Device for preventing tumor recurrence

Abstract

A wearable device (1) for treating cancer cells by mechanical stimulation of a patient's surface tissue, in particular skin, subcutaneous tissue or mammary gland, wherein the device (1) comprises: a support element (2) applicable to the patient's tissue; and stimulation and control means (3) connected to the support element (2) wherein the stimulation and control means (3) comprise: at least one actuator (4) for delivering the mechanical stimulation at at least one stimulation point (5); at least one sensor (6) for detecting a physical property at the tissue of the patient to be treated and for generating a corresponding sensor signal; and a control unit (7) connected to the actuator (4) and to the sensor (6), the control unit (7) for regulating the movement of the actuator (4) by a control signal in dependence on said at least one sensor signal, in which the mechanical stimulation is transmitted by the actuator (4) to the stimulation point (5) in order to deform the tissue to be treated in dependence on a periodic trend, especially the contraction and relaxation of the tissue.

Description

Technical Field

[0001] This invention relates to a wearable device for treating cancer cells by mechanically stimulating the surface tissues of a patient, particularly the skin, subcutaneous tissue, or breast. Existing technology

[0002] Cancer is the second leading cause of death worldwide, imposing a tremendous physical, emotional, and economic burden on patients, their families, communities, and healthcare systems. To date, the control and prevention of localized cancer recurrence remains one of the major unmet needs. Recurrence typically precedes metastatic spread and negatively impacts long-term survival and quality of life. Current therapies for cancer treatment and recurrence prevention have significant side effects and are primarily based on systemic treatment of metastatic disease, which often fails to achieve long-term cure at this stage. For decades, chemotherapy has been the primary effective treatment for cancer. However, its effectiveness remains limited by off-target toxicity and the selection of drug-resistant cancer cells. In recent years, immunotherapy and targeted therapy have gained attention due to their higher specificity for cancer cells. These approaches have shown promise in clinical trials for various cancers and can be used alone or in combination with traditional drugs. However, not all patients respond positively to these therapies, and they are often accompanied by significant toxicity, particularly to the cardiovascular system. Therefore, localized recurrence remains an unmet medical need. Currently, there are no solutions for locally controlling cancer recurrence and spread.

[0003] Inspired by evidence of tumor nonproliferation in the human and mouse hearts, medical biology research has shifted its focus in exploring the causes of tumor suppression towards biomechanical interactions.

[0004] It is known that cancer progression is influenced by mechanical stimulation. Changes in tissue stiffness and density are important stimuli of tumor progression and are often utilized in cancer diagnosis through palpation and imaging. However, although biomechanical interactions have revealed how mechanical properties (stiffness, elasticity) affect cancer cell growth, little is known about the actual effects of mechanical stimulation (pressure, tension).

[0005] The mammalian heart is rarely affected by cancer, possibly due to the same mechanisms that inhibit cardiac regeneration. Primary myocardial tumors are extremely rare, with an incidence of approximately 0.0017%. Cardiac metastases typically involve the pericardium or large blood vessels, rather than the myocardium. Furthermore, ectopic cancer cells implanted in the heart form small, avascular tumors, suggesting that the cardiac environment inhibits the growth of both endothelial cells and cancer cells. Simultaneously, it is known that the mammalian heart rapidly loses its regenerative capacity after birth. Specifically, mechanisms leading to the termination of proliferative potential of cardiomyocytes (including cardiomyocytes (CMS) and cardiac endothelial cells) after birth can be identified. Mechanical stimulation is emerging as a key factor, particularly in patients with implanted left ventricular assist devices (LVADs), where mechanical unloading of the heart occurs.

[0006] Existing technologies have disclosed devices and methods for treating cancer cells through mechanical stimulation. For example, EP 3 312 506A1 discloses a device for treating gastrointestinal tumors through tissue mechanical stimulation, and WO 2020 / 223242 A1 discloses a method for treating cancer cells by inducing cell death (apoptosis) through external mechanical stimulation (pneumatic or hydraulic) of specific frequencies and intensities. However, in many cases, these solutions involve internal treatment, thus requiring surgical intervention for the patient. Furthermore, even external treatments typically require large, expensive equipment that can only be operated by professionals. In such cases, patients must travel to specialized medical facilities for treatment.

[0007] Therefore, the object of the present invention is to provide a device for treating cancer cells that partially or completely overcomes the deficiencies of the prior art. Specifically, the object of the present invention is to obtain an effective, easy-to-use device that does not require the patient to remain in a medical facility during treatment. Summary of the Invention

[0008] The above objectives are achieved by the wearable device described in the claims at the end of this disclosure.

[0009] In one aspect of the invention, a wearable device is provided for treating cancer cells by mechanically stimulating a patient's surface tissue (particularly skin, subcutaneous tissue, or breast tissue). The device includes a support element applicable to the patient's tissue and stimulation and control means connected to the support element, wherein the stimulation and control means includes:

[0010] - At least one actuator for delivering the mechanical stimulus at at least one stimulation point;

[0011] - At least one sensor for detecting physical properties at a site in the tissue of a patient to be treated and for generating a corresponding sensor signal; and

[0012] - A control unit connected to the actuator and the sensor, the control unit being used to adjust the activity of the actuator via a control signal based on at least the sensor signal.

[0013] The mechanical stimulation is transmitted from the actuator to the stimulation point, thereby determining the deformation of the tissue to be treated, especially the contraction and relaxation of the tissue, based on periodic trends.

[0014] It should be noted that the deformation of the stimulation point (and consequently the deformation of the tissue to be treated) can be compared to the periodic function of alternating compression and relaxation of the tissue being treated. Thus, through a mechanically activated biological mechanism, the tissue forms a dynamic environment that is extremely unfavorable to tumor proliferation.

[0015] For example, this periodic trend can be compared to the cardiac cycle, meaning that the force and deformation of the mechanical stimulation applied by the device are comparable to the force and deformation experienced by the heart. However, other periodic trends different from the cardiac cycle can also be advantageously used to achieve the same purpose.

[0016] In addition, it should be noted that the tissue to be treated is subjected to mechanical stimulation, rather than stimulation by electrical discharge as is the case with muscle stimulators known in the prior art.

[0017] These and other aspects of the invention will become more apparent from the following description of some preferred embodiments disclosed.

[0018] Figure 1 A schematic diagram of a device for treating cancer cells, based on an example, is shown.

[0019] Figure 2A -B illustrates two possible implementations of the device, where the support element is a strap (A) or clothing (B).

[0020] Figure 3 It schematically shows the following based on Figure 2A The type of stimulation for the example device.

[0021] Figure 4 A flowchart of a closed-loop control based on an example is shown.

[0022] Figure 1 A device 1 for treating cancer cells 10 by mechanical stimulation is shown. Specifically, the device 1 is capable of locally reproducing or simulating mechanical stimulation characterized by the cardiac cycle on the skin or subcutaneous tissue, for the purpose of preventing recurrence of tumors that can be reached by tactile stimulation (such as melanoma, breast tumors, etc.).

[0023] Advantageously, the device 1 is wearable and includes a support element 2 that can be applied to the patient's tissues. For example, the support element 2 can be made of textile material and take the form of a strap or clothing (bra, vest, T-shirt, stockings, etc.). The support element 2 can, of course, be made of various materials, such as natural or synthetic fibers. Furthermore, the support element 2 can be made of an elastic material to facilitate contact with the patient's skin tissue. The support element 2 can also be made wholly or partially of plastic or silicone.

[0024] To generate mechanical stimulation and modulate the pulses applied to the patient's tissue, the device 1 further includes a stimulation and control device 3. This device 3 is connected to the support element 2 such that the stimulation generated by the device 3 can be transmitted to the support element 2. Advantageously, the stimulation and control device 3 is removably connected to the support element 2. Alternatively, the stimulation and control device 3 may be integrated into the support element 2.

[0025] The stimulation and control device 3 includes one or more sensors 6 for detecting the physical properties of patient tissue. The sensor 6 is used to detect at least one physical property among pressure, temperature, stiffness, local deformation, and / or optical properties. However, other physical properties may also be considered. For example, the sensor 6 may be a force sensor for measuring the force (i.e., pressure) applied to a tissue area. However, the device 3 may include different sensors 6, such as sensors for detecting temperature or other parameters used to monitor the state of patient tissue (especially cancer cells 10). Depending on the type of sensor present, the sensor 6 generates a corresponding sensor signal containing information related to the measured physical property. The sensor 6 may be, for example, a durometer for measuring tissue stiffness, an optical sensor for measuring tissue optical properties, or a strain gauge for measuring local tissue strain.

[0026] In order to generate mechanical stimulation acting on the patient's tissues, the stimulation and control device 3 further includes one or more actuators 4. Specifically, the actuators 4 are used to deliver mechanical stimulation at at least one stimulation point 5.

[0027] The stimulation and control device 3 further includes a control unit 7. This control unit is connected to the sensor 6 to receive sensor signals and to the actuator 4 to regulate the activity of the actuator 4 via a control signal. The control signal is generated based on the sensor signal. However, the control signal may also be generated based on other predefined information or data present in the control unit 7.

[0028] The various components of the device 1 can be powered by the battery 9. This battery is connected at least to the control unit 7, but may also be connected to the sensor 6 and the actuator 4. Advantageously, the battery 9 is a rechargeable battery. It should be noted that the device 1 can be powered by alternative means that do not require the battery 9, such as utilizing solar energy and / or kinetic energy generated by the patient.

[0029] It should be noted that the mechanical stimulation transmitted from the actuator 4 to the stimulation point 5 causes deformation of the tissue to be treated, simulating a cardiac cycle. Specifically, this tissue deformation can manifest as the tissue's own contraction and relaxation, similar to the contraction and relaxation of myocardial tissue during cardiac activity. In other words, the control unit 7 is programmed and thus configured to send control signals to the actuator 4, causing the actuator 4 to reproduce a heart-beat-like stimulation at the diseased tissue (stimulation point 5), thereby locally simulating the forces and pressures exerted on the heart wall and their deformation. The deformation of the tissue to be treated is a result of the movement of the support element 2 at the stimulation point 5. Specifically, the support element 2 is configured to locally expand, globally contract, or achieve a combination of expansion and contraction at the stimulation point 5 according to a periodic trend. To achieve this expansion and contraction, the support element 2 is made of a deformable material. For example, the support element 2 may include portions capable of changing its volume. For example, this can be achieved through a pneumatic system with airflow within the chamber, a hydraulic system with fluidflow within the chamber, a piezoelectric system, an external deformable element, or any system capable of causing the support element 2 to change its volume periodically.

[0030] As mentioned earlier, this cyclical trend is similar to a typical cardiac cycle. The cardiac cycle begins with sinus rhythm, where electrical waves generated by the sinoatrial node propagate through the conduction tissues, stimulating the contraction of the heart chambers (first the atria, then the ventricles), pumping blood out of the heart.

[0031] In one example, the mechanical stimulation transmitted from the actuator (4) to the stimulation point (5) produces a g of greater than 120 mmHg (i.e., approximately 120 mmHg) in the tissue to be treated (i.e., at the stimulation point (5)). (the maximum pressure).

[0032] To simulate the cardiac cycle, actuator 4 transmits stimulation pressure to stimulation point 5. and diastolic pressure The stimulus pressure Greater than this diastolic pressure In other words, in the periodic expansion and contraction of the support element 2, the actuator 4 transmits different pressures to the stimulation point 5 depending on whether it is in the expansion or contraction phase. From a pressure value (e.g., stimulation pressure) To another pressure value (e.g., diastolic pressure) The transitions can occur continuously or follow a trend at discrete levels.

[0033] During the stimulation phase, actuator 4 transmits maximum stimulation pressure to stimulation point 5. Its value can range from 125 mmHg to 250 mmHg (125 mmHg < <250 mmHg). These values ​​correspond to the left ventricular pressure during systole and the intramural pressure during the same period. During diastole, the diastolic pressure at the stimulation point (5) is... Approximately 0 mmHg, but always less than 7 mmHg (0 mmHg < <7 mmHg), which corresponds to the left ventricular pressure during diastole in a healthy heart.

[0034] Alternatively or concurrently, the mechanical stimulation transmitted from actuator 4 to stimulation point 5 produces a maximum local volume deformation of at least 130 ml at stimulation point 5 (and consequently on the tissue to be treated). In this context, local volume deformation refers to the volume change of the stimulated tissue site between the compression and relaxation phases.

[0035] Alternatively, the mechanical stimulation transmitted from actuator 4 to stimulation point 5 produces a frequency greater than or equal to 0.05 Hz at stimulation point 5 (and thus on the tissue to be treated), particularly a frequency greater than or equal to 1 Hz, and even more particularly a frequency between 1 Hz (60 beats per minute, bpm) and 2 Hz (120 bpm), to simulate the heart rate of a healthy heart in both resting and stressed states. It should be noted that the frequency is not random, but varies according to a specific cycle (i.e., the cardiac cycle) as previously described.

[0036] In other words, to simulate the cardiac cycle of a healthy human heart, the wearable device 1 disclosed herein can transmit pressure at stimulation point 5 (and thus on the tissue to be treated) according to the above parameters. and diastolic pressure Mechanical stimulation that varies between these pressure values. In addition to these pressure values, the wearable device 1 described herein can deliver mechanical stimulation with frequencies having the aforementioned parameters. By combining these frequencies and pressure values, the cardiac cycle can be simulated more effectively.

[0037] In addition to these pressure and frequency values, the wearable device 1 described herein can deliver mechanical stimulation with volume changes exhibiting the aforementioned parameters. By combining these frequency, pressure, and volume change values, the cardiac cycle can be simulated more effectively.

[0038] It should be noted that the normal duration of a cardiac cycle at rest is approximately 0.8 seconds. Within this duration, one-third of the time is spent in systole (i.e., ventricular contraction), and two-thirds in diastole (i.e., ventricular relaxation).

[0039] Therefore, the actuator 4 of this disclosure is configured to apply a time-asymmetric stimulation curve. This means that during the mechanical stimulation applied by the actuator 4, the rising phase (e.g., contraction) and the falling phase (e.g., relaxation) of the cycle have different durations. In other words, the time taken from the initial state to the final state is different from the time taken to return from the final state to the initial state.

[0040] Specifically, the mechanical stimulation is transmitted from the actuator 4 to the stimulation point 5, causing the support element 2 to... Local expansion at the stimulation point, and over time The whole area contracted, among which Unlike ,For example .

[0041] It should be noted that the values ​​for maximum pressure, volumetric deformation, and frequency are consistent with the curves reported in the Wiggers diagram of a healthy heart.

[0042] The actuator 4 may include a force transmission system coupled to the stimulation point 5. Depending on the technology used to manufacture the stimulation and control device 3, the actuator 4 may be of different types.

[0043] In one example, at least one actuator 4 is a mechanical or electromechanical actuator, particularly a linear actuator or a servo motor. In this case, tendons, gears, and pulleys can transmit the motion activated by the motor and servo motor to the stimulation point 5, and then to the patient tissue, for example, acting directly on the tissue itself or indirectly on the support element 2.

[0044] Alternatively or concurrently, at least one actuator 4 is a pneumatic actuator, particularly comprising at least one air chamber connected to a pumping system and a valve. In this configuration, one or more air chambers undergo continuous expansion and compression cycles via an air transmission system connected to the pump and valve.

[0045] Alternatively or concurrently, at least one actuator 4 is a piezoelectric actuator, particularly comprising a piezoelectric material element coupled to a deformable mechanical element. In this case, the piezoelectric material can be integrated with the interface of the support element 2, and its volume can be changed when a current with appropriately modulated amplitude and frequency flows through it.

[0046] Alternatively or concurrently, at least one actuator 4 is a shape memory polymer actuator, particularly comprising a thermoplastic polymer, thermoset polymer, or elastomeric polymer material. In this case, the shape memory polymer can change its stretched state, oscillating between one or more stable shapes due to external stimuli (such as heat), thereby ensuring the application of periodic mechanical forces locally.

[0047] In any case, the actuator 4 and / or the support element 2 may be made of a material with a hardness between 10 and 30 Shore 00 to effectively simulate the volumetric deformation during the systolic and diastolic phases of the cardiac cycle at the stimulation point 5.

[0048] Of course, other types of actuators 4 that can apply mechanical stimulation at the stimulation point 5 can also be used.

[0049] Figure 2A and Figure 2B Two wearable devices 1 for treating cancer cells 10 are shown. In one case ( Figure 2A The support element 2 is a textile or silicone band. Therefore, the device 1 can be worn on the melanoma 10 on the patient's arm. Figure 2A In the diagram, double arrows indicate the action of actuator 4 (not shown) on the band-type support element 2. The action of actuator 4 can cause the band to contract or relax, resulting in deformation of the support element 2 and subsequently the skin tissue at the stimulation point 5 or cancer cell 10. The action of actuator 4 is controlled by control unit 7 so that the deformation changes over time, similar to heart contractions, for example, based on the aforementioned pressure, frequency, and / or volume change parameters.

[0050] In another case ( Figure 2B The support element 2 is an undergarment (e.g., a bra). Therefore, the device 1 can be worn, and the stimulation and control device 3 is located at the cancer cell 10 (e.g., the left breast). Advantageously, the stimulation and control device 3 can be removed from the support element 2 and can be conveniently placed in another area of ​​the support element 2 (e.g., another area of ​​the right or left breast).

[0051] Stimulation point 5 is the effective contact point between device 1 and the diseased tissue to be mechanically stimulated. In one example, at least one stimulation point 5 is integrally formed with support element 2. For example, stimulation point 5 may be part of support element 2. In this case, the action of actuator 4 is transmitted to support element 2 such that stimulation point 5 is located in the area of ​​support element 2 in contact with patient tissue. In other words, the transmission of mechanical stimulation from actuator 4 to stimulation point 5 is indirect. For example, two or more points of support element 2 may be pulled in opposite directions, thereby generating pressure in one area of ​​support element 2 (i.e., stimulation point 5) through the contraction of support element 2 (e.g., the contraction of a strap around the patient's arm).

[0052] Alternatively or concurrently, at least one stimulation point 5 may be integrally formed with the stimulation and control device 3. For example, the stimulation point 5 may be part of the actuator 4. In this case, the action of the actuator 4 is directly transmitted to the stimulation point 5 in contact with the patient tissue. In the latter case, the device 1 may further include a thrust body 8 connected to the actuator 4, wherein the thrust body 8 is rigid or deformable. Figure 1(Seen as dashed elements in the diagram). The thrust body is configured to apply localized forces and pressures through its own expansion or compression. The thrust body 8 can be, for example, a pin or a ball, serving as a transmission system for mechanical stimulation. The thrust body can be integrated with or separated from the actuator 4.

[0053] refer to Figure 3 Considering Figure 2A The configuration of device 1 (i.e., the band worn around the patient's arm) shows three different mechanical stimulation modes of cancer cells 10.

[0054] exist Figure 3 In example (i), mechanical stimulation is achieved through the overall contraction of support element 2. For example, the two strips of the band are pulled in the same direction. In this case, stimulation is achieved through the periodic contraction of support element 2, compressing and relaxing the tissue to be treated in a periodic, broad, and overall manner. Specifically, the contraction of the band produces compression on the forearm (e.g., the site of melanoma). Although the stimulation is broad, controlled closed-loop application occurs below the stimulation device 3, which serves as an element capable of measuring the mechanical state of the tissue.

[0055] exist Figure 3 In example (ii), mechanical stimulation is achieved through the local expansion of the support element 2 at the stimulation point 5. For example, the thrust body 8 can be pressed against the stimulation point 5 by the action of the actuator 4. In this case, the pneumatic device with the thrust body 8 can apply local pressure to the tissue to be treated by the expansion of the deformable membrane. This is indicated by the arrow extending from the thrust body 8. The expansion of the thrust body 8 also transmits stimulation to the tissue in contact with the support element 2. In this case, the control loop also closes only around the stimulation device 3, specifically around the thrust body 8.

[0056] exist Figure 3 In example (iii), mechanical stimulation is achieved through a combination of contraction in example (i) and expansion in example (ii). In this case, the two stimulation methods described above (i.e., diffusion stimulation through support 2 and local stimulation through thrust body 8) are combined.

[0057] In other words, stimulation is applied through stimulation point 5 (e.g., a dedicated thruster or the band itself), which is activated by a motor controlled, for example, by a control unit 7, which combines information provided by measuring sensor 6 with its internal programming (suitable for simulating a heartbeat). The resulting stimulation is then applied to the patient's skin through the contraction of the band, the expansion of the stimulation point, or a combination thereof.

[0058] In one example, actuator 4, sensor 6, and control unit 7 constitute a closed-loop control system. Specifically, the closed-loop control system is configured to perform the following operations: measuring a first force applied to patient tissue via sensor 6; generating a control signal based on at least the measurement by control unit 7; activating actuator 4 via the control signal; and applying a second force different from the first force to the patient tissue. The steps of this control process 100 are as follows: Figure 4 As shown.

[0059] In other words, the operation of the stimulus and control device 3 involves a continuous cycle of force measurement, force calculation, and application, following the model below:

[0060] First, sensor 6 measures the force applied to the skin (S101). Control unit 7 generates a control signal based on the information provided by sensor 6 and a force reference value known in its programming (S102). The control signal activates actuator 4 (S103). Actuator 4 generates deformation and / or force, which is transmitted to stimulation point 5 via a transmission system (S104). The closed-loop control system is a closed measurement-control-execution loop around the patient's skin.

[0061] The design of the aforementioned devices in terms of materials, delivery, and implementation conforms to the three paradigms of wearable robotics technology: i) safety; ii) convenience; and iii) ease of use.

[0062] Those skilled in the art can make various further modifications and variations to the above-described device to meet additional and temporary needs, and all such modifications and variations are included within the scope of protection of the invention as defined by the appended claims.

Claims

1. A wearable device (1) for treating cancer cells by mechanical stimulation of a patient's surface tissue (particularly skin, subcutaneous tissue, or breast tissue), wherein the device (1) comprises: Supporting elements (2) that can be applied to the patient's tissues; as well as A stimulation and control device (3) connected to the support element (2), wherein the stimulation and control device (3) comprises: - At least one actuator (4) for delivering the mechanical stimulus at at least one stimulation point (5); - At least one sensor (6), said at least one sensor (6) being used to detect at least one physical property of the tissue of the patient to be treated, including pressure, temperature, stiffness, local deformation, and / or optical properties, and to generate a corresponding sensor signal; and - A control unit (7) connected to the actuator (4) and the sensor (6), the control unit (7) being used to adjust the activity of the actuator (4) by means of a control signal based on at least the sensor signal. The mechanical stimulation is transmitted to the stimulation point (5) by the actuator (4), and the support element (2) is configured to locally relax, contract as a whole, or achieve a combination of relaxation and contraction at the stimulation point (5) according to a periodic trend.

2. The device (1) as described in claim 1, characterized in that, The mechanical stimulation transmitted from the actuator (4) to the stimulation point (5) is generated at the stimulation point (5): a. Maximum pressure greater than 120 mmHg; and / or b. Maximum local volume deformation of at least 130 ml; and / or c. A frequency greater than or equal to 1 Hz.

3. The device (1) as described in any of the preceding claims, characterized in that, The at least one stimulation point (5) is integrally formed with the stimulation and control device (3).

4. The device (1) as described in claim 3, characterized in that, The device (1) further includes a thrust body (8) connected to the actuator (4), wherein the thrust body (8) is rigid or deformable.

5. The device (1) as claimed in any of the preceding claims, characterized in that, The at least one stimulation point (5) is integrally formed with the support element (2).

6. The device (1) as claimed in any of the preceding claims, characterized in that, The at least one actuator (4) is a mechanical or electromechanical actuator, especially a linear actuator or a servo motor.

7. The device (1) as claimed in any of the preceding claims, characterized in that, The at least one actuator (4) is a pneumatic actuator, particularly including at least one air chamber connected to a pumping system and a valve.

8. The device (1) as claimed in any of the preceding claims, characterized in that, The at least one actuator (4) is a piezoelectric actuator, particularly comprising a piezoelectric material element coupled to a deformable mechanical element.

9. The device (1) as claimed in any of the preceding claims, characterized in that, The at least one actuator (4) is a memory polymer actuator, particularly including thermoplastic polymer, thermosetting polymer or elastomeric polymer materials.

10. The device (1) as claimed in any of the preceding claims, characterized in that, The actuator (4), the sensor (6), and the control unit (7) constitute a closed-loop control system, wherein the closed-loop control system is specifically configured to perform the following operations: measuring a first force applied to the patient's tissue by the sensor (6); generating a control signal based on at least the measurement by the control unit (7); activating the actuator (4) by the control signal; and applying a second force different from the first force to the patient's tissue.

11. The device (1) as claimed in any of the preceding claims, characterized in that, It further includes at least a battery (9) connected to the control unit (7), wherein the battery (9) is in particular a rechargeable battery.

12. The device (1) as claimed in any of the preceding claims, characterized in that, The support element (2) is a strap or clothing.

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