abdominal obesity : the risks factors .redustim, a medical device solution

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Abdominal obesity: the risks factors

Redustim: a medical device solution

Company Profile

Stéphanie Audran CEO European Office

PARIS - France

Clinical initial proof of concept

Genetic profiling Finalization of a product portfolio addressing the needs of aesthetic

and medical professionals

1998 2002 2009 2016

OVER A DECADE OF ADVANCED RESEARCH DEDICATED TO BIOMAGNETIC STIMULATION HEALTH APPLICATIONS

History

In 12 years, our Group becomes a large entity, by developping its worlwide activities.

Several thousands of professionals were equipped in France and abroad. Well known beauty centers trusted our technology and are using our devices to better serve their patients.

Filiale GCC : 4 personnes Head office Paris Training center Paris R&D and Production Tunis Digital office Casablanca GCC office Dubaï

DUBAI OFFICE

A whole group dedicated to fat reduction

Developer, manufacturer of medical equipment to reduce health risks related to abdominal fat. +15 years at the service of beauty and health industries professionnals. BioMagnetic field for a unique lipolytic action.

Non-aggressive, non-invasive with no secondary effect.

Group presentation

BEAUTY

FORM

HEALTH

SHAPE

SPORT

OBESITY

OUR GCC TARGET

Various application fields

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LipiDrainor

BodySculptor exCell+

BodySculptor intégral+ MyoSculptor

OsmoSculpt

Our solutions in the beauty industry

BIOMAGNETIC FIELD + MICROPRESSURE

BIOMAGNETIC FIELD

Our solutions in the health industry

FRANCE 500 equiped centers

Aesthetic sector:

• Beauty centers

• Spas

• Hotels

Health sector:

• Aesthetic Doctors

• Nutritionists & Dietitians

• Cardiologists

• Gynecologists

• Physiotherapists

EXPORT 2000 equiped centers

Created in 2006, the Export department is rapidly expanding with a presence already in about 15 countries mostly in Europe and Maghreb.

Other Export contracts are in the course of negotiation on markets with great potential in Emirates thanks to our subsidiary based in Dubai.

Our distribution network

+2500 Equiped centers

around the world

Years in the beauty and

health industry

Scientific and

medical studies

French and international

patents

+15 +10 +5 Companies promoting

BioMagnetic Fields

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Nowadays …

Abdominal obesity

Context and Risks Dr Philippe BLANCHEMAISON

Angiologist – Phlebologist PARIS - France

Obesity is rising unrelentingly in all industrialized countries !

Pooled analysis of 1698 population-based measurement studies with 19·2 million participants – source The Lancet. If post-2000 trends continue, by 2025, global obesity prevalence will reach 18% in men and surpass 21% in women; severe obesity will surpass 6% in men and 9% in women.

Obesity and overweight contribute to: v

CARDIOVASCULAR DISEASE

DIABETE CANCER

Obesity: the evil of the century

Abdominal obesity: the main cause of metabolic syndrome

Abdominal obesity increases hypertension

Abdominal obesity: a cause of cardiovascular disease and stroke

Abdominal obesity: cause of infertility

Big belly = 5 times more likely to have diabetes

Abdominal obesity causes risk of impotence

Abdominal obesity: risks of mortality doubled

Abdominal obesity care of the cirrhosis

Abdominal obesity improve cancer risks

Abdominal obesity: did you know?

Abdominal or visceral fat is:

• located in the abdominal cavity around the organs.

• a very high risk factor for heart disease and type 2 diabetes.

Abdominal obesity: a source of serious medical complications

Abdominal obesity:

• characterized by a large waist circumference.

• clearly reduces life expectancy.

• numerous complications (high blood pressure, high cholesterol, heart attack, stroke and certain cancers).

• indicator of visceral fat.

Metabolic syndrom

=> Existence of many abnormalities due to abdominal fat accumulation Concerned if you have at least 3 of the following abnormalities:

=> Generally associated with being overweight.

Waist circumference

> 102 cm for men and > 88 cm for women

Triglycerides

> 1.5 g/l

HDL Cholesterol

< 0.5 g/l for men and < 0.4 g/l for women

Fasting glucose

> 1 g/l

Blood pressure

> 13/8.5

Criteria and thresholds defined by the WHO and NCEP ATP III

Which therapeutic strategy against abdominal obesity ?

REDUSTIM, THE EFFICIENT PHYSICAL METHOD

THAT CAN REDUCE UP TO 2 CLOTHING SIZES

WITHOUT PAIN NOR SIDE EFFECTS.

5 critères d’évaluation du syndrome métabolique

Abdominal obesity in GCC & consequences for the population

Dr Afra bin KATTA Head of Nutrition Rashid hosp.

Dubaï Health Autority

Dietary and lifestyle recommandation

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ADRENAL OVARY THYROID LIVER

The 4 new body type

General objectives

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1/ To provide guidelines for health professionals, for the nutritional management of OBESITY.

2/ To provide the efficacy of a comprehensive lifestyle intervention program, to facilitating weight loss or maintenance of lost weight.

Projected prevalence of overweight, UAE

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Screening assessment

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Anthropometric Measurements

Description Women Men

Essential fat 10–13% 2–5%

Average 25–31% 18–24%

Obese 32%+ 25%+

Fitness 21–24% 14–17%

Athletes 14–20% 6–13%

Anthropometric measurements

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Disease Risk* Relative to Normal Weight and Waist Circumference

BMI (kg/m²)

Obesity Class

Men 102 cm (40 in) or less Women 88 cm (35 in) or less

Men > 102 cm (40 in) Women > 88 cm (35 in)

Underweight < 18.5

- -

Normal 18.5–24.9

- -

Overweight 25.0–29.9

Increased High

Obesity 30.0–34.9 I High Very High

Severe Obesity

35.0–39.9 II Very High Very High

Extreme Obesity 40.0 + III Extremely High Extremely High

* Disease risk for type 2 diabetes, hypertension, and CVD. + Increased waist circumference also can be a marker for increased risk, even in persons of normal weight.

There are various ways of measuring abdo obesity

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1. Waist Circumference: >102 cm (40 in) in men and >88 cm (35 in) in women

2. Waist–hip Ratio: the circumference of the waist divided by that of the hips of >0.9 for men and >0.85 for women

For example: A waist measurement of (68.6 cm) divided by a hip measurement of (91.4 cm) would calculate to a WHR of 0.75.

3. Waist-to-height Ratio

Formula Waist to height ratio (WHtR) = ( Waist circumference / Height ) x 100

MEN: Ratio less than 35: Abnormally Slim to Underweight-Ratio 35 to 43: Extremely slim-Ratio 43 to 46: Slender and Healthy-Ratio 46 and 53: Healthy, Normal Weight-Ratio 53 to 58: Overweight-Ratio 58 to 63: Extremely Overweight/Obese-Ratio over 63: Highly Obese

WOMEN: Ratio less than 35: Abnormally Slim to Underweight-Ratio 35 - 42: Extremely Slim-Ratio 42 to 46: Slender and Healthy-Ratio 46 to 49: Healthy, Normal Weight-Ratio 49 to 54: Overweight Ratio 54 to 58: Seriously Overweight-Ratio over 58: Highly Obese

4. Sagittal Abdominal Diameter

For persons of normal BMI, SAD should be under 25 centimeters.

A multidisciplinary approach …

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Physical Therapy

Behaviour Modification

Medical Therapy

Surgery

Dietary Management

… can identify the different factors and engage a program that leads to necessary reduction in weight:

Medical therapy

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Assessing Medication Efficacy and Safety

Effective Ineffective

Loss of ≥5% body weight at 3 months and medication is safe/tolerated

Loss of <5% body weight at 3 months or safety or tolerability issue with medication

Continue medication

Discontinue medication Seek alternate medication or refer for alternative therapy

Source: Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015.100(2):342–362.

Nut intervention goals

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• Set clear goals with a realistic timescale.

• Start reducing 5-10% from actual body weight

• Address individual needs based on Age, Height, Weight, Medical history, Cultural, Religious, and preferences….

• Re- evaluate the nutrition intervention.

Set clear goals with a realistic timescale

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START REDUCING 5-10% FROM ACTUAL BODY WEIGHT

• 5-10 percent weight-loss can result in a five point increase in HDL cholesterol.

• Was shown to decrease TG by an average of 40mg/dl.

• Both Systolic/ Diastolic decrease by 5mmHg

• Has effect with diabetes by improve A1C, and Insulin Resistance

• Sleep Apnea

Address individual needs based on Age, Height, Weight, Medical history, Cultural, Religious, and preferences….

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Energy requirements based on body weight and activity level

In patients who are not catabolic, energy requirements based on activity level are often quite acurate. However, a major limitation of this system is the absence of a precise definition of overweight, normal weight, and underweight, as well as activity level.

Energy requirements based on body weight and activity level

Age Energy needs, kcal/lb Energy needs, kcal/kg

0-6 months 49 108

6-12 months > 45 > 98

1-10 years 45 to 32* 100 to 70*

Females 11-14 years 21 47

15-18 years 18 40

Males 11-14 years 25 55

15-18 years 20 45

* Gradual decline with age

Dietary management

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• A Healthy Eating Plan within your requirements gives your body the nutrients it needs every day/ Emphasizes fruits, vegetables, whole grains, and fat-free or low-fat milk and milk products Includes lean meats, poultry, fish, beans, eggs, and nuts Is low in saturated fats, trans fat, cholesterol, salt (sodium), and added sugars.

• Controls portion sizes: Learn the difference between a portion and a serving and how to keep portions reasonable.

• Educate the patient about the smart substitutions to reduce sodium, saturated fat and added sugar.

• Eat regular meals & Don't let yourself get too hungry. This can help you to burn calories at a faster rate and avoid becoming too hungry.

• The different studies shown : How we can support increase metabolic rate by consuming some kind of foods ?

Conclusion

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The evidence demonstrates that the majority of people

who lose weight regain much than of that weight over a period of

One to Five years in the absence of continued intervention.

Any nutritionally balanced diet can be recommended … but the focus should be on adherence to a diet that is individualized for medical and metabolic conditions and ease of long-term maintenance and adherence.

Redustim

technology

Dr Daniel GREFF PhD BioChemistry

PARIS - France


The progressive destocking of lipids in excesses situated at the abdominal level

Our target

pull a decrease of the waist measurement so reduces the “health risks” connected to the metabolic syndrom

5 critères d’évaluation du syndrome métabolique ReduStim

spreads in the contact of the abdominal skin level and to the global physical level …

Frequency 50 Hz

Our solution

… a low frequency alternating magnetic field oscillating from o to 4 Gauss.

The magnetic field targets muscle cells by activation of Ca++ ATPases of the sarcoplasmic reticulum (calcium pump)

and induces lipolysis of fat stored around the muscles.

5 critères d’évaluation du syndrome métabolique • Several international studies have demonstrated stimulation of ATPase membranes

associated with calcium in the presence of weak alternating magnetic fields, less than 5 Gauss (corresponding to those of REDUSTIM), at low frequencies from 40 to 60 Hz (50 Hz for REDUSTIM).

• The Ca++ ATPase enzymes are localized in the membrane of the sarcoplasmic reticulum of muscle cells where they account for 90% in weight of total membrane proteins.

• Sarcoplasmic reticulum stores calcium and the rapid flow of these ions from the reticulum to the sarcoplasm (cytoplasm of muscle fibers) causes muscle contraction.

• The magnetic stimulation of the Ca++ ions that causes an increase in the activity of these ATPase automatically entails stimulation of lipolysis of stored fat around the muscles, without additional effort consumption.

• REDUSTIM therefore carries some of the energy expenditure cycle, as if a physical activity was conducted.

Our scientific basis


• Identification by DNA chip technology of the potential effects of 12 ReduStim sessions on gene expression in periphal blood of 11 individuals.

• The device has shown to induce a significant response, positively modulating the expression of 89 genes in all the individuals in 73% of cases and in parallel to the reduction of their waist circumferences.

Our experimental proof

5 critères d’évaluation du syndrome métabolique Activation of Ca++ ATPases

located in the membranes of the sarcoplasmic reticulum of muscle cells by the alternating magnetic field low frequency.

Stimulation of the muscular contraction of smooth and skeletal muscles.

Leading a consumption of ATP energy brought by a progressive destockage

of fat stored.



MUSCULAR CELL (MYOCYTE)

ENERGY

Destocking lipids

Lipolysis

MYOFIBRILLE

CONTRACTED MUSCLE

RELAXED MUSCLE

SARCOPLASMIC RETICULUM

Sarcoplasmic reticulum Sarcolemma

Mitochondrion

Nucleus

T-tubule

Myosin

Actin

Myosin Actin


Conclusion

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The description of these various stages allows to release an exclusive mode

of action of the low frequency alternating magnetic fields.

The reduction of the excess of fat mass whether it is of abdominal or physical

nature, is obtained by a natural biological stimulation of the lipolysis and not by

an invasive and destructive process, without any side effect.

It is the reason why we use the term of "BIOMAGNETIC FIELD"

to define our technology.


The progressive fat destockage in excesses located

at the abdominal level.

pull a decrease of the waist measurement reducing the

"health risks" connected to the metabolic syndrom.


Non-invasive, non-aggressive and totaly painless treatment ( 50 Hertz)


BIOMAGNETIC FIELDS

REDUSTIM

Non-ionising Ionising

Low induced

currents

Strong induced

currents

Electrical

excitation

Rupture of

molecular bonds

102 104 106 108 1010 1012 1014 1016 1018 1020

Radio Microwave Infrared Ultraviolet X-Ray

TV Cell phone UV lamp

Hz Frequency

Medical

X-ray

FM

Radio

AM

Radio

Electric

heaters

Home Power

lines

Our technology

Redustim, 100% hands-free medical device

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ReduStim guarantees

visible results in

12 sessions and exists under 2

versions.

REDUSTIM BioMagnetic field + Micropression

REDUSTIM SP BioMagnetic field

Static protocol

Dynamic protocol

Static protocol

Static protocol

5 critères d’évaluation du syndrome métabolique Redustim BIOMAGNETIC

FIELD + MICROPRESSION

Redustim: Biomagnetic field + micropression

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ReduStim takes the form of a device linked to an integral bodysuit that covers a large part of the body, from the feet up to the solar plexus. Two arms straps complete the device to diffuse the BioMagnetic field for the aesthetic treatment of skin slackening in this area.

It combines 2 simultaneous actions :

1. A main action based on the emission of BioMagnetic field to stimulate the release of visceral fat.

2. A secondary action of controlled cutaneous micropressure (drainage), facilitating body drain and the elimination of toxins.

Recommended treatment for overweight patients: 12 x 30 min sessions (2 sessions a week).

Recommended treatment for obese persons: 15 x 45 min sessions (2 sessions a week).

Global management of overweight and abdominal obesity.

Infertility in obese persons.

Treatment of post-natal obesity. Metabolic syndrome as a factor of risk in cardiovascular diseases and strokes.

Complementary medical methods: cryotherapy, infrared, carboxytherapy, lasers...

Redustim: medical indications

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5 critères d’évaluation du syndrome métabolique Redustim SP, static protocol,

BIOMAGNETIC FIELD

5 critères d’évaluation du syndrome métabolique Redustim SP, dynamic protocol

BIOMAGNETIC FIELD


Dynamic protocol is preventing cardiovascular risks. This protocol can be used to optimise the results combining the session with cardio exercise.

REDUSTIM SP static protocol is realized with a patient spread on a treatment table. A protocol dedicated for people with reduced mobility and having difficulties to exercise. It can be supplemented with rolling massage, lymphatic drainage or with other targeted medical methods.

Redustim SP: 2 protocols

Recommended treatment for overweight patients: 12 x 30 min sessions (2 sessions a week).

Recommended treatment for obese persons: 15 x 45 min sessions (2 sessions a week).

Redustim SP: medical indications

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Global management of overweight and abdominal obesity.

Metabolic syndrome as a factor of risk in cardiovascular diseases and strokes.

Treatment of abdominal obesity in menopausal women.

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Clinical studies Dr Philippe BLANCHEMAISON

Angiologist – Phlebologist PARIS - France

• A pivotal DNA chip study in 2009 proved the technology to modulate intracellular Ca++ (Dr Benech).

• A double-blind clinical trial was meanwhile sponsored in the metabolic syndrom indication (Dr Courie and Benichou, 2010) with positive results.

• A clinical trial was sponsored in an indication suggested by the study, infertility (Pr Frydman, 2011) with positive results.

• The visceral fat effects were confirmed in a scanner imaging study (Dr Nouira and Carpentier, 2013).

Strong scientific background

A clinically recognized therapy supported by 10 scientific and clinical studies

1998: Dr. Fargeon (Paris – France) – sample of 42 female patients

2003: Dr. Karray (Paris – France) – sample of 203 female patients

2004: Dr. Cheibi (Tunis – Tunisia) – sample of 21 female patients

2006: Dr. Fargeon (Paris – France) – sample of 23 patients

2007: Dr. Pavie (Paris – France) – sample of 36 female patients

2008: Dr. Beilin (Paris – France) – sample of 22 female patients

1 pivotal DNA chips study

Scientific and Clinical studies

1

2

3

4

5

6

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7 2009: Dr Philippe Benech (Prediguard) : “DNA chips” based predictive study on the physio-biological mode of action of Redustim

3 additionnal studies on BioMagnetic Field impact on health

2010: Dr Rodi Courie (Inserm U939 – Hospital Pitié Salpêtrière) – Dr Florence Benichoux): randomized, double-blind clinical study. Average waist loss of 6.1 cm after 12 sessions of Redustim

2011: Dr V. Gallot, Pr René Frydman, Pr R. Fanchin (Hôpital Antoine Béclère – Clamart): clinical study on potential benefit of BioMagnetic stimulation on Fertility: 55% pregnancy rate after 12 sessions of BMS (vs 23,7% in average) 2013: Dr Habib Nouira et Dr Bernadette Carpentier: scanner imaging study: impact on the body fat content after 12 sessions

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9

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347 patients observed in 6 different medically controlled studies

Waistline reduction of more than 1 size; no side-effect

1998 : Dr. Fargeon (Paris – France) First study lead by Dr. Fargeon in 1998 to test effectiveness of Bodysculptor® on 42 overweight female patients. Results after 12

weeks showed an average decrease of the waist circumference by 6,1cm.

2003 : Dr. Karray (Paris – France) Study lead by Dr Karray in 2003 on 203 female patients confirmed significant results on weight loss (average loss of 5,4 kg) and

waist circumference reduction: average loss of 10,5 cm.

2004 : Dr. Cheibi (Tunis – Tunisia) Study lead by Dr Cheibi in 2004 on 21 female patients proved a reduction of more than 1 size for 100% of the patients after 12

sessions of 30 minutes and vibrating plate exercise (20 minutes).

Study 2006 : Dr. Fargeon (Paris – France)

4 Study lead by Dr Fargeon in 2006 on 23 female patients proved a reduction of more than 1 size for 100% of the patients after 12

sessions of 30 minutes and mechanical drainage (20 minutes).

2007 : Dr. Pavie (Paris – France) Study lead by Dr Pavie in 2007 on 36 female patients proved a reduction of more than 1 size for 100% of the patients after 12

sessions of 30 minutes with micro-pressure stimulation.

2008 : Dr. Beilin (Paris – France) Study lead by Dr Beilin in 2008 on 22 female patients proved a reduction of more than 1 size for 100% of the patients after 12

sessions of 30 minutes with micro-pression stimulation (3 sessions per week).

Study

1

Study

2

Study

3

Study

5

Study

6

Study

4

347 patients observed in 6 medical studies

Randomized, double-blind clinical study

Average reduction in waist measurement

Results in centimeters after 12 sessions

P<0,01*

* The significance level of the difference is high: study carried out using Student’s test on matched series.

Evaluation of average centimetre drop in waist size in 28 patients with abdominal obesity after 12 sessions of ReduStim: -6.1 cm. The other 4 metabolic syndrome criteria remain unchanged.

The liver transaminase rate has reduced: • ALAT: a 23% reduction • ASAT: a 13% reduction The circulating fatty acids that are released are not stored in the liver: on the contrary, the BioMagnetic field helps to detoxify it.

-6,07 Placebo

-1,81

Dr Rodi Courie (Inserm U939 – Hospital Pitié Salpêtrière) – Dr Florence Benichoux) - 2010

Study

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Primary clinical result:

After a 12-session cure with Redustim®, average decrease in waist circumference by 6,1 cm in patients with abdominal obesity vs -1,8 with

placebo.

The study demonstrated that the waist circumference decreased whereas the 4 other criteria of the metabolic syndrome haven’t been significantly modified

(which is a positive sign regarding the biological side effects of the medical device).

Redustim® has a positive action on lipids accumulated abnormally around

visceral and muscles (mainly on the abdominal zone).

The results of the IVF in obese and overweight infertile female patients, after a reduction of their waist circumference following 12 sessions of Redustim®. 38 female patients candidate for an IVF (first or second attempt) with a body mass index (BMI) > 25 Kg/m2 has benefitted from 12 sessions of 30 minutes Redustim® (with 2 sessions per week) during the 6 weeks preceding the ovarian stimulation for the IVF, without any modification of the established clinical protocol.

Dr V. Gallot, Pr René Frydman, Pr R. Fanchin (Hôpital Antoine Béclère – Clamart) - 2011

Study

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Study

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Study on fertility of overweight female patients


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z

After a 12-session cure with Redustim®, the clinical pregnancy rates after IVF,

in an obese infertile amount to 55.55%.

Classification BMI No. of IV

Fertilization patients

No. of pregnancies

Pregnancy rate

Overweight 25 to 29,9 11 4 36,36% Class 1 obese 30 to 34,9 13 6 46,15% Class 2 obese 35 to 39,9 8 5 62,50% Class 3 obese (morbid obesity)

40 over 6 4 66,67%

Total (all types) 25 to 40 over 38 19 50,00%

Total (obese only) 30 to 40 over 27 15 55,55%

Pregnancy rate in vitro fertilization as a function of BMI

62,5%

46,15%

36,36%

66,67%

Overweight Class 1 obese

Class 2 obese

Class 3 obese

Dr Habib Nouira et Dr Bernadette Carpentier - 2013

The study using ReduStim SP in static mode quantified and compared the impact of the device after 12 sessions before and after treatment on subcutaneous and visceral body fat around the navel, using Scanner view without preparation (Toshiba Aquilion 16). This present study conducted on 20 volunteers (12 females + 8 males) with an average weight of 95.30 kg and an average BMI of 30.90 has shown: -An average reduction of 5.45 kg in weight and 6% in BMI -An average reduction of 7 cm in waist circumference, 8.2% in visceral body fat and 4.1% in sub-cutaneous body fat -An average reduction in transaminase ASAT and ALAT of 17.4% and 18% respectively

Scanner imaging study Study

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Scanner imaging study

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BEFORE

The technology proved to target in priority the visceral or “bad” fat and to a lesser extent

the subcutaneous fat (that happens to be an aesthetic concern but associated with a

lower morbidity). Released fatty acids are proved to be burnt by the organism and not

stocked in the liver.

AFTER

Redustim results and testimonies

Dr Philippe BLANCHEMAISON Angiologist – Phlebologist

PARIS - France

BEFORE AFTER BEFORE AFTER

BEFORE AFTER BEFORE AFTER

Before / after 12 Redustim sessions

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Doctors equipped testimonials

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Doctors equipped testimonials

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Professional division portfolio: a Compelling Value Proposal for both

Customers and Practitioners

Our group has now equipped 2500 professional sites around the world. Each of them undergo 2 x 30’ sessions per day on average or circa 600 per year (50 customers). Over 125,000 customers will use the technology this year and

more than 1,500,000 sessions will be managed. In cumulative terms it means over 15 billion sessions since 10 years. With not one single serious side-effect reported, meaning a side-effect having led to an interruption of the protocol.

Efficacy on body shaping and good for health The only device that works on visceral/intra-abdominal fat

None-invasive and Safe with no side effects

No pain or risk of negative metabolic interaction

Affordable pricing

The attractive economics of the devices allow for average treatment prices

Value Proposal for the customer Value Proposal for the practitioner

Compelling risk/efficacy couple Harmless, painful

with no side effects (15 years “pharmaco-vigilance”)

Really hand-free A session requires less than

10mn manipulation by the operator

Attractive Economics Attractive ROI and short payback

(<1 year for more than 90% of the spas that were equipped) No consumables or hidden costs

Devices values

A medical device that optimises global management of overweight or obese patients.

A device 100% Made in France with scientifically and clinically proven results.

A 100% hands-free treatment.

A device that improves the profitability of your medical center.

A device for recruiting new patients and also building loyalty

among your existing patients.

An alternative to major surgery (painless, non-invasive method).

A space saving device that does not require a dedicated cubicle.

Very few contraindications.

Devices strengths

abdominal obesity : the risks factors .redustim, a medical device solution

Health & Medicine