoming fragile. Vitamin A deficiency causes ichthyosis-like skin changes and is often associated with telogen eff luvium and hair fragility. Eggs, chicken, fish, meat, green leafy vegetables, and nuts are good sources of vitamin A.2,3 Biotin (vitamin B7) is an essential vitamin that helps in the production of keratin, and its deficiency might lead to hair loss. Foods containing biotin are milk, sweet potatoes, broccoli, meat, egg yolk, yeast, and nuts.2,4 Pantothenic acid (vitamin B5) prevents early hair graying, can restore the natural hair color, and moisturizes the hair. It also plays a role in hair follicular cell division, regulates the functioning of the sebaceous glands, and accelerates melanin production. Some of the foods rich in vitamin B5 are mushrooms, cauliflower, soya, eggs, baking yeast, whole grains, beans, milk, and green leafy vegetables.2 Vitamin C helps in hair shaft elongation and triggers hair growth. Vitamin C deficiency results in hair shaft abnormalities. Parsley, kale, horseradish, peppers, brussels sprouts, broccoli, caulif lower, spinach, black currants, red currants, strawberries, kiwi, and citrus fruits contain vitamin C.2,3 Minerals Minerals such as zinc, iron, copper, and silicon inf luence hair growth. Zinc enables protein and fat metabolism, and at the same time, promotes hair follicle formation and hair growth. Zinc deficiency suppresses hair growth and can lead to telogen eff luvium. Iron is a major component of hemoglobin that supplies energy to the matrix cells in the hair bulb, which aids in hair growth. Copper is essential for keratin fiber strength. Its deficiency results in brittle hair, and could lead to early graying. Silicon is responsible for hair growth and shine. The food sources of these minerals are meat, fish, soya, white beans, parsley, dried apricots, and figs.2,3 Including these nutrients in the daily diet is thereby essential to maintain hair health. References 1. Trüeb RM. Int J Trichology. 2021;13(6):1. 2. Goluch-Koniuszy ZS. Prz Menopauzalny. 2016;15(1):56–61. 3. Ruiz-Tagle SA, et al. Our Dermatol Online. 2018;9(3):320– 328. 4. Health Essentials. Is biotin as good as advertised for your hair loss? https://health.clevelandclinic.org/. Published October 26, 2022. Accessed July 27, 2023. Dietary Modifications for Healthy Hair
15 Evecare • Vol 11 • No. 2 • Sep–Dec 2023 Patient Education Tips to Effectively Manage Polycystic Ovary Syndrome Polycystic ovary syndrome (PCOS) is the most common endocrine disorder seen among women of reproductive age. The most common signs of PCOS include menstrual abnormalities, fertility issues, obesity, hirsutism, acne vulgaris, and androgenic alopecia.1 Here are a few tips that can be recommended to your patients to help cope with PCOS. Adopting a Healthy Diet In most women with PCOS, insulin production is disrupted, which may lead to hormonal imbalance. This causes acne, excess facial or body hair, and irregular menstruation that may even affect an individual’s mental health. Consuming low glycemic index (GI) foods can help regulate the insulin level. Low GI foods include oats, sweet potatoes, legumes, lentils, green leafy vegetables, and fruits (eg, cherries, plums, apples, and strawberries). Oily fish (eg, salmons, sardines, and mackerels), avocadoes, and olive oil are rich in essential fatty acids that can help normalize sex hormone levels, and thus, regulate the menstrual cycle.2 Exercising Regularly Obesity can increase the overall risk of developing long-term health issues from PCOS; this can be mitigated by maintaining a healthy body weight. Engaging in aerobic exercises (eg, walking and running) regularly will help in overall health and fitness. Focusing on lower abdominal exercises will help reduce belly fat, and thus, reduce PCOS symptoms.3 Keeping the Body and Mind Stress-Free Many PCOS symptoms such as excessive hair growth, acne, and alopecia can make women self-conscious and lower their self-esteem. Yoga, pranayama and meditation are excellent ways to help ease the symptoms of anxiety and depression.4 Preparing a to-do list for the entire day can help reduce anxiety and make the day productive. Setting aside some time for self-care regularly is another effective way to manage stress. Engaging in a gratifying hobby such as going on a walk, listening to music, and reading a book of choice can help bring joy and rejuvenate the mind and body.4,5 Getting Proper Rest An average adult needs about 7 to 9 hours of sleep at night. If a person has trouble sleeping because of anxiety issues, controlled breathing can be an extremely beneficial technique for relaxing both the body and mind.5 The symptoms of PCOS can be effectively managed by maintaining an active and healthy lifestyle. Making a few lifestyle changes can be highly beneficial in coping with the condition. References 1. Chaudhari AP, et al. Indian J Mental Health. 2018;5(2):209– 216. 2. Gatenby L. Top tips to cope with PCOS. https://www. nutritionist-resource.org.uk/. Published July 9, 2018. Accessed July 13, 2023. 3. The Art of Living. 5 Simple home remedies for PCOS. https://www.artofliving.org/. Accessed July 13, 2023. 4. Patient. How to cope with a PCOS diagnosis. https:// patient.info/news-and-features/how-to-cope-with-a-pcosdiagnosis. Updated May 26, 2021. Accessed July 13, 2023. 5. Patient. How to practise self-care. https://patient.info/ news-and-features/what-is-self-care. Updated November 15, 2018. Accessed July 13, 2023. Layout Complete
Evecare • Vol 11 • No. 2 • Sep–Dec 2023 16 In the World of Medicine A recent study published in BMC Medicine examined the association between Energy-adjusted Diet Inf lammatory Index (E-DII) score and severe nonalcoholic fatty liver disease (NAFLD) in middle-age and older adults. This prospective cohort study included 171,544 participants from the UK Biobank. The E-DII score was determined using 18 food parameters and classified into 3 categories: (i) very/moderately anti-inf lammatory diet (E-DII < − 1), (ii) neutral diet (E-DII ≥ − 1 to ≤ 1), and (iii) very/moderately proinf lammatory diet (E-DII > 1). Association between the E-DII score and the incidence of severe NAFLD was evaluated using Cox proportional hazard models. It was found that 1489 participants developed severe NAFLD over a median follow-up of 10.2 years. Patients in the very/moderately proinf lammatory diet category were at 1.54 times higher risk of severe NAFLD compared with those in the very/moderately anti-inf lammatory diet group. It was identified that a higher E-DII score was linked with a higher NAFLD risk. These findings suggest that proinf lammatory diets were associated with a higher risk of severe NAFLD, independent of confounders such as metabolic syndrome components (ie, central obesity, diabetes, hypertension, low level of high-density lipoprotein, and high triglyceride). Source: Petermann-Rocha F, et al. BMC Med. 2023;21:123. A recent study published in the Journal of Alzheimer’s Disease investigated the correlation between the degree of similarity in brain atrophy patterns in obesity and Alzheimer’s disease (AD). The study was performed using samples from 1300 individuals from 4 groups: (i) patients with AD, (ii) healthy controls (HCs), (iii) obese but otherwise healthy individuals, and (iv) lean patients with AD. It was found that obesity and AD affected gray matter cortical thinning in similar ways. The thinning in the right temporoparietal cortex and the left prefrontal cortex was similar in both AD and obesity groups, but not with amyloid-β or tau distribution, indicating obesity as a significant risk factor of AD. Researchers postulated that cortical thinning may be a sign of neurodegeneration. The study results also highlight the importance of reducing excess body weight in obese individuals to decrease the subsequent risk of neurodegeneration and AD. Source: Morys F, et al. J Alzheimer’s Dis. 2023;91(3):1059–1071. Similarity in Neurodegeneration Pattern Between Obese Individuals and Patients With Alzheimer's Disease Association Between Inflammatory Diet Index and Severe Nonalcoholic Fatty Liver Disease
17 Evecare • Vol 11 • No. 2 • Sep–Dec 2023 A recent study published in The Lancet evaluated the association between early childhood lower respiratory tract infections (LRTIs) and the risk of premature adult mortality due to respiratory diseases. This longitudinal observational study included data of 3589 participants from the Medical Research Council, the National Survey of Health and Development (England, Scotland, and Wales). They were followed up through the ages of 26 to 73 years. Of the 3589 participants, 913 participants had LRTIs during early childhood (at < 2 y of age); they were at an increased risk of mortality due to respiratory diseases by the age of 73 years than those who did not have LRTI in early childhood (P = .021). These findings suggest that children with LRTIs by 2 years of age were almost twice as likely for an increased risk of premature death from respiratory diseases as adults, and these infections account for one-fifth of respiratory-cause deaths. This association remained even after adjusting for multiple markers of childhood socioeconomic conditions and adult smoking. Childhood LRTIs were not associated with other causes of death, thus suggesting a direct connection between early childhood LRTIs and the development or prognosis of adult respiratory diseases, such as chronic obstructive pulmonary disease. Source: Allinson JP, et al. Lancet. 2023;401(10383):1183–1193. A study published in BMC Medicine determined the differences in cardiovascular disease (CVD)–free life expectancy in people with poor sleep profiles. The self-reported sleep data of 308,683 middleaged adults were retrieved from the UK Biobank. Of these, the data of 140,181 patients had captured primary care and inpatient records too. Their (n = 140,181) clinical sleep disorders were classified into insomnia, sleep-related breathing disorders, and other sleep disorders. The CVD-free life expectancies in women and men with poor sleep and healthy sleep were 31.46 and 33.26 and 27.96 and 30.27 years, respectively. Men with clinical insomnia or sleep-related breathing disorders lost 3.84 or 6.73 years of CVD-free life, respectively. Women with sleep-related respiratory difficulties or other sleep disorders lost 7.32 or 1.43 years of CVD-free life, respectively. This study’s findings suggest that poor sleep is negatively associated with CVD-free life, especially in patients with sleep-related breathing disorders. Source: Huang BH, et al. BMC Med. 2023;21(1):75. Early Childhood Lower Respiratory Tract Infections: A Risk Factor of Premature Adult Mortality Effect of Sleep Quality on Cardiovascular Disease–Free Life Expectancy
Evecare • Vol 11 • No. 2 • Sep–Dec 2023 18 Books Journal Title: British Journal of Obstetrics and Gynaecology Publisher: Wiley Online Library The British Journal of Obstetrics and Gynaecology (BJOG) is the official journal of the Royal College of Obstetricians and Gynaecologists (RCOG), and it is published monthly. The journal publishes original and peer reviewed articles in obstetrics and gynecology on topics such as contraception, urogynecology, fertility, oncology, and clinical practice. The journal also publishes articles under the categories expert commentaries, journal club, and continuing professional development and continuing medical education (CPD/CME); perspective articles; and digital content such as audio podcasts and video abstracts. Title: Problem-Based Obstetric Ultrasound Editors: Amar Bhide, et al Edition: 2nd edition Publication Date: December 3, 2019 Number of Pages: 166 Publisher: CRC Press The book Problem-Based Obstetric Ultrasound contains a series of clinical cases that address and illustrate difficult problems in obstetric ultrasound. With a strongly didactic approach, the book is meant to help trainees in the field of maternal–fetal medicine and obstetrics to appreciate the potential pitfalls and recognize rare presentations. Each case presented is thoroughly discussed first, followed by a description of the treatment algorithms, and concluded with sample ultrasound scans for clear understanding. Also, each case contains learning objectives along with a short list of references and background reading. Title: An Invisible Thread Publication Date: 2011 Publisher: Howard Books/ATRIA Books Number of Pages: 260 An Invisible Thread is an inspirational true story of Laura Schroff, a busy sales executive, and Maurice, an 11-yearold panhandler. One fine day, Laura accidently meets Maurice who is a homeless boy. He asks Laura for some money as he is hungry. Laura does not pay heed to his call initially and keeps walking. But an inner instinct stops her, and Laura offers to buy him lunch. Both start sharing their life stories and immediately feel connected; they go on to develop an invisible, unbreakable bond. Thereafter, Laura continues meeting Maurice for dinner every week. It seems as if they were destined to meet and both find solace in each other’s company. This heartening story depicts the beautiful bond between two unknown individuals and the far-reaching benefits of kindness. Image source: https://images.app.goo. gl/oxYiqDh9bxYyiRG27 Image source: https:// www.publishersweekly. com/9781451642513 Image source: https://www. taylorfrancis.com/books/ mono/10.1201/9780429156694/ problem-based-obstetricultrasound-amar-bhide-asmakhalil-aris-papageorghiou-susanapereira-shanthi-sairam-baskythilaganathan
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